Share my recent Pap-HPV research results with you

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楼主发表于 2009-06-12 22:01|举报|关注(0)
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1 楼发表于2009-06-27 19:46:00举报|引用
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Thank laurelshihxbl for 翻译 of the AGC abstract:

verification bias:

Example: We perform Pap screening test with biopsy follow up. 10% women with LSIL Pap have or develope CIN 2/3. Then we conclude the risk of women with LSIL Pap for CIN 2/3 is 10%. However, women with normal Pap also can develop CIN 2/3 in study period. Rare studies can include a control group----to do the cervical biopsy for the women with negative Pap. True risk for LSIL-CIN 2/3 may be less than 10%.

This is called verification bias.

In fact the only study in which the control group of women with negative Pap had colposcopic examination was performed in Shanxi, China several years ago. This is called verification bias-adjusted.

In our AGC study, we added the data about hysterctomy specimens. We calculated the AGC rate in all women with hysterectomy (cervical tissue were examined). This data avioided verification bias-----called verification bias- adjusted.

It is a very complicated concept. I am not sure if I explain it clearly.

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2 楼发表于2009-06-12 23:30:00举报|引用
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Above are my Pap-HPV research results in the past three years. Wish our young pathologists can also do some research and summarize you data based on your situation.

Thank you for reading,

cz

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3 楼发表于2009-06-12 23:26:00举报|引用
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2008 USCAP abstract (is working for paper)

Follow-up outcomes of cytological and histological abnormalities among women with negative computer-imaged liquid-based Pap and positive HPV DNA test results

C Zhao, RM Austin

Department of Pathology, Magee-Womens Hospital (MWH) of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

Background:

Limited data from the U.S. and overseas has been reported on the natural history of high risk(hr) HPV DNA positive women screened with negative conventional Pap smear results, but no reports have documented follow-up of cytology negative- HPV positive women routinely screened with newer methods of liquid-based cytology (LBC), computer-assisted screening, and HPV reflex or co-testing. The purpose of this study was to document the development of cytological and histological abnormalities among several hundred women who tested hrHPV DNA positive along with negative computer-imaged liquid-based Pap co-test results (DNAwithPap).

Design:

The computerized hospital records of MWH were searched for patients reported as negative on ThinPrep Imaging System (TIS)-imaged ThinPrep Pap tests (TPPT) who also had positive Hybrid Capture 2 (HC2) hrHPV DNAwithPap co-test results over a 30 month span between July 2005 and December 2007. Cytologic and histologic follow-up outcomes were analyzed.

Results:

During the study period 402 women with negative TPPT and concurrent positive HC2 hrHPV DNA test results had documented cytologic and/or histologic follow-up. Histologic follow-up included 111 women who underwent cervical biopsy with or without ECC and 39 who underwent ECC alone. The mean age was 41.6 years (15-84 years). The average follow-up period was 13 months, ranging from 1 to 35 months (mean 10.6 m). Follow-up results documented that 8 of 402 (2.0%) women had tissue diagnoses of intraepithelial neoplasia 2+, including, four CIN2, 2 CIN3, one VAIN3, and one case of AIS on biopsy and microinvasive endocervical adenocarcinoma on subsequent conization. CIN1 or LSIL were confirmed in 61 (15.2%) and 82 (20.4%) had follow-up ASC-US Pap test results without biopsy findings of CIN1+. All CIN 2+ and 50 of 61 CIN 1 lesions were diagnosed based on histology. The interval between positive HPV and negative TPPT findings and an initial diagnosis of CIN 2+ ranged from 1 month to 19 months (median 14 months).

Conclusion:

CIN3, often proposed as a surrogate for invasive cervical cancer in cervical screening trials, was detected on initial follow-up (average 13 months) in 2 of 402 women (0.5%) with negative computer-imaged TPPT and positive HPV co-test results. Inclusion of two additional cases of histologically detected CIN2, one VAIN3, and one case of AIS with microinvasive endocervical adenocarcinoma potentially alters the risk profile of this cohort of over 400 cytology negative HPV positive patients. Additional natural history studies are needed on cytology negative HPV positive women routinely screened with modern methods which are now prevalent in the U.S. The potential benefits of routinely combining LBC and HPV co-testing for enhanced detection of endocervical neoplasia deserves special study, given the limited reported success of screening in this area to date.

Table 1

Cytologic and histologic follow-up results among 402 women with positive HPV tests and negative Pap tests

Follow-up	No.	%
Negative	251	62.4
ASC-US	82	20.4
CIN 1/LSIL	61	15.2
CIN 2	4	1.0
CIN3	2	0.5
VAIN3/AIS	2	0.5

2008 USCAP abstract (is working for paper)

Follow-up outcomes of cytological and histological abnormalities among women with negative computer-imaged liquid-based Pap and positive HPV DNA test results

C Zhao, RM Austin

Department of Pathology, Magee-Womens Hospital (MWH) of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

Background:

Limited data from the U.S. and overseas has been reported on the natural history of high risk(hr) HPV DNA positive women screened with negative conventional Pap smear results, but no reports have documented follow-up of cytology negative- HPV positive women routinely screened with newer methods of liquid-based cytology (LBC), computer-assisted screening, and HPV reflex or co-testing. The purpose of this study was to document the development of cytological and histological abnormalities among several hundred women who tested hrHPV DNA positive along with negative computer-imaged liquid-based Pap co-test results (DNAwithPap).

Design:

The computerized hospital records of MWH were searched for patients reported as negative on ThinPrep Imaging System (TIS)-imaged ThinPrep Pap tests (TPPT) who also had positive Hybrid Capture 2 (HC2) hrHPV DNAwithPap co-test results over a 30 month span between July 2005 and December 2007. Cytologic and histologic follow-up outcomes were analyzed.

Results:

During the study period 402 women with negative TPPT and concurrent positive HC2 hrHPV DNA test results had documented cytologic and/or histologic follow-up. Histologic follow-up included 111 women who underwent cervical biopsy with or without ECC and 39 who underwent ECC alone. The mean age was 41.6 years (15-84 years). The average follow-up period was 13 months, ranging from 1 to 35 months (mean 10.6 m). Follow-up results documented that 8 of 402 (2.0%) women had tissue diagnoses of intraepithelial neoplasia 2+, including, four CIN2, 2 CIN3, one VAIN3, and one case of AIS on biopsy and microinvasive endocervical adenocarcinoma on subsequent conization. CIN1 or LSIL were confirmed in 61 (15.2%) and 82 (20.4%) had follow-up ASC-US Pap test results without biopsy findings of CIN1+. All CIN 2+ and 50 of 61 CIN 1 lesions were diagnosed based on histology. The interval between positive HPV and negative TPPT findings and an initial diagnosis of CIN 2+ ranged from 1 month to 19 months (median 14 months).

Conclusion:

CIN3, often proposed as a surrogate for invasive cervical cancer in cervical screening trials, was detected on initial follow-up (average 13 months) in 2 of 402 women (0.5%) with negative computer-imaged TPPT and positive HPV co-test results. Inclusion of two additional cases of histologically detected CIN2, one VAIN3, and one case of AIS with microinvasive endocervical adenocarcinoma potentially alters the risk profile of this cohort of over 400 cytology negative HPV positive patients. Additional natural history studies are needed on cytology negative HPV positive women routinely screened with modern methods which are now prevalent in the U.S. The potential benefits of routinely combining LBC and HPV co-testing for enhanced detection of endocervical neoplasia deserves special study, given the limited reported success of screening in this area to date.

Table 1

Cytologic and histologic follow-up results among 402 women with positive HPV tests and negative Pap tests

Follow-up	No.	%
Negative	251	62.4
ASC-US	82	20.4
CIN 1/LSIL	61	15.2
CIN 2	4	1.0
CIN3	2	0.5
VAIN3/AIS	2	0.5

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4 楼发表于2009-06-12 23:24:00举报|引用
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Abstract

The previous history of cytological and histological abnormalities among women with negative computer-imaged liquid-based Pap and positive HPV DNA test results

Anisa Kanbour, MD, Shuping Zhao, MD/PhD, Amal Kanbour-Shakir, MD/PhD, Chengquan Zhao Zhao, MD.
Magee Womens Hospital, UPMC, Pittsburgh, PA, USA.

Abstract:
Introduction:
No reports have documented the previous Pap test history for women with cytology negative- HPV positive testing results with methods of liquid-based cytology (LBC), computer-assisted screening, and HPV co-testing. The purpose of this study was to document the abnormal cytology and/or positive HPV testing results among women who tested hrHPV DNA positive along with negative computer-imaged liquid-based Pap co-test results.

Materials and methods:
The computerized hospital records of MWH were searched for patients reported as negative on ThinPrep Imaging System (TIS)-imaged ThinPrep Pap tests (TPPT) who also had positive Hybrid Capture 2 (HC2) hrHPV DNAwithPap co-test results between January 2008 and June 2008. The previous Pap cytology and HPV testing results for these women were analyzed. For women has two or more abnormal Pap tests or biopsy results, only the most abnormal diagnosis was recorded.

Results:
During the study period 202 women had negative TPPT and concurrent positive HC2 hrHPV DNA test results. 71 women showed no previous Pap tests and HPV testing in our files. 131 women had documented previous cytologic and/or HPV testing, or cervical biopsy results. Among these women, 55 (42%) showed normal Pap test and/or negative HPV testing history, 76 (58.0%) had at least one time of abnormal Pap tests or biopsy or Positive HPV testing results previously (Table 1).The interval between an initial abnormal Pap test and current positive HPV and negative TPPT findings ranged from 6 month to 13 years with average of 2.9 years. 71 of 76 cases (93.4%) had the first atypical Pap tests within 5 years.

Conclusion:
Our study indicates that more than half of the women (58%) with negative computer-imaged TPPT and positive HPV co-test results had previous abnormal Pap test or positive HPV testing history. HPV positivity predicts subsequent infection even though the risk of developing high grade dysplasia in women with negative Pap and positive HPV testing is very low. The previous Pap test, cervical biopsy, and HPV testing result should be considered for the risk assessment for cytology negative HPV positive women.

Cytologic and histologic abnormalities among 202 women with positive HPV tests and negative Pap test

Previous history

No.

%

No history

71

35.1

Negative

55

27.2

ASC-US

44

21.8

CIN 1/LSIL

24*

11.9

CIN 2

2

1.0

Pap-HPV+

6

3.0

Total HPV+

47

23.3

Abstract

The previous history of cytological and histological abnormalities among women with negative computer-imaged liquid-based Pap and positive HPV DNA test results

Anisa Kanbour, MD, Shuping Zhao, MD/PhD, Amal Kanbour-Shakir, MD/PhD, Chengquan Zhao Zhao, MD.
Magee Womens Hospital, UPMC, Pittsburgh, PA, USA.

Abstract:
Introduction:
No reports have documented the previous Pap test history for women with cytology negative- HPV positive testing results with methods of liquid-based cytology (LBC), computer-assisted screening, and HPV co-testing. The purpose of this study was to document the abnormal cytology and/or positive HPV testing results among women who tested hrHPV DNA positive along with negative computer-imaged liquid-based Pap co-test results.

Materials and methods:
The computerized hospital records of MWH were searched for patients reported as negative on ThinPrep Imaging System (TIS)-imaged ThinPrep Pap tests (TPPT) who also had positive Hybrid Capture 2 (HC2) hrHPV DNAwithPap co-test results between January 2008 and June 2008. The previous Pap cytology and HPV testing results for these women were analyzed. For women has two or more abnormal Pap tests or biopsy results, only the most abnormal diagnosis was recorded.

Results:
During the study period 202 women had negative TPPT and concurrent positive HC2 hrHPV DNA test results. 71 women showed no previous Pap tests and HPV testing in our files. 131 women had documented previous cytologic and/or HPV testing, or cervical biopsy results. Among these women, 55 (42%) showed normal Pap test and/or negative HPV testing history, 76 (58.0%) had at least one time of abnormal Pap tests or biopsy or Positive HPV testing results previously (Table 1).The interval between an initial abnormal Pap test and current positive HPV and negative TPPT findings ranged from 6 month to 13 years with average of 2.9 years. 71 of 76 cases (93.4%) had the first atypical Pap tests within 5 years.

Conclusion:
Our study indicates that more than half of the women (58%) with negative computer-imaged TPPT and positive HPV co-test results had previous abnormal Pap test or positive HPV testing history. HPV positivity predicts subsequent infection even though the risk of developing high grade dysplasia in women with negative Pap and positive HPV testing is very low. The previous Pap test, cervical biopsy, and HPV testing result should be considered for the risk assessment for cytology negative HPV positive women.

Cytologic and histologic abnormalities among 202 women with positive HPV tests and negative Pap test

Previous history

No.

%

No history

71

35.1

Negative

55

27.2

ASC-US

44

21.8

CIN 1/LSIL

24*

11.9

CIN 2

2

1.0

Pap-HPV+

6

3.0

Total HPV+

47

23.3

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5 楼发表于2009-06-12 23:22:00举报|引用
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Abstract (will work on paper soon)

Histological Follow-up Findings in Adolescents with HSIL Cytology Results

Chengquan Zhao, MD, Pal Kalposi-Novak, MD, R. Mashall Austin, MD, Dr.
Magee Womens Hospital, UPMC, Pittsburgh, PA, USA.

Abstract:
Introduction:
The incidence of cervical intraepithelial lesions is increased in adolescents and reflects the high prevalence of hrHPV infection in this special population. Recent follow-up guidelines emphasize conservative follow-up options. Furthermore, data from cohort studies suggest that regression of both low grade and high grade CIN are quite frequent in very young women. In this study we analyzed histological follow-up data for adolescent women who had HSIL cytology reports. We also assessed the effect of presence or absence of an adequate TZ/ECS in liquid-based Pap tests on the follow-up biopsy diagnoses.
Materials and methods:
The computerized records of a large academic women’s hospital were searched for cases reported as HSIL on TPPT in women age 20 or younger over a 6 year span between January 2002 and December, 2007. Histologic and Pap follow-up results, variations among age groups of adolescent women, and impact of presence or absence of TZ/ECS in Pap test were analyzed. Chi-Square test analysis was performed using SAS 9.1 System.
Results:
During the study period a total of 474 women age 20 or younger had HSIL Pap test results. 335 adolescent women with at least one cervical biopsy with or without endocervical curettage were included in the analysis. The average age was 18.6 years (13-20 years). The average follow-up period was 24 months (0 to 75 months) with a median of 22 months. The overall histologic CIN2/3 and detection rate was 44.2% and 47.8% for CIN1. The average period between the HSIL Pap test and an initial diagnosis of CIN2/3 was 5 months (0-62 months) with a median 2 months. The rates for histologic documentation of CIN in women age 19-20 compared to younger women were not statistically different. Detailed histologic findings are shown in Table 1. No invasive carcinomas or adenocarcinoma in situ cases were identified in this series of adolescents. The percentage of CIN 2/3 diagnosed on histologic follow up was not statistically significantly different when comparing women with and without a TZ/ECS in their preceding HSIL Pap tests (44.5% vs. 38.9%, p=0.642).
Conclusion:
Less than half of adolescent patients with HSIL cytology results had documented histologic CIN2/3 over an average follow-up period of 24 months, and no cases of invasive carcinoma were identified. CIN1 histologic follow-up findings were as common as CIN2/3 findings, likely reflecting both the increased likelihood of HSIL regression in younger women as well as the challenges of precise cytologic and histologic classification. High rates of hrHPV infection, only moderate rates of histologic CIN2/3 following HSIL cytology, and absence of invasive carcinoma all mark the adolescent group as a unique subset of patients deserving further study. Identification of additional biomarkers for HSIL progression would be useful.

Histologic Follow-up Finding in Adolescent Women with HSIL Cytology

Age (y)

F/U No

Negative (%)

CIN 1 (%)

CIN 2/3 (%)

19-20

199

13 (6.5)

94 (47.2)

92 (46.2)

<19

136

14 (10.3)

66 (48.5)

56 (41.2)

Total

335

27 (8.1)

160 (47.8)

148 (44.2)

Abstract (will work on paper soon)

Histological Follow-up Findings in Adolescents with HSIL Cytology Results

Chengquan Zhao, MD, Pal Kalposi-Novak, MD, R. Mashall Austin, MD, Dr.
Magee Womens Hospital, UPMC, Pittsburgh, PA, USA.

Abstract:
Introduction:
The incidence of cervical intraepithelial lesions is increased in adolescents and reflects the high prevalence of hrHPV infection in this special population. Recent follow-up guidelines emphasize conservative follow-up options. Furthermore, data from cohort studies suggest that regression of both low grade and high grade CIN are quite frequent in very young women. In this study we analyzed histological follow-up data for adolescent women who had HSIL cytology reports. We also assessed the effect of presence or absence of an adequate TZ/ECS in liquid-based Pap tests on the follow-up biopsy diagnoses.
Materials and methods:
The computerized records of a large academic women’s hospital were searched for cases reported as HSIL on TPPT in women age 20 or younger over a 6 year span between January 2002 and December, 2007. Histologic and Pap follow-up results, variations among age groups of adolescent women, and impact of presence or absence of TZ/ECS in Pap test were analyzed. Chi-Square test analysis was performed using SAS 9.1 System.
Results:
During the study period a total of 474 women age 20 or younger had HSIL Pap test results. 335 adolescent women with at least one cervical biopsy with or without endocervical curettage were included in the analysis. The average age was 18.6 years (13-20 years). The average follow-up period was 24 months (0 to 75 months) with a median of 22 months. The overall histologic CIN2/3 and detection rate was 44.2% and 47.8% for CIN1. The average period between the HSIL Pap test and an initial diagnosis of CIN2/3 was 5 months (0-62 months) with a median 2 months. The rates for histologic documentation of CIN in women age 19-20 compared to younger women were not statistically different. Detailed histologic findings are shown in Table 1. No invasive carcinomas or adenocarcinoma in situ cases were identified in this series of adolescents. The percentage of CIN 2/3 diagnosed on histologic follow up was not statistically significantly different when comparing women with and without a TZ/ECS in their preceding HSIL Pap tests (44.5% vs. 38.9%, p=0.642).
Conclusion:
Less than half of adolescent patients with HSIL cytology results had documented histologic CIN2/3 over an average follow-up period of 24 months, and no cases of invasive carcinoma were identified. CIN1 histologic follow-up findings were as common as CIN2/3 findings, likely reflecting both the increased likelihood of HSIL regression in younger women as well as the challenges of precise cytologic and histologic classification. High rates of hrHPV infection, only moderate rates of histologic CIN2/3 following HSIL cytology, and absence of invasive carcinoma all mark the adolescent group as a unique subset of patients deserving further study. Identification of additional biomarkers for HSIL progression would be useful.

Histologic Follow-up Finding in Adolescent Women with HSIL Cytology

Age (y)

F/U No

Negative (%)

CIN 1 (%)

CIN 2/3 (%)

19-20

199

13 (6.5)

94 (47.2)

92 (46.2)

<19

136

14 (10.3)

66 (48.5)

56 (41.2)

Total

335

27 (8.1)

160 (47.8)

148 (44.2)

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6 楼发表于2009-06-12 23:19:00举报|引用
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CAP Nov. 2009 abstract (will work on paper soon)

Significance of hrHPV Testing in Women Age 50 Years or Older with LSIL and HSIL Cytology

Chengquan Zhao, MD (zhaoc@upmc.edu); Amer Heider, MD; R Mashall Austin, MD/PhD. Department of Pathology, Magee Womens Hospital, UPMC, Pittsburgh, Pa.

Abstract:
Context:
Older women are considered a “special population”. 2006 ASCCP Guidelines support reflex hrHPV testing as an option for postmenopausal women with LSIL. The data of hrHPV infection and its association to histologic CIN 2/3 in older women with LSIL and HSIL cytology are limited.
Design:
A computer-based search of Copath files of Magee-Womens Hospital, UPMC was carried out between July 1, 2005 and June 30, 2008 to retrieve women aged 50 years or above reported as LSIL or HSIL cytology who also were tested for hrHPV DNA (HC2). The HPV testing result, Pap and histologic follow up results were recorded.
Results:
hrHPV DNA was detected in 25 of 28 (89.3%) women age 50 or older with HSIL cytology, and in 154 of 217 (71.0%) women age 50 or older with LSIL cytology. The average interval between SIL cytology and an initial diagnosis of CIN 2/3 was 2.6 months (0 to 22 months) in women with HSIL cytology, and was 10.4 months (0-35 months) in women with LSIL cytology.The histologic findings are listed in the Table 1.
Histologic CIN Lesions between hrHPV Positive and Negative Testing Results in Older Women with LSIL and HSIL Cytology


	hrHPV Positive				hrHPV Negative
	F/U No	CIN 1 (%)	CIN 2 (%)	CIN 3 (%)	F/U No	CIN 1 (%)	CIN 2 (%)	CIN 3 (%)
HSIL	21	2 (9.5)	9 (42.9)	10 (47.6)	3	0	1 (33.3)	1 (33.3)
LSIL	82	48 (58.5)	6 (7.3)	2 (2.4)	24	11 (45.8)	0	0

	hrHPV Positive	hrHPV Negative
	F/U No	CIN 1 (%)	CIN 2 (%)	CIN 3 (%)	F/U No	CIN 1 (%)	CIN 2 (%)	CIN 3 (%)
HSIL	21	2 (9.5)	9 (42.9)	10 (47.6)	3	0	1 (33.3)	1 (33.3)
LSIL	82	48 (58.5)	6 (7.3)	2 (2.4)	24	11 (45.8)	0	0

Conclusions:
The incidence of histologic CIN 2/3 was markedly higher in women with HSIL cytology than women with LSIL cytology. No CIN 2/3 was noted in older women with LSIL cytology and negative hrHPV testing. hrHPV testing might be helpful for risk assessment for older women with LSIL cytology, but not for older women with HSIL cytology.
:

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7 楼发表于2009-06-12 23:14:00举报|引用
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Gynecol Oncol. 2007 Nov;107(2):231-5. Epub 2007 Sep 14.

Human papillomavirus DNA detection in ThinPrep Pap test vials is independent of cytologic sampling of the transformation zone.

Zhao C, Austin RM.

Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, 300 Halket Street, Pittsburgh, PA 15213-3180, USA.

OBJECTIVE: Sampling of the transformation zone (TZ) and endocervical cells (EC) has been widely regarded as a quality indicator in cervical screening programs; however, the significance of a TZ/EC sample (TZ/ECS) in promoting disease detection remains a matter of controversy. Because little data are available on the relationship between TZ/EC sampling and HPV DNA test results, we examined whether or not there is a measurable association between high-risk human papillomavirus (hrHPV) DNA test results and TZ/EC sampling in several thousand women screened in a large academic women's hospital laboratory. METHODS: 9035 ThinPrep Pap tests (TPPT) reported as negative, LSIL, or HSIL and which also had Hybrid capture 2 (HC2) hrHPV DNA testing over an 18 month period between July 1, 2005 and December 31, 2006 were documented. 8415 negative, 526 LSIL, and 84 HSIL TPPT were included in the study. The age of patients, the presence or absence of a TZ/ECS, and hrHPV DNA test results were noted from CoPath data files. Patients were stratified into 10 year age groups for data analysis. RESULTS: An identical 2.8% of Pap negative patients were hrHPV DNA positive in both the 6709 cytology negative patients with a TZ/ECS and the 1706 cytology negative patients without a TZ/ECS. Neither were statistically significant differences noted for hrHPV DNA prevalence in patients with SIL Pap test results from women with and without a TZ/ECS. CONCLUSIONS: HC2 hrHPV DNA detection in TPPT vials is independent of cytologic sampling of the transformation zone. hrHPV DNA results provide for the first time an available objective basis for risk assessment of patients with no TZ/ECS. The observation that hrHPV DNA test status is independent of presence or absence of a TZ/ECS is consistent with longitudinal studies of Pap negative women with no TZ/ECS which have not found increased disease on follow-up.

Gynecol Oncol. 2007 Nov;107(2):231-5. Epub 2007 Sep 14.

Human papillomavirus DNA detection in ThinPrep Pap test vials is independent of cytologic sampling of the transformation zone.

Zhao C, Austin RM.

Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, 300 Halket Street, Pittsburgh, PA 15213-3180, USA.

OBJECTIVE: Sampling of the transformation zone (TZ) and endocervical cells (EC) has been widely regarded as a quality indicator in cervical screening programs; however, the significance of a TZ/EC sample (TZ/ECS) in promoting disease detection remains a matter of controversy. Because little data are available on the relationship between TZ/EC sampling and HPV DNA test results, we examined whether or not there is a measurable association between high-risk human papillomavirus (hrHPV) DNA test results and TZ/EC sampling in several thousand women screened in a large academic women's hospital laboratory. METHODS: 9035 ThinPrep Pap tests (TPPT) reported as negative, LSIL, or HSIL and which also had Hybrid capture 2 (HC2) hrHPV DNA testing over an 18 month period between July 1, 2005 and December 31, 2006 were documented. 8415 negative, 526 LSIL, and 84 HSIL TPPT were included in the study. The age of patients, the presence or absence of a TZ/ECS, and hrHPV DNA test results were noted from CoPath data files. Patients were stratified into 10 year age groups for data analysis. RESULTS: An identical 2.8% of Pap negative patients were hrHPV DNA positive in both the 6709 cytology negative patients with a TZ/ECS and the 1706 cytology negative patients without a TZ/ECS. Neither were statistically significant differences noted for hrHPV DNA prevalence in patients with SIL Pap test results from women with and without a TZ/ECS. CONCLUSIONS: HC2 hrHPV DNA detection in TPPT vials is independent of cytologic sampling of the transformation zone. hrHPV DNA results provide for the first time an available objective basis for risk assessment of patients with no TZ/ECS. The observation that hrHPV DNA test status is independent of presence or absence of a TZ/ECS is consistent with longitudinal studies of Pap negative women with no TZ/ECS which have not found increased disease on follow-up.

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8 楼发表于2009-06-12 23:12:00举报|引用
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Cancer. 2007 Oct 25;111(5):292-7.

Very low Human Papillomavirus DNA prevalence in mature women with negative computer-imaged liquid-based Pap tests.

Zhao C, Elishaev E, Yuan KH, Yu J, Marshall Austin R.

Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. zhaoc@UPMC.edu

BACKGROUND: The prevalence of high-risk Human Papillomavirus DNA (hrHPV DNA) in women with negative Papanicolaou (Pap) test results provides a measure of residual risk for cervical neoplasia after cytology screening. The purpose of this study was to document the prevalence of hrHPV DNA in several thousand women ages > or =30 years with negative ThinPrep Imaging System (TIS)-imaged Pap test results in a large academic hospital cytology laboratory. METHODS: All cytology-negative TIS-imaged ThinPrep Pap tests (TPPT) with hrHPV DNA tests that were performed by the United States Food and Drug Administration (FDA)-approved Hybrid Capture 2 (HC2) method from May 1, 2005 to November 20, 2006 were identified and reviewed. Imaged-negative Pap test slides associated with a positive hrHPV DNA test result were rescreened manually. Variation in hrHPV DNA prevalence was assessed for different age and ethnic groups. RESULTS: Of 8070 imaged cytology-negative TPPT from women ages 11 to 90 years, hrHPV DNA test results were also available. Among 7426 women ages > or =30 years with a cytology-negative, TIS-imaged, Pap test, a significant age-associated decline in hrHPV DNA prevalence was noted, 3.4% in 3050 women ages 30-45 years, 2.4% in 7426 women ages 30-90 years, and 1.8% in 5491 women ages 40-90 years. The hrHPV DNA-positive rate was 2.3% in 6012 imaged cytology-negative white women and 4.1% in 739 imaged cytology-negative black women. CONCLUSIONS: Very low HC2 hrHPV DNA rates in 7426 women ages > or =30 years with cytology-negative, TIS-imaged, ThinPrep, Pap tests were similar to recently published data from 1 other academic center and lower than rates reported in previous studies on cytology-negative North American or European women screened manually with conventional or liquid-based Pap tests. These data may impact assessments of how best to combine cytology and HPV testing.

Cancer. 2007 Oct 25;111(5):292-7.

Very low Human Papillomavirus DNA prevalence in mature women with negative computer-imaged liquid-based Pap tests.

Zhao C, Elishaev E, Yuan KH, Yu J, Marshall Austin R.

Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. zhaoc@UPMC.edu

BACKGROUND: The prevalence of high-risk Human Papillomavirus DNA (hrHPV DNA) in women with negative Papanicolaou (Pap) test results provides a measure of residual risk for cervical neoplasia after cytology screening. The purpose of this study was to document the prevalence of hrHPV DNA in several thousand women ages > or =30 years with negative ThinPrep Imaging System (TIS)-imaged Pap test results in a large academic hospital cytology laboratory. METHODS: All cytology-negative TIS-imaged ThinPrep Pap tests (TPPT) with hrHPV DNA tests that were performed by the United States Food and Drug Administration (FDA)-approved Hybrid Capture 2 (HC2) method from May 1, 2005 to November 20, 2006 were identified and reviewed. Imaged-negative Pap test slides associated with a positive hrHPV DNA test result were rescreened manually. Variation in hrHPV DNA prevalence was assessed for different age and ethnic groups. RESULTS: Of 8070 imaged cytology-negative TPPT from women ages 11 to 90 years, hrHPV DNA test results were also available. Among 7426 women ages > or =30 years with a cytology-negative, TIS-imaged, Pap test, a significant age-associated decline in hrHPV DNA prevalence was noted, 3.4% in 3050 women ages 30-45 years, 2.4% in 7426 women ages 30-90 years, and 1.8% in 5491 women ages 40-90 years. The hrHPV DNA-positive rate was 2.3% in 6012 imaged cytology-negative white women and 4.1% in 739 imaged cytology-negative black women. CONCLUSIONS: Very low HC2 hrHPV DNA rates in 7426 women ages > or =30 years with cytology-negative, TIS-imaged, ThinPrep, Pap tests were similar to recently published data from 1 other academic center and lower than rates reported in previous studies on cytology-negative North American or European women screened manually with conventional or liquid-based Pap tests. These data may impact assessments of how best to combine cytology and HPV testing.

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9 楼发表于2009-06-12 23:11:00举报|引用
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TABLE 1

Age-Associated Absence of an EC/TZS in 10 Year Age Intervals (All TBS 2001 Pap Result Categories Included)

Age group

Total No.

TZ/ECS absent

%

95% CI

P value

10-19

7193

1239

20.81

19.87-21.75

0.0011

20-29

35906

5858

16.32

15.94-16.70

0.0209

30-39

29628

4614

15.57

15.16-15.98

Reference

40-49

31416

4870

15.50

15.10-15.90

0.8076

50-59

26765

6554

24.49

23.97-25.01

<1x10^-4

60-69

12530

4224

33.71

32.88-34.54

<1x10^-4

All

143438

27359

19.07

18.87-19.27

EC/ TZS indicates endocervical/ transformation zone sample.

P value was calculated by comparing each group with reference group.

TABLE 2

Comparison of LSIL Prevalence in Women with and without an EC/TZS (10 Year Age Intervals)

Age group

EC/TZS present

EC/TZS absent

P value

Total No

LSIL No

%

95% CI

Total No

LSIL No

%

95% CI

10-19

5954

849

14.26

13.37-15.15

1239

129

10.41

8.71-12.11

3x10^-4

20-29

30048

2665

8.87

8.55-9.19

5858

490

8.36

7.65-9.07

0.212

30-39

25014

811

3.24

3.02-3.46

4614

108

2.34

1.90-2.78

0.001

40-49

26546

577

2.17

1.99-2.35

4870

95

1.95

1.56-2.34

0.323

50-59

20211

256

1.27

1.12-1.42

6554

77

1.18

0.92-1.44

0.560

60-69

8306

75

0.90

0.70-1.10

4224

23

0.55

0.37-0.83

0.031

All

116079

5233

4.51

4.39-4.63

27359

922

3.37

3.16-3.58

<1x10^-4

LSIL indicates low grade squamous intraepithelial lesion; EC/TZS, endocervical/ transformation zone sample; TPPT, ThinPrep Pap test.

TABLE 3

Comparison of HSIL Prevalence in Women with and without an TZ/ECS (10 Year Age Intervals)

Age group

EC/TZS present

EC/TZS absent

P value

Total No

HSIL No

%

95% CI

Total No

HSIL No

%

95% CI

10-19

5954

82

1.38

1.08-1.68

1239

8

0.65

0.20-1.10

0.035

20-29

30048

429

1.43

1.30-1.56

5858

32

0.55

0.36-0.74

<1x10^-4

30-39

25014

199

0.80

0.69-0.91

4614

19

0.41

0.18-0.61

0.005

40-49

26546

79

0.30

0.23-0.37

4870

7

0.14

0.04-0.25

0.059

50-59

20211

36

0.18

0.12-0.24

6554

8

0.12

0.04-0.20

0.330

60-69

8306

12

0.15

0.06-0.22

4224

5

0.12

0.02-0.22

0.708

All

116079

837

0.72

0.67-0.77

27359

79

0.29

0.23-0.35

<1x10^-4

HSIL indicates high grade squamous intraepithelial lesion; EC/TZS, endocervical/ transformation zone sample; TPPT, ThinPrep Pap test.

TABLE 4

hrHPV DNA Detection Rates in 526 Women with LSIL with and without an EC/TZ (10 Year Age Intervals)

Age

group

EC/TZS present

EC/TZS absent

P value*

Total No

EC/TZS

present

%

HPV tested

Positive

%

95% CI

HPV tested

Positive

%

95% CI

10-19

36

32

88.9

78.6-99.2

5

4

80.0

44.9-100.0

0.4969

41

36

87.8

20-29

169

149

88.2

83.3-93.1

37

27

73.0

58.7-87.3

0.0357

206

169

82.0

30-39

101

80

79.2

71.3-87.1

15

10

66.7

42.8-90.6

0.3213

116

101

87.1

40-49

79

52

65.8

55.3-76.3

13

10

76.9

54.0-99.8

0.5352

92

79

85.9

50-59

38

26

68.4

53.6-83.2

13

8

61.5

35.0-88.0

0.7379

51

38

74.5

60-69

14

11

78.6

57.1-100.0

6

5

83.3

53.5-100.0

1.0000

20

14

70.0

All

437

350

80.1

76.4-83.8

89

64

71.9

62.6-81.2

0.0898

526

437

83.1

LSIL indicates low grade squamous intraepithelial lesion; EC/TZS, endocervical/ transformation zone sample; TPPT, ThinPrep Pap test, hrHPV, high risk human papillomavirus.

*P value was calculated by Fishers’ exact test.

TABLE 5

hrHPV DNA Detection Rates in 133 Women with HSIL with and without TZ/ECS (10 year age intervals)

Age

group

EC/TZS present

EC/TZS absent

P value*

Total No

EC/TZS

present

%

HPV tested

Positive

%

95% CI

HPV tested

Positive

%

95% CI

10-

9

100

100-100

0

-

9

100.0

20-

42

41

97.6

93.0-100

4

100

100-100

1.0000

46

42

91.3

30-

46

41

89.1

80.1-98.1

2

100

100-100

1.0000

48

46

95.8

40-

14

13

92.9

79.5-100

0

-

14

100.0

50-

8

6

75.0

45.0-100

1

100

100-100

1.0000

9

8

88.9

60-

4

3

75.0

32.6-100

3

2

66.7

13.4-100

1.0000

7

4

57.1

All

123

113

91.9

87.1-96.7

10

9

90.0

71.4-100

0.5916

133

123

92.5

TABLE 1

Age-Associated Absence of an EC/TZS in 10 Year Age Intervals (All TBS 2001 Pap Result Categories Included)

Age group

Total No.

TZ/ECS absent

%

95% CI

P value

10-19

7193

1239

20.81

19.87-21.75

0.0011

20-29

35906

5858

16.32

15.94-16.70

0.0209

30-39

29628

4614

15.57

15.16-15.98

Reference

40-49

31416

4870

15.50

15.10-15.90

0.8076

50-59

26765

6554

24.49

23.97-25.01

<1x10^-4

60-69

12530

4224

33.71

32.88-34.54

<1x10^-4

All

143438

27359

19.07

18.87-19.27

EC/ TZS indicates endocervical/ transformation zone sample.

P value was calculated by comparing each group with reference group.

TABLE 2

Comparison of LSIL Prevalence in Women with and without an EC/TZS (10 Year Age Intervals)

Age group

EC/TZS present

EC/TZS absent

P value

Total No

LSIL No

%

95% CI

Total No

LSIL No

%

95% CI

10-19

5954

849

14.26

13.37-15.15

1239

129

10.41

8.71-12.11

3x10^-4

20-29

30048

2665

8.87

8.55-9.19

5858

490

8.36

7.65-9.07

0.212

30-39

25014

811

3.24

3.02-3.46

4614

108

2.34

1.90-2.78

0.001

40-49

26546

577

2.17

1.99-2.35

4870

95

1.95

1.56-2.34

0.323

50-59

20211

256

1.27

1.12-1.42

6554

77

1.18

0.92-1.44

0.560

60-69

8306

75

0.90

0.70-1.10

4224

23

0.55

0.37-0.83

0.031

All

116079

5233

4.51

4.39-4.63

27359

922

3.37

3.16-3.58

<1x10^-4

LSIL indicates low grade squamous intraepithelial lesion; EC/TZS, endocervical/ transformation zone sample; TPPT, ThinPrep Pap test.

TABLE 3

Comparison of HSIL Prevalence in Women with and without an TZ/ECS (10 Year Age Intervals)

Age group

EC/TZS present

EC/TZS absent

P value

Total No

HSIL No

%

95% CI

Total No

HSIL No

%

95% CI

10-19

5954

82

1.38

1.08-1.68

1239

8

0.65

0.20-1.10

0.035

20-29

30048

429

1.43

1.30-1.56

5858

32

0.55

0.36-0.74

<1x10^-4

30-39

25014

199

0.80

0.69-0.91

4614

19

0.41

0.18-0.61

0.005

40-49

26546

79

0.30

0.23-0.37

4870

7

0.14

0.04-0.25

0.059

50-59

20211

36

0.18

0.12-0.24

6554

8

0.12

0.04-0.20

0.330

60-69

8306

12

0.15

0.06-0.22

4224

5

0.12

0.02-0.22

0.708

All

116079

837

0.72

0.67-0.77

27359

79

0.29

0.23-0.35

<1x10^-4

HSIL indicates high grade squamous intraepithelial lesion; EC/TZS, endocervical/ transformation zone sample; TPPT, ThinPrep Pap test.

TABLE 4

hrHPV DNA Detection Rates in 526 Women with LSIL with and without an EC/TZ (10 Year Age Intervals)

Age

group

EC/TZS present

EC/TZS absent

P value*

Total No

EC/TZS

present

%

HPV tested

Positive

%

95% CI

HPV tested

Positive

%

95% CI

10-19

36

32

88.9

78.6-99.2

5

4

80.0

44.9-100.0

0.4969

41

36

87.8

20-29

169

149

88.2

83.3-93.1

37

27

73.0

58.7-87.3

0.0357

206

169

82.0

30-39

101

80

79.2

71.3-87.1

15

10

66.7

42.8-90.6

0.3213

116

101

87.1

40-49

79

52

65.8

55.3-76.3

13

10

76.9

54.0-99.8

0.5352

92

79

85.9

50-59

38

26

68.4

53.6-83.2

13

8

61.5

35.0-88.0

0.7379

51

38

74.5

60-69

14

11

78.6

57.1-100.0

6

5

83.3

53.5-100.0

1.0000

20

14

70.0

All

437

350

80.1

76.4-83.8

89

64

71.9

62.6-81.2

0.0898

526

437

83.1

LSIL indicates low grade squamous intraepithelial lesion; EC/TZS, endocervical/ transformation zone sample; TPPT, ThinPrep Pap test, hrHPV, high risk human papillomavirus.

*P value was calculated by Fishers’ exact test.

TABLE 5

hrHPV DNA Detection Rates in 133 Women with HSIL with and without TZ/ECS (10 year age intervals)

Age

group

EC/TZS present

EC/TZS absent

P value*

Total No

EC/TZS

present

%

HPV tested

Positive

%

95% CI

HPV tested

Positive

%

95% CI

10-

9

100

100-100

0

-

9

100.0

20-

42

41

97.6

93.0-100

4

100

100-100

1.0000

46

42

91.3

30-

46

41

89.1

80.1-98.1

2

100

100-100

1.0000

48

46

95.8

40-

14

13

92.9

79.5-100

0

-

14

100.0

50-

8

6

75.0

45.0-100

1

100

100-100

1.0000

9

8

88.9

60-

4

3

75.0

32.6-100

3

2

66.7

13.4-100

1.0000

7

4

57.1

All

123

113

91.9

87.1-96.7

10

9

90.0

71.4-100

0.5916

133

123

92.5

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10 楼发表于2009-06-12 23:02:00举报|引用
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Cancer. 2008 Aug 25;114(4):242-8.

Adjunctive high-risk human papillomavirus DNA testing is a useful option for disease risk assessment in patients with negative Papanicolaou tests without an endocervical/transformation zone sample.

Zhao C, Austin RM.

Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, 300 Halket Street, Pittsburgh, PA 15213, USA. zhaoc@UPMC.edu

BACKGROUND: Current guidelines recommend that women with negative Papanicolaou (Pap) test results and no endocervical/transformation zone (EC/TZ) sample return for screening within 12 months. For some women, this represents earlier follow-up than advocated in several routine screening guidelines. Controversy remains with regard to the correlation between sampling of the EC/TZ, Pap test quality, and disease risk assessment. METHODS: A retrospective study was conducted reviewing the results from 143,438 liquid-based cervical Pap tests performed at a large academic women's hospital between July 2005 and December 2006. Vaginal Pap tests were excluded from the study. Women with any Pap result, women with low-grade squamous intraepithelial lesions (LSILs), and patients with high-grade squamous intraepithelial lesion (HSIL) Pap test results were stratified by 10-year age groups and according to the presence or absence of an EC/TZ sample (EC/TZS). Women with LSIL and HSIL Pap test results with and without an EC/TZS were also compared for rates of high-risk human papillomavirus (hrHPV) DNA detection. RESULTS: Of the total of 143,438 cervical Pap tests performed, 27,359 (19.1%) were reported to be lacking an EC/TZS. The absence of an EC/TZS was found to be highest in adolescents and in mature women aged >or=50 years. The overall detection rate of LSIL was 4.29% and that of HSIL was 0.64%. Both the LSIL and HSIL rates were found to be significantly higher in Pap tests with an EC/TZS compared with Pap tests without an EC/TZS (LSIL: 4.51% vs 3.37% and HSIL: 0.72% vs 0.29%). However, when women with LSILs and HSILs were divided into a group in which EC/TZS was present and a group in which EC/TZS was absent, no significant differences were found to be present with regard to hrHPV DNA rates between the 2 groups. CONCLUSIONS: Adjunctive hrHPV DNA testing is effective in stratifying risk for the presence of SIL in women with and without an EC/TZS. This finding is consistent with recently reported data from >9000 patients with negative Pap results, which found that hrHPV DNA-positive test rates are independent of the presence or absence of an EC/TZS. hrHPV DNA results provide a useful new optional adjunctive tool for the objective stratification of disease risk in women with negative Pap tests and no EC/TZS. (c) 2008 American Cancer Society.

Cancer. 2008 Aug 25;114(4):242-8.

Adjunctive high-risk human papillomavirus DNA testing is a useful option for disease risk assessment in patients with negative Papanicolaou tests without an endocervical/transformation zone sample.

Zhao C, Austin RM.

Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, 300 Halket Street, Pittsburgh, PA 15213, USA. zhaoc@UPMC.edu

BACKGROUND: Current guidelines recommend that women with negative Papanicolaou (Pap) test results and no endocervical/transformation zone (EC/TZ) sample return for screening within 12 months. For some women, this represents earlier follow-up than advocated in several routine screening guidelines. Controversy remains with regard to the correlation between sampling of the EC/TZ, Pap test quality, and disease risk assessment. METHODS: A retrospective study was conducted reviewing the results from 143,438 liquid-based cervical Pap tests performed at a large academic women's hospital between July 2005 and December 2006. Vaginal Pap tests were excluded from the study. Women with any Pap result, women with low-grade squamous intraepithelial lesions (LSILs), and patients with high-grade squamous intraepithelial lesion (HSIL) Pap test results were stratified by 10-year age groups and according to the presence or absence of an EC/TZ sample (EC/TZS). Women with LSIL and HSIL Pap test results with and without an EC/TZS were also compared for rates of high-risk human papillomavirus (hrHPV) DNA detection. RESULTS: Of the total of 143,438 cervical Pap tests performed, 27,359 (19.1%) were reported to be lacking an EC/TZS. The absence of an EC/TZS was found to be highest in adolescents and in mature women aged >or=50 years. The overall detection rate of LSIL was 4.29% and that of HSIL was 0.64%. Both the LSIL and HSIL rates were found to be significantly higher in Pap tests with an EC/TZS compared with Pap tests without an EC/TZS (LSIL: 4.51% vs 3.37% and HSIL: 0.72% vs 0.29%). However, when women with LSILs and HSILs were divided into a group in which EC/TZS was present and a group in which EC/TZS was absent, no significant differences were found to be present with regard to hrHPV DNA rates between the 2 groups. CONCLUSIONS: Adjunctive hrHPV DNA testing is effective in stratifying risk for the presence of SIL in women with and without an EC/TZS. This finding is consistent with recently reported data from >9000 patients with negative Pap results, which found that hrHPV DNA-positive test rates are independent of the presence or absence of an EC/TZS. hrHPV DNA results provide a useful new optional adjunctive tool for the objective stratification of disease risk in women with negative Pap tests and no EC/TZS. (c) 2008 American Cancer Society.

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11 楼发表于2009-06-12 22:57:00举报|引用
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Submitted

The significance of high-risk human papillomavirus testing in women with LSIL Pap test

Amer Heider, RM Austin, C Zhao*

From the Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 15213

The authors have no relevant financial interest in the products or companies described in this article.

Presented orally at the 2009 USCAP Annual Meeting, Denver, Boston. March 2009

*Reprints: Chengquan Zhao MD, Department of Pathology, Magee-Womens Hospital of University of Pittsburgh Medical Center, 300 Halket Street, Pittsburgh, PA 15213 (e-mail: zhaoc@upmc.edu)

Background:

High risk (hr) HPV infection has been recognized as the primary risk factor for cervical carcinoma. Based primarily on ALTS data and American Society for Colposcopy and Cervical Pathology (ASCCP) Guidelines, LSIL cytology is most often managed with colposcopic evaluation. 2006 ASCCP Guidelines support reflex hrHPV testing as an acceptable option for postmenopausal women with LSIL. Data on the efficacy of hrHPV triage and histologic follow-up of women with LSIL and HPV test results in different age groups remain limited.

Design:

A computer-based search of Copath files of Magee-Womens Hospital of University of Pittsburgh Medical Center was carried out over a 34 month period between July 1, 2005 and April 30, 2008 to retrieve women reported to have LSIL who also were tested for hrHPV DNA. All liquid-based Pap tests were processed in the pathology laboratory at MWH and prepared using an automated processor and imaged using the ThinPrep Imaging System (TIS). Vaginal Pap tests were excluded from this study. hrHPV DNA detection was performed by the Hybrid Capture 2 (HC2) method. The HPV testing result, presence or absence of a TZ/ECS and histologic follow up results including endocervical curettage (ECC), cervical biopsy, loop electrosurgical excision procedure (LEEP) or cone biopsy were recorded. The patients who had only repeat Pap tests or ECC were not considered as having an effective follow-up.

Results: 719 women with LSIL cytology and hrHPV DNA testing who had at least one subsequent cervical biopsy during the study period were included. The histologic procedures included 98 LEEP/Cone biopsies and 10 hystectomies. The average follow-up period was 11 months, ranging from 0 to 35 months with a median 10.4 months. The interval between LSIL cytology and the initial diagnosis of CIN 2/3 ranged from 1 month to 29 months with a median 2.5 months (mean 6.9 months). Either CIN 2/3 or CIN 1 were identified on histologic follow up in a significant greater proportion of LSIL women with positive hrHPV results than in LSIL women with negative hrHPV testing (p=0.002 for CIN 2/3; p<0.001 for CIN 1). Detailed histologic findings are shown in Table 1. No CIN 2/3 was reported in women age 50 years or older with negative hrHPV test results. The percentage of CIN diagnosed on histologic follow up was not statistically significant between women with and without a TZ/ECS in their preceding LSIL cytology samples.

Conclusion:

The absence of histologic CIN2/3 in women 50 years and older with hrHPV negative LSIL in this series supports that triage using hrHPV testing may be an efficient alternative to colposcopy in postmenopausal women with LSIL cytology in 2006 ASCCP consensus guidelines for the management of women with abnormal cervical cancer screening tests. hrHPV DNA results also help to stratify risk for underlying CIN2/3 in younger women and deserves further investigation along with other biomarkers for cervical carcinogenesis.

Comparison of Age-Specific hrHPV Prevalence among Women with LSIL TPPT with and without TZ/ECS (10-Year Intervals)

Age

group

Tested

No

Positive

No

%

(95% CI)

TZ/ECS present

TZ/ECS absent

P

Tested

No

Positive

No

%

(95% CI)

Tested

No

Positive

No

%

(95% CI)

10-

99

91

92.0

86

79

91.9

13

12

92.3

1.0*

20

456

402

88.2

382

342

89.5

74

60

81.1

0.049

30-

326

261

80.1

281

228

81.1

45

33

73.3

0.498

40

271

189

69.7

232

160

69.0

39

29

74.4

0.498

50-

142

96

67.6

103

69

67.0

39

27

69.2

0.799

60-

49

39

79.6

36

29

80.5

13

10

76.9

1.0 *

≥70-

8

5

62.5

4

1

25.0

4

100.0

0.143*

Total

1351

1083

80.2

1124

908

80.8

227

175

77.1

0.185

Comparison of Histologic CIN between hrHPV Positive and Negative TPPT in LSIL Women Stratified by Ages

Age

Total

hrHPV Positive

hrHPV Negative

F/U No

CIN 2/3

(%)

CIN 1

(%)

F/U No

CIN 2/3

(%)

CIN 1

(%)

F/U No

CIN 2/3

(%)

CIN 1

(%)

10-19

44

6

(13.6)

29

(65.9)

40

6

(15.0)

26

(65.0)

4

0

(0.0)

3

(75.0)

20-29

234

24

(10.3)

141

(60.3)

211

23

(10.9)

128

(60.7)

23

1

(4.3)

13

(56.5)

30-39

189

31

(16.4)

94

(49.7)

164

30

(18.3)

84

(51.2)

25

1

(4.0)

10

(40.0)

40-49

156

24

(15.4)

82

52.6)

124

22*

(17.7)

75

(60.5)

32

2

(6.3)

7

(21.9)

50-59

67

3

(4.5)

40

(59.7)

48

3

(6.3)

31

(64.6)

19

0

(0.0)

9

(47.4)

≥60

29

5

(17.2)

15

(51.7)

25

5

(20.0)

13

(52.0)

4

0

(0.0)

2

(50.0)

Total

719

93

(12.9)

401

(55.8)

612

89

(14.6)

357

(58.3)

107

4

(3.7)

44

(41.1)

Submitted

The significance of high-risk human papillomavirus testing in women with LSIL Pap test

Amer Heider, RM Austin, C Zhao*

From the Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 15213

The authors have no relevant financial interest in the products or companies described in this article.

Presented orally at the 2009 USCAP Annual Meeting, Denver, Boston. March 2009

*Reprints: Chengquan Zhao MD, Department of Pathology, Magee-Womens Hospital of University of Pittsburgh Medical Center, 300 Halket Street, Pittsburgh, PA 15213 (e-mail: zhaoc@upmc.edu)

Background:

High risk (hr) HPV infection has been recognized as the primary risk factor for cervical carcinoma. Based primarily on ALTS data and American Society for Colposcopy and Cervical Pathology (ASCCP) Guidelines, LSIL cytology is most often managed with colposcopic evaluation. 2006 ASCCP Guidelines support reflex hrHPV testing as an acceptable option for postmenopausal women with LSIL. Data on the efficacy of hrHPV triage and histologic follow-up of women with LSIL and HPV test results in different age groups remain limited.

Design:

A computer-based search of Copath files of Magee-Womens Hospital of University of Pittsburgh Medical Center was carried out over a 34 month period between July 1, 2005 and April 30, 2008 to retrieve women reported to have LSIL who also were tested for hrHPV DNA. All liquid-based Pap tests were processed in the pathology laboratory at MWH and prepared using an automated processor and imaged using the ThinPrep Imaging System (TIS). Vaginal Pap tests were excluded from this study. hrHPV DNA detection was performed by the Hybrid Capture 2 (HC2) method. The HPV testing result, presence or absence of a TZ/ECS and histologic follow up results including endocervical curettage (ECC), cervical biopsy, loop electrosurgical excision procedure (LEEP) or cone biopsy were recorded. The patients who had only repeat Pap tests or ECC were not considered as having an effective follow-up.

Results: 719 women with LSIL cytology and hrHPV DNA testing who had at least one subsequent cervical biopsy during the study period were included. The histologic procedures included 98 LEEP/Cone biopsies and 10 hystectomies. The average follow-up period was 11 months, ranging from 0 to 35 months with a median 10.4 months. The interval between LSIL cytology and the initial diagnosis of CIN 2/3 ranged from 1 month to 29 months with a median 2.5 months (mean 6.9 months). Either CIN 2/3 or CIN 1 were identified on histologic follow up in a significant greater proportion of LSIL women with positive hrHPV results than in LSIL women with negative hrHPV testing (p=0.002 for CIN 2/3; p<0.001 for CIN 1). Detailed histologic findings are shown in Table 1. No CIN 2/3 was reported in women age 50 years or older with negative hrHPV test results. The percentage of CIN diagnosed on histologic follow up was not statistically significant between women with and without a TZ/ECS in their preceding LSIL cytology samples.

Conclusion:

The absence of histologic CIN2/3 in women 50 years and older with hrHPV negative LSIL in this series supports that triage using hrHPV testing may be an efficient alternative to colposcopy in postmenopausal women with LSIL cytology in 2006 ASCCP consensus guidelines for the management of women with abnormal cervical cancer screening tests. hrHPV DNA results also help to stratify risk for underlying CIN2/3 in younger women and deserves further investigation along with other biomarkers for cervical carcinogenesis.

Comparison of Age-Specific hrHPV Prevalence among Women with LSIL TPPT with and without TZ/ECS (10-Year Intervals)

Age

group

Tested

No

Positive

No

%

(95% CI)

TZ/ECS present

TZ/ECS absent

P

Tested

No

Positive

No

%

(95% CI)

Tested

No

Positive

No

%

(95% CI)

10-

99

91

92.0

86

79

91.9

13

12

92.3

1.0*

20

456

402

88.2

382

342

89.5

74

60

81.1

0.049

30-

326

261

80.1

281

228

81.1

45

33

73.3

0.498

40

271

189

69.7

232

160

69.0

39

29

74.4

0.498

50-

142

96

67.6

103

69

67.0

39

27

69.2

0.799

60-

49

39

79.6

36

29

80.5

13

10

76.9

1.0 *

≥70-

8

5

62.5

4

1

25.0

4

100.0

0.143*

Total

1351

1083

80.2

1124

908

80.8

227

175

77.1

0.185

Comparison of Histologic CIN between hrHPV Positive and Negative TPPT in LSIL Women Stratified by Ages

Age

Total

hrHPV Positive

hrHPV Negative

F/U No

CIN 2/3

(%)

CIN 1

(%)

F/U No

CIN 2/3

(%)

CIN 1

(%)

F/U No

CIN 2/3

(%)

CIN 1

(%)

10-19

44

6

(13.6)

29

(65.9)

40

6

(15.0)

26

(65.0)

4

0

(0.0)

3

(75.0)

20-29

234

24

(10.3)

141

(60.3)

211

23

(10.9)

128

(60.7)

23

1

(4.3)

13

(56.5)

30-39

189

31

(16.4)

94

(49.7)

164

30

(18.3)

84

(51.2)

25

1

(4.0)

10

(40.0)

40-49

156

24

(15.4)

82

52.6)

124

22*

(17.7)

75

(60.5)

32

2

(6.3)

7

(21.9)

50-59

67

3

(4.5)

40

(59.7)

48

3

(6.3)

31

(64.6)

19

0

(0.0)

9

(47.4)

≥60

29

5

(17.2)

15

(51.7)

25

5

(20.0)

13

(52.0)

4

0

(0.0)

2

(50.0)

Total

719

93

(12.9)

401

(55.8)

612

89

(14.6)

357

(58.3)

107

4

(3.7)

44

(41.1)

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12 楼发表于2009-06-12 22:47:00举报|引用
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本帖最后由于 2009-06-12 22:49:00 编辑

Arch Pathol Lab Med. 2009. In press.

Follow-Up Findings in Women with HPV-Positive ASC-US Screening Test Results in a Large Womens Hospital Practice

Henry Armah MD, PhD; R. Marshall Austin MD; PhD, David Dabbs MD; Chengquan Zhao* MD

From the Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 15213

The authors have no relevant financial interest in the products or companies described in this article.

Presented orally at the 2008 USCAP Annual Meeting, Denver, Colorado. March 1 – March 7, 2008

Reprints: Chengquan Zhao MD, Department of Pathology, Magee-Womens Hospital of University of Pittsburgh Medical Center, 300 Halket Street, Pittsburgh, PA 15213 (e-mail: zhaoc@upmc.edu)

ABSTRACT

Context.- Reflex HPV testing has been designated in consensus guidelines as “preferred” for women with ASC-US liquid-based cytology (LBC) results, and colposcopy is currently recommended for patients with HPV-positive ASCUS results. Data from large clinical practices utilizing newer screening methods and current cytology terminology remain limited.

Objectives.-We analyzed data from patients with ASCUS LBC and positive HPV test results. We also assessed the impact of the presence or absence of an endocervical cell/transformation zone sample (EC/TZS) on biopsy diagnoses.

Design.-The information system of a large women’s hospital serving an older than average population was searched over a 21 month period between July 1, 2005 and March 31, 2007 for HPV positive cases interpreted as ASC-US (Bethesda System 2001) utilizing computer-imaged LBC. Histologic diagnoses, patient ages, and presence or absence of an EC/TZS were analyzed. The average follow-up period was 7.5 months.

Results.- Among 4,273 women with HPV positive ASC-US results the cumulative cervical intraepithelial neoplasia 2 or 3 (CIN 2/3) and CIN 1 rates for 2,192 women with available biopsies were 5.1% and 43.6%, respectively. CIN2 /3 and CIN1 rates for women with HPV-positive ASC-US results were not significantly different for women with and without an EC/TZS.

Conclusions.- The risk of CIN2/3 in the study population was significantly lower than reported in widely cited trial data. Neither presence or absence of an EC/TZS nor the age of the patient had a statistically significant impact on the likelihood of biopsy diagnoses of CIN 2/3 and CIN1 in patients with HPV-positive ASC-US test results.

Table 2. Histologic Follow up Results in Women with Positive hrHPV and ASC-US TPPT Stratified by Age (10-Year Interval)

Age

F/U

No

CIN 2/3

CIN 1

No

(%)

95% CI

P*

No

(%)

%

P*

10-19

302

15

(5.0)

2.5-7.5

.94

121

(40.1)

34.6-45.6

.25

20-29

1268

69

(5.4)

4.2-6.6

.63

577

(45.5)

42.8-48.2

.27

30-39

352

16

(4.6)

2.4-6.8

.68

155

(44.0)

38.1-49.2

.87

40-49

176

8

(4.6)

1.5-7.7

.76

66

(37.5)

30.4-44.7

.12

50-59

75

3

(4.0)

0-8.4

>.99†

28

(37.3)

26.4-48.2

.28

60-69

19

0

.62†

8

(42.1)

19.9-64.3

.90

Total

2192

111

(5.1)

4.2-6.0

955

(43.6)

41.5-45.7

* P values were obtained by comparing each age group with total average %.

† Fisher’s exact test

hrHPV indicates high risk human papillomavirus; ASC-US, atypical squamous cells, undetermined significant; TPPT, ThinPrep Pap test; F/U, follow-up; CIN, cervical intraepithelial lesion, No, number.

Arch Pathol Lab Med. 2009. In press.

Follow-Up Findings in Women with HPV-Positive ASC-US Screening Test Results in a Large Womens Hospital Practice

Henry Armah MD, PhD; R. Marshall Austin MD; PhD, David Dabbs MD; Chengquan Zhao* MD

From the Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 15213

The authors have no relevant financial interest in the products or companies described in this article.

Presented orally at the 2008 USCAP Annual Meeting, Denver, Colorado. March 1 – March 7, 2008

Reprints: Chengquan Zhao MD, Department of Pathology, Magee-Womens Hospital of University of Pittsburgh Medical Center, 300 Halket Street, Pittsburgh, PA 15213 (e-mail: zhaoc@upmc.edu)

ABSTRACT

Context.- Reflex HPV testing has been designated in consensus guidelines as “preferred” for women with ASC-US liquid-based cytology (LBC) results, and colposcopy is currently recommended for patients with HPV-positive ASCUS results. Data from large clinical practices utilizing newer screening methods and current cytology terminology remain limited.

Objectives.-We analyzed data from patients with ASCUS LBC and positive HPV test results. We also assessed the impact of the presence or absence of an endocervical cell/transformation zone sample (EC/TZS) on biopsy diagnoses.

Design.-The information system of a large women’s hospital serving an older than average population was searched over a 21 month period between July 1, 2005 and March 31, 2007 for HPV positive cases interpreted as ASC-US (Bethesda System 2001) utilizing computer-imaged LBC. Histologic diagnoses, patient ages, and presence or absence of an EC/TZS were analyzed. The average follow-up period was 7.5 months.

Results.- Among 4,273 women with HPV positive ASC-US results the cumulative cervical intraepithelial neoplasia 2 or 3 (CIN 2/3) and CIN 1 rates for 2,192 women with available biopsies were 5.1% and 43.6%, respectively. CIN2 /3 and CIN1 rates for women with HPV-positive ASC-US results were not significantly different for women with and without an EC/TZS.

Conclusions.- The risk of CIN2/3 in the study population was significantly lower than reported in widely cited trial data. Neither presence or absence of an EC/TZS nor the age of the patient had a statistically significant impact on the likelihood of biopsy diagnoses of CIN 2/3 and CIN1 in patients with HPV-positive ASC-US test results.

Table 2. Histologic Follow up Results in Women with Positive hrHPV and ASC-US TPPT Stratified by Age (10-Year Interval)

Age

F/U

No

CIN 2/3

CIN 1

No

(%)

95% CI

P*

No

(%)

%

P*

10-19

302

15

(5.0)

2.5-7.5

.94

121

(40.1)

34.6-45.6

.25

20-29

1268

69

(5.4)

4.2-6.6

.63

577

(45.5)

42.8-48.2

.27

30-39

352

16

(4.6)

2.4-6.8

.68

155

(44.0)

38.1-49.2

.87

40-49

176

8

(4.6)

1.5-7.7

.76

66

(37.5)

30.4-44.7

.12

50-59

75

3

(4.0)

0-8.4

>.99†

28

(37.3)

26.4-48.2

.28

60-69

19

0

.62†

8

(42.1)

19.9-64.3

.90

Total

2192

111

(5.1)

4.2-6.0

955

(43.6)

41.5-45.7

* P values were obtained by comparing each age group with total average %.

† Fisher’s exact test

hrHPV indicates high risk human papillomavirus; ASC-US, atypical squamous cells, undetermined significant; TPPT, ThinPrep Pap test; F/U, follow-up; CIN, cervical intraepithelial lesion, No, number.

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13 楼发表于2009-06-12 22:34:00举报|引用
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本帖最后由于 2009-06-12 22:42:00 编辑

Arch Pathol Lab Med. 2009. In press.

Clinical Utility of Adjunctive High Risk HPV DNA Testing in Women with Pap Test findings of Atypical Glandular Cells

Zhao C, MD; Florea A, MD; Marshall Austin RM, MD, PhD.

From the Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 15213

The authors have no relevant financial interest in the products or companies described in this article.

Some of the data was presented as a poster at the USCAP Annual Meeting, Denver, Colorado. March, 2008

Reprints: Chengquan Zhao, MD, Department of Pathology, Magee-Womens Hospital University of Pittsburgh Medical Center, 300 Halket Street, Pittsburgh, PA 15213 (e-mail: zhaoc@upmc.edu)

Context.- Atypical glandular cell (AGC) Pap interpretations are challenging. Most biopsy findings are benign, but AGC results may also reflect highly significant noninvasive neoplastic and malignant histologic outcomes. High risk human papillomavirus (hrHPV) test use with AGC Pap results is evolving.

Objectives.- This study was conducted to further evaluate the utility and limitations of hrHPV testing with AGC Paps.
Design - Hospital records were searched for AGC Pap tests from 6/1/2005 to 8/31/2007. Cases of AGC with hrHPV test and histopathologic follow-up were included.

Results - 662 women with AGC Pap results and follow-up were analyzed; hrHPV results were available in 309 of 662 and were positive in 75. Among the 75 with hrHPV-positive AGC results, 13 had cervical intraepithelial neoplasia (CIN) 2/3, 10 had adenocarcinoma (AIS), and 3 had cervical invasive adenocarcinoma, whereas for 234 women with hrHPV-negative results, 1 had CIN 2/3, 1 had AIS, 1 each had cervical adenocarcinoma and ovarian carcinoma, and 8 had endometrial carcinoma.
Conclusions.- hrHPV-positive AGC results were most strongly associated with CIN2/3 and AIS in women younger than 50. hrHPV positive AGC results were also present in all three cases of invasive cervical adenocarcinoma in women under 50. Of note, hrHPV-negative AGC results were present in ten of thirteen (76.9%) of carcinomas detected after AGC Pap tests, all in women 40 or older- 8 endometrial adenocarcinomas, 1 ovarian carcinoma, and 1 cervical adenosquamous carcinoma in a woman in her 50s. hrHPV testing after AGC Pap findings was most helpful in detection of CIN2/3 and AIS and invasive cervical adenocarcinomas in women younger than 50.

Table 1.

Correlation of the AGC Subcategories for 309 Cases with hrHPV DNA testing and Histologic Diagnoses of Neoplastic or Malignant Lesions on Surgical Pathology Follow-up

Cytologic Result

AGC/ASC-US

(n=97)

AGC/ASC-H

(n=29)

AGC/HSIL

(n=4)

AGC-EM

(n=19)

AGC-EC

(n=75)

AGC-NOS

(n=85)

Total

(n=309)

Age (years)

45.1

(19-84)

41.5

(21-76)

34.4

(24-45)

52.2

(42-77)

38.7

(19-72)

46.3

(27-84)

43.9

(19-84)

Histologic

diagnosis

HPV+

n=17

(%)

HPV-

n=80

(%)

HPV+

n=12

(%)

HPV-

n=17

(%)

HPV+

n=3

(%)

HPV-

n=1

(%)

HPV+

n=1

(%)

HPV-

n=18

(%)

HPV+

n=28

(%)

HPV-

n=47

(%)

HPV+

n=14

(%)

HPV-

n=71

(%)

HPV+

n=75

(%)

HPV-

n=234

(%)

Squamous cell Cervical Intaepithelieal Neoplasia

10

(58.8)

10

(12.5)

4

(33.3)

5

(29.4)

3

(100)

1

(100)

0

1

(5.6)

15

(53.6)

12

(25.5)

7

(50.0)

3

(4.2)

39

(52.0)

32

(13.7)

CIN2/3

3*

2*

1

4*

2

13

1

CIN1

7

10

2

5

1

11

12

5

3

26

31

Glandular cell Cervical Neoplasia

1

(5.9)

0

2

(16.7)

1

(5.9)

1

(33.3)

0

7

(25.0)

0

2

(14.3)

0

13

(17.3)

1

(0.4)

Invasive

Cervical Carcinoma

1^‡

3

1

AIS

1*

2*

1*

4*

2

10

Endometrial Neoplasia

0

6

(7.5)

0

4

(22.2)

0

1

(2.1)

0

4

(5.6)

0

15

(6.4)

Endometrial

carcinoma

3

1

4

8^†

Endometrial

hyperplasia

3

1

7

Ovarian Neoplasia

0

1

(2.1)

0

1

(0.4)

Serous carcinoma

1

* One case with both CIN2,3 and AIS, total 4 cases with both CIN 2/3 and AIS
† Including 7 endometrioid ca, 1 papillary carcinoma.
‡ Adenosquamous carcinoma (older, HPV-).

Table 2

Age and Subsequent Significant Histologic Diagnoses in Women with AGC Paps and hrHPV Test Results

Histologic diagnoses

<40 years

≥40 to <50 years

≥50 years

Total

HPV+

(n=41)

HPV-

(n=64)

HPV+

(n=19)

HPV-

(n=108)

HPV+

(n=15)

HPV-

(n=62)

HPV+

(n=75)

HPV-

(n=234)

CIN2/3

10*

(24.4%)

1

(1.6%)

2^†

(10.5%)

0

1

(6.7%)

0

13

(17.3%)

1

(0.4%)

Invasive

carcinoma

2

(4.9%)

0

1

(5.3%)

0

1

(1.6%)

3

(4.0%)

1

(0.4%)

AIS

4*

(9.8%)

0

6^†

(31.6%)

0

10

(13.3%)

Endometrial carcinoma

0

2

(1.9%)

0

6

(9.7%)

0

8

(3.4%)

CAH

0

2

(1.9%)

0

3

(4.8%)

0

5

(2.1%)

Metastatic carcinoma

0

1

(0.9%)

0

1

(0.4%)

Total

13

(31.7%)

1

(1.6%)

8

(42.1%)

5

(4.6%)

1

(6.7%)

10

(16.1%)

22

(29.3%)

16

(6.8%)

* 3 cases with both AIS and CIN 2/3

† 1 case with both AIS and CIN 2/3

Total 4 cases with AIS and CIN 2/3, all HPV+

Arch Pathol Lab Med. 2009. In press.

Clinical Utility of Adjunctive High Risk HPV DNA Testing in Women with Pap Test findings of Atypical Glandular Cells

Zhao C, MD; Florea A, MD; Marshall Austin RM, MD, PhD.

From the Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 15213

The authors have no relevant financial interest in the products or companies described in this article.

Some of the data was presented as a poster at the USCAP Annual Meeting, Denver, Colorado. March, 2008

Reprints: Chengquan Zhao, MD, Department of Pathology, Magee-Womens Hospital University of Pittsburgh Medical Center, 300 Halket Street, Pittsburgh, PA 15213 (e-mail: zhaoc@upmc.edu)

Context.- Atypical glandular cell (AGC) Pap interpretations are challenging. Most biopsy findings are benign, but AGC results may also reflect highly significant noninvasive neoplastic and malignant histologic outcomes. High risk human papillomavirus (hrHPV) test use with AGC Pap results is evolving.

Objectives.- This study was conducted to further evaluate the utility and limitations of hrHPV testing with AGC Paps.
Design - Hospital records were searched for AGC Pap tests from 6/1/2005 to 8/31/2007. Cases of AGC with hrHPV test and histopathologic follow-up were included.

Results - 662 women with AGC Pap results and follow-up were analyzed; hrHPV results were available in 309 of 662 and were positive in 75. Among the 75 with hrHPV-positive AGC results, 13 had cervical intraepithelial neoplasia (CIN) 2/3, 10 had adenocarcinoma (AIS), and 3 had cervical invasive adenocarcinoma, whereas for 234 women with hrHPV-negative results, 1 had CIN 2/3, 1 had AIS, 1 each had cervical adenocarcinoma and ovarian carcinoma, and 8 had endometrial carcinoma.
Conclusions.- hrHPV-positive AGC results were most strongly associated with CIN2/3 and AIS in women younger than 50. hrHPV positive AGC results were also present in all three cases of invasive cervical adenocarcinoma in women under 50. Of note, hrHPV-negative AGC results were present in ten of thirteen (76.9%) of carcinomas detected after AGC Pap tests, all in women 40 or older- 8 endometrial adenocarcinomas, 1 ovarian carcinoma, and 1 cervical adenosquamous carcinoma in a woman in her 50s. hrHPV testing after AGC Pap findings was most helpful in detection of CIN2/3 and AIS and invasive cervical adenocarcinomas in women younger than 50.

Table 1.

Correlation of the AGC Subcategories for 309 Cases with hrHPV DNA testing and Histologic Diagnoses of Neoplastic or Malignant Lesions on Surgical Pathology Follow-up

Cytologic Result

AGC/ASC-US

(n=97)

AGC/ASC-H

(n=29)

AGC/HSIL

(n=4)

AGC-EM

(n=19)

AGC-EC

(n=75)

AGC-NOS

(n=85)

Total

(n=309)

Age (years)

45.1

(19-84)

41.5

(21-76)

34.4

(24-45)

52.2

(42-77)

38.7

(19-72)

46.3

(27-84)

43.9

(19-84)

Histologic

diagnosis

HPV+

n=17

(%)

HPV-

n=80

(%)

HPV+

n=12

(%)

HPV-

n=17

(%)

HPV+

n=3

(%)

HPV-

n=1

(%)

HPV+

n=1

(%)

HPV-

n=18

(%)

HPV+

n=28

(%)

HPV-

n=47

(%)

HPV+

n=14

(%)

HPV-

n=71

(%)

HPV+

n=75

(%)

HPV-

n=234

(%)

Squamous cell Cervical Intaepithelieal Neoplasia

10

(58.8)

10

(12.5)

4

(33.3)

5

(29.4)

3

(100)

1

(100)

0

1

(5.6)

15

(53.6)

12

(25.5)

7

(50.0)

3

(4.2)

39

(52.0)

32

(13.7)

CIN2/3

3*

2*

1

4*

2

13

1

CIN1

7

10

2

5

1

11

12

5

3

26

31

Glandular cell Cervical Neoplasia

1

(5.9)

0

2

(16.7)

1

(5.9)

1

(33.3)

0

7

(25.0)

0

2

(14.3)

0

13

(17.3)

1

(0.4)

Invasive

Cervical Carcinoma

1^‡

3

1

AIS

1*

2*

1*

4*

2

10

Endometrial Neoplasia

0

6

(7.5)

0

4

(22.2)

0

1

(2.1)

0

4

(5.6)

0

15

(6.4)

Endometrial

carcinoma

3

1

4

8^†

Endometrial

hyperplasia

3

1

7

Ovarian Neoplasia

0

1

(2.1)

0

1

(0.4)

Serous carcinoma

1

* One case with both CIN2,3 and AIS, total 4 cases with both CIN 2/3 and AIS
† Including 7 endometrioid ca, 1 papillary carcinoma.
‡ Adenosquamous carcinoma (older, HPV-).

Table 2

Age and Subsequent Significant Histologic Diagnoses in Women with AGC Paps and hrHPV Test Results

Histologic diagnoses

<40 years

≥40 to <50 years

≥50 years

Total

HPV+

(n=41)

HPV-

(n=64)

HPV+

(n=19)

HPV-

(n=108)

HPV+

(n=15)

HPV-

(n=62)

HPV+

(n=75)

HPV-

(n=234)

CIN2/3

10*

(24.4%)

1

(1.6%)

2^†

(10.5%)

0

1

(6.7%)

0

13

(17.3%)

1

(0.4%)

Invasive

carcinoma

2

(4.9%)

0

1

(5.3%)

0

1

(1.6%)

3

(4.0%)

1

(0.4%)

AIS

4*

(9.8%)

0

6^†

(31.6%)

0

10

(13.3%)

Endometrial carcinoma

0

2

(1.9%)

0

6

(9.7%)

0

8

(3.4%)

CAH

0

2

(1.9%)

0

3

(4.8%)

0

5

(2.1%)

Metastatic carcinoma

0

1

(0.9%)

0

1

(0.4%)

Total

13

(31.7%)

1

(1.6%)

8

(42.1%)

5

(4.6%)

1

(6.7%)

10

(16.1%)

22

(29.3%)

16

(6.8%)

* 3 cases with both AIS and CIN 2/3

† 1 case with both AIS and CIN 2/3

Total 4 cases with AIS and CIN 2/3, all HPV+

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Table 6.

Accumulated Data on ASC-H Prevalence in Women with LBC Pap Test (Literature review)

Total No.	Positive No.	%	Reference
10745	36	0.34	Lee⁴
107021	257	0.24	Taraif⁵
20354	222	1.09	Geisinger⁶
29475	60	0.22	Gupta⁷
83667	488	0.58	McHale⁸
119659	377	0.32	Wu⁹
60390	414	0.69	Duncan¹⁰
30658	96	0.31	Srodon¹¹
76675	223	0.29	Stany¹²
152495	800	0.52	Saad¹³
9214	25	0.27	Selvaggi¹⁴
77979	255	0.33	Shidham¹⁵
778332	3253	0.42	In total
270,338	1,619	0.60	Current study
122 Lab, Mean (ThinPrep Pap)		0.57	Davey¹⁷

ASC-H indicates atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion; LBC, liquid-based cytology; Lab, laboratories.

Table 7.

Accumulated Data on HC2 hrHPV Positive Rates in Women with ASC-H LBC Results and Histopathological Follow-up (Literature Review)

hrHPV test

Histologic CIN 2/3

Panel review/

Reclassi-

fication

Year of publica

-tion

Reference

hrHPV positive

hrHPV negative

Tested No.

Positive

No.

%

Tested No.

CIN 2/3

No.

%

Tested No.

CIN 2/3

No.

%

23

17

73.9

yes

2005

Duncan¹⁰

110

92

83.6

92

54

58.7

18

2

11.1

yes

2001

2006

Sherman^{2, 18}

48

38

79.2

38

22

57.9

10

0

0

yes

2005

Liman¹⁹

101

82

81.2

33

16

48.5

9

0

0

yes

2007

Nguyen³³

96

64

66.7

45

18

40.0

12

1

4.5

no

2006

Srodon¹¹

95

54

56.8

31

13

41.9

13

1

7.7

no

2007

Reid²⁰

88

59

67.0

35

15

42.9

7

0

0

no

2006

Wu⁹

16

6

37.5

no

2004

Rowe²¹

48

16

33.3

10

3

30.0

6

0

0

no

2005

Palma²²

33

21

63.6

15

4

26.7

4

0

0

no

2006

Chivukula²⁴

73

43

58.9

43

14

32.6

30

1

3.3

no

2007

Owens²⁵

109

58

53.2

58

19

32.8

51

1

2.0

no

2007

You²⁶

88

60

68.2

60

15

25.0

28

0

0

no

2004

El-Fakhara ²⁸

40

21

52.5

21

11

52.4

13

1

7.7

no

2004

Hoschar ²⁹

257

151

58.8

87

33

37.9

no

2005

Taraif ⁵

187

86

46.0

no

2006

O’Brien³⁰

209

105

50.2

no

2007

Howard³¹

138

53

38.4

36

11

30.6

45

2

4.4

no

2006

Christal³²

115

54

47.0

54

23

42.6

19

4

21.1

no

2007

Sullivan³⁴

1874

1080

57.6

658

271

41.2

265

13

4.9

In total

1187

589

49.6

257

84

32.7

248

3

1.2

no

2008

Current

hrHPV indicates high risk human papillomavirus; HC 2, Hybrid Capture 2; ASC-H, atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion; TPPT, ThinPrep Pap tests; CIN 1, cervical intraepithelial neoplasm 1; CIN 2/3, cervical intraepithelial neoplasm 2 or 3; F/U, follow-up; LBC, liquid-based cytology.

Table 6.

Accumulated Data on ASC-H Prevalence in Women with LBC Pap Test (Literature review)

Total No.	Positive No.	%	Reference
10745	36	0.34	Lee⁴
107021	257	0.24	Taraif⁵
20354	222	1.09	Geisinger⁶
29475	60	0.22	Gupta⁷
83667	488	0.58	McHale⁸
119659	377	0.32	Wu⁹
60390	414	0.69	Duncan¹⁰
30658	96	0.31	Srodon¹¹
76675	223	0.29	Stany¹²
152495	800	0.52	Saad¹³
9214	25	0.27	Selvaggi¹⁴
77979	255	0.33	Shidham¹⁵
778332	3253	0.42	In total
270,338	1,619	0.60	Current study
122 Lab, Mean (ThinPrep Pap)		0.57	Davey¹⁷

ASC-H indicates atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion; LBC, liquid-based cytology; Lab, laboratories.

Table 7.

Accumulated Data on HC2 hrHPV Positive Rates in Women with ASC-H LBC Results and Histopathological Follow-up (Literature Review)

hrHPV test

Histologic CIN 2/3

Panel review/

Reclassi-

fication

Year of publica

-tion

Reference

hrHPV positive

hrHPV negative

Tested No.

Positive

No.

%

Tested No.

CIN 2/3

No.

%

Tested No.

CIN 2/3

No.

%

23

17

73.9

yes

2005

Duncan¹⁰

110

92

83.6

92

54

58.7

18

2

11.1

yes

2001

2006

Sherman^{2, 18}

48

38

79.2

38

22

57.9

10

0

0

yes

2005

Liman¹⁹

101

82

81.2

33

16

48.5

9

0

0

yes

2007

Nguyen³³

96

64

66.7

45

18

40.0

12

1

4.5

no

2006

Srodon¹¹

95

54

56.8

31

13

41.9

13

1

7.7

no

2007

Reid²⁰

88

59

67.0

35

15

42.9

7

0

0

no

2006

Wu⁹

16

6

37.5

no

2004

Rowe²¹

48

16

33.3

10

3

30.0

6

0

0

no

2005

Palma²²

33

21

63.6

15

4

26.7

4

0

0

no

2006

Chivukula²⁴

73

43

58.9

43

14

32.6

30

1

3.3

no

2007

Owens²⁵

109

58

53.2

58

19

32.8

51

1

2.0

no

2007

You²⁶

88

60

68.2

60

15

25.0

28

0

0

no

2004

El-Fakhara ²⁸

40

21

52.5

21

11

52.4

13

1

7.7

no

2004

Hoschar ²⁹

257

151

58.8

87

33

37.9

no

2005

Taraif ⁵

187

86

46.0

no

2006

O’Brien³⁰

209

105

50.2

no

2007

Howard³¹

138

53

38.4

36

11

30.6

45

2

4.4

no

2006

Christal³²

115

54

47.0

54

23

42.6

19

4

21.1

no

2007

Sullivan³⁴

1874

1080

57.6

658

271

41.2

265

13

4.9

In total

1187

589

49.6

257

84

32.7

248

3

1.2

no

2008

Current

hrHPV indicates high risk human papillomavirus; HC 2, Hybrid Capture 2; ASC-H, atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion; TPPT, ThinPrep Pap tests; CIN 1, cervical intraepithelial neoplasm 1; CIN 2/3, cervical intraepithelial neoplasm 2 or 3; F/U, follow-up; LBC, liquid-based cytology.

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Table 2.

hrHPV Prevalence in Older and Younger Women with ASC-H TPPT (Two Age Groups)

Age groups

hrHPV tested

Positive

%

95% CI

P value

<30

556

340

61.2

57.1-65.3

<.001

≥30

631

249

39.5

35.7-43.3

<40

858

469

54.7

51.4-58.0

<.001

≥40

329

120

36.5

31.3-41.7

hrHPV indicates high risk human papillomavirus; ASC-H, atypical squamous cells, cannot exclude high- grade squamous intraepithelial lesion; TPPT, ThinPrep Pap tests.

Table 3.

Histologic Follow-up Results in Women with ASC-H Comparing hrHPV Positive and Negative Groups Stratified by Ages

Age

hrHPV Positive

hrHPV Negative

P value

(CIN 2/3)

P value

(CIN 1)

F/U No.

CIN 2/3

(%)

CIN 1

(%)

F/U No.

CIN 2/3

(%)

CIN 1

(%)

10-19

19

2

(10.5)

6

(31.6)

5

0

20-29

118

40

(33.9)

37

(31.4)

79

0

19

(24.1)

<.001

0.27

30-39

67

31

(46.3)

18

(26.9)

73

3

(4.1)

7

(9.6)

<.001

.008

40-49

33

8

(24.2)

10

(30.3)

52

0

2

(3.8)

<.001*

.001*

50-59

12

3

(25.0)

4

(33.3)

21

0

4

(19.0)

60-69

6

0

1

(16.7)

10

0

70-79

2

0

8

0

257

84

(32.7)

76

(29.2)

248

3

(1.2)

32

(12.9)

<.001

*Fisher’s exact test

hrHPV indicates high risk human papillomavirus; ASC-H, atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion; TPPT, ThinPrep Pap tests; CIN 1, cervical intraepithelial neoplasm 1; CIN 2/3,cervical intraepithelial neoplasm 2 or 3; F/U, follow-up.

Table 4.

Histologic Follow-up Results Comparing Women with ASC-H TPPT Age 40 and Older with Younger Women

Age groups

F/U

No.

CIN 2/3

CIN 1

No.

%

95% CI

P value

No.

%

95% CI

P value

<40

361

76

21.1

16.9-25.3

<.001

87

24.1

19.7-28.5

.019

≥40

144

11

7.6

3.3-11.9

21

14.6

8.8-20.4

Total

505

87

17.2

13.9-20.5

108

21.4

17.8-25.0

ASC-H indicates atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion; TPPT, ThinPrep Pap tests; CIN 1, cervical intraepithelial neoplasm 1; CIN 2/3, cervical intraepithelial neoplasm 2 or 3; F/U, follow-up.

Table 5.

Histologic Follow-up Results in Women with ASC-H TPPT with and without EC/TZS

EC/TZS Present

EC/TZS Absent

P value

Total No.

CIN 2-3

(%)

CIN 1

(%)

Total No.

CIN 2/3

(%)

CIN 1

(%)

CIN 2/3

CIN 1

<30

203

38

(18.7)

54

(26.6)

18

4

(22.2)

8

(44.4)

.75

.11

≥30

267

41

(15.4)

43

(16.1)

17

4

(23.5)

3

(17.6)

.37

.74*

Total

470

79

(16.8)

97

(20.6)

35

8

(22.9)

11

(31.4)

.36

.13

*Fisher’s exact test.

ASC-H indicates atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion; TPPT, ThinPrep Pap tests; EC/TZS, endocervical/transformation zone sample; CIN 1, cervical intraepithelial neoplasm 1; CIN 2/3, cervical intraepithelial neoplasm 2 or 3; F/U, follow-up.

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Table 1.

hrHPV Prevalence in Women with ASC-H TPPT with and without TZ/ECS

(10 Year Interval)

Age

Total

EC/TZS present

EC/TZS absent

P value

hrHPV tested

Positive

%

95% CI

hrHPV tested

Positive

%

hrHPV tested

Positive

%

10-19

68

56

82.4

73.3-91.5

64

52

81.3

4

100.0

>.99*

20-29

488

284

58.2

53.8-62.6

453

263

58.1

35

21

60.0

.86

30-39

302

129

42.7

37.1-48.3

282

118

41.8

20

11

55.0

.35

40-49

195

68

34.9

28.2-41.6

184

64

34.8

11

4

36.4

.92

50-59

89

36

40.4

30.2-50.6

75

29

38.7

14

7

50.0

.43

60-69

30

13

43.3

25.6-61.0

26

11

42.3

4

2

50.0

>.99*

70-79

15

3

20.0

0-

40.2

15

3

20.0

0

Total

1187

589

49.6

46.8-52.4

1099

540

49.1

88

49

55.7

.24

*Fisher’s exact test

EC/TZS indicates endocervical/transformation zone sample; hrHPV, high risk human papillomavirus; ASC-H, atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion; TPPT, ThinPrep Pap tests

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本帖最后由于 2009-06-28 13:15:00 编辑 Arch Pathol Lab Med.

Erratum in:: Arch Pathol Lab Med. 2009 Feb;133(2):175.

Adjunctive human papillomavirus DNA testing is a useful option in some clinical settings for disease risk assessment and triage of females with ASC-H Papanicolaou test results.（在巴氏结果为ASC-H的女性辅助HPV-DNA检测在一些临床疾病的风险评估和分流的作用）

Bandyopadhyay S, Austin RM, Dabbs D, Zhao C.

Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.

CONTEXT: Recent guidelines recommend colposcopy for women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). objective: To determine whether adjunctive high-risk human papillomavirus (hrHPV) testing is useful for disease risk assessment in females with ASC-H Papanicolaou (Pap) test results. DESIGN: High-risk HPV prevalence and histopathologic follow-up data on 1187 females with ASC-H ThinPrep Pap test (TPPT) and hrHPV test results were analyzed. RESULTS: ASC-H was reported in 1646 (0.59%) [corrected] of 277 400 (270 338 TPPT and 7062 conventional) Pap test results. The difference in ASC-H detection rates between TPPTs and conventional Pap smears was statistically significant (0.60% vs 0.38%; P = .02). High-risk HPV was detected in 589 (49.6%) of 1187 females with ASC-H TPPT and hrHPV testing. The hrHPV DNA-positive rate in females younger than 40 years was 54.7%, significantly higher than the 36.5% in women 40 years and older. Among 505 females with histopathologic follow-up, cervical intraepithelial neoplasia 2/3 was identified in 32.7% of hrHPV-positive females compared with 1.2% in hrHPV-negative females. The sensitivity, specificity, positive predictive value, and negative predictive value of ASC-H cytology in conjunction with hrHPV DNA testing results for detection of cervical intraepithelial neoplasia 2/3 were 96.1% versus 100.0%, 54.0% versus 68.4%, 35.8% versus 20.8%, and 98.1% versus 100.0% in females younger than 40 years and women 40 years and older, respectively. CONCLUSIONS: Our data suggest that reflex hrHPV testing is a highly useful option for women with ASC-H Pap tests. Females with ASC-H and negative hrHPV testing may be more efficiently managed by follow-up with regular Pap and hrHPV testing rather than universal colposcopy, especially for women 40 years and older.（结论：我们的数据表明：对巴氏结果为ASC-H的女性进行高危HPV检测的结果反馈证明是非常有用的。巴氏结果为ASC-H而高危HPV检测结果为阴性的女性通过规则的巴氏筛查和高危HPV检测比普通的阴道镜可更有效的管理；特别是对40岁及以上的女性。）

Arch Pathol Lab Med. 2008 Dec;132(12):1874-81.

Erratum in:: Arch Pathol Lab Med. 2009 Feb;133(2):175.

Adjunctive human papillomavirus DNA testing is a useful option in some clinical settings for disease risk assessment and triage of females with ASC-H Papanicolaou test results.（在巴氏结果为ASC-H的女性辅助HPV-DNA检测在一些临床疾病的风险评估和分流的作用）

Bandyopadhyay S, Austin RM, Dabbs D, Zhao C.

Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.

CONTEXT: Recent guidelines recommend colposcopy for women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). objective: To determine whether adjunctive high-risk human papillomavirus (hrHPV) testing is useful for disease risk assessment in females with ASC-H Papanicolaou (Pap) test results. DESIGN: High-risk HPV prevalence and histopathologic follow-up data on 1187 females with ASC-H ThinPrep Pap test (TPPT) and hrHPV test results were analyzed. RESULTS: ASC-H was reported in 1646 (0.59%) [corrected] of 277 400 (270 338 TPPT and 7062 conventional) Pap test results. The difference in ASC-H detection rates between TPPTs and conventional Pap smears was statistically significant (0.60% vs 0.38%; P = .02). High-risk HPV was detected in 589 (49.6%) of 1187 females with ASC-H TPPT and hrHPV testing. The hrHPV DNA-positive rate in females younger than 40 years was 54.7%, significantly higher than the 36.5% in women 40 years and older. Among 505 females with histopathologic follow-up, cervical intraepithelial neoplasia 2/3 was identified in 32.7% of hrHPV-positive females compared with 1.2% in hrHPV-negative females. The sensitivity, specificity, positive predictive value, and negative predictive value of ASC-H cytology in conjunction with hrHPV DNA testing results for detection of cervical intraepithelial neoplasia 2/3 were 96.1% versus 100.0%, 54.0% versus 68.4%, 35.8% versus 20.8%, and 98.1% versus 100.0% in females younger than 40 years and women 40 years and older, respectively. CONCLUSIONS: Our data suggest that reflex hrHPV testing is a highly useful option for women with ASC-H Pap tests. Females with ASC-H and negative hrHPV testing may be more efficiently managed by follow-up with regular Pap and hrHPV testing rather than universal colposcopy, especially for women 40 years and older.（结论：我们的数据表明：对巴氏结果为ASC-H的女性进行高危HPV检测的结果反馈证明是非常有用的。巴氏结果为ASC-H而高危HPV检测结果为阴性的女性通过规则的巴氏筛查和高危HPV检测比普通的阴道镜可更有效的管理；特别是对40岁及以上的女性。）

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18 楼发表于2009-06-12 22:20:00举报|引用
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Table 1

Correlation of the Sub-Categories of 460 AGC Cases with Preneoplastic or Neoplastic Lesions in Tissue Biopsies

AGC & ASC-US

(n=68)

AGC-EM

(n=36)

AGC-NOS

(n=187)

AGC-EC

(n=169)

Total

(n=460)

Squamous cell lesions

9 (13.2%)

1 (2.8%)

6 (3.2%)

10 (5.9%)

26 (5.7%)

Invasive squamous

carcinoma

1 (0.6%)

1 (0.2%)

CIN 2,3

9 (13.2%)

1 (2.8%)

6 (3.2%)

9 (5.3%)

25 (5.4%)

Cervical glandular lesions

0

5 (2.7%)

14 (8.3%)

19 (4.1%)

AIS

1 (0.5%)

4 (2.4%)

5 (1.1%)

Invasive carcinoma

4 (2.1%)

9*(5.3%)

13(2.8%)

MMMT

1 (0.6%)

1 (0.2%)

Endometrial lesions

3 (4.4%)

19 (52.8%)

30 (16.0%)

2 (1.2%)

54 (11.7%)

Atypical complex hyperplasia

3 (4.4%)

8 (22.2%)

8 (4.3%)

1 (0.6%)

20 (4.3%)

Endometrioid carcinoma

10 (27.8%)

19 (10.2%)

1 (0.6%)

30 (6.5%)

MMMT

1 (2.8%)

1 (0.5%)

2 (0.4%)

Complete mole

1 (0.5%)

1 (0.2%)

Choriocarcinoma

1 (0.5%)

1 (0.2%)

Ovarian lesions

0

1 (2.8%)

4 (2.1%)

1 (0.6%)

6 (1.3%)

Serous carcinoma

1 (2.8%)

2 (1.1%)

1 (0.6%)

4 (0.9%)

Endometrioid carcinoma

1 (0.5%)

1 (0.2%)

Clear cell carcinoma

1 (0.5%)

1 (0.2%)

Total

12 (17.6%)

21 (58.3%)

45 (24.1%)

27 (16.0%)

105 (22.8%)

AGC, atypical glandular cells; ASC-US, atypical squamous cells of undetermined significance; AGC-EM, atypical glandular cells, endometrial origin; AGC-EC, atypical glandular cells, endocervical origin; AGC-NOS, atypical glandular cells, not otherwise specified; CIN, cervical intraepithelial neoplasia; MMMT, malignant müllerian mixed tumor; AIS, adenocarcinoma in situ.

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19 楼发表于2009-06-12 22:20:00举报|引用
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Table 2

The Relation of Age and Subsequent Significant Histologic Diagnosis in Women with AGC Paps

	<35 (n=80)	35-50 (n=262)	>50 (n=118)	Total (n=460)
CIN 2,3 or above	8 (10.0%)	11 (4.2%)	7(5.9%)	26 (5.7%)
AIS	2 (2.5%)	2 (0.8%)	1 (0.8%)	5 (1.1%)
Endocervical invasive tumor	0	5 (1.9%)	9 (7.7%)	14* (3.0%)
ACH	0	13 (5.0%)	7 (5.9%)	20 (4.3%)
Endometrial malignancy	0	9 (3.4%)	24 (20.3%)	33† (7.2%)
Ovarian carcinoma	0	2 (0.8%)	4 (3.4%)	6 (1.3%)
Complete mole	1 (1.2%)	0	0	1 (0.2%)
Total lesions	11 (13.8%)	42 (16.0%)	52 (45.8%)	105 (22.8%)

AGC, atypical glandular cells; CIN, cervical intraepithelial neoplasia; AIS, adenocarcinoma in situ; ACH, atypical complex hyperplasia.

* Including 13 cases of invasive endocervical carcinoma and one case of malignant müllerian mixed tumor.

† Including 30 cases of endometrioid carcinoma, 2 cases of malignant müllerian mixed tumor, and one case of choriocarcinoma.

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20 楼发表于2009-06-12 22:15:00举报|引用
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本帖最后由于 2009-06-28 12:51:00 编辑 Acta Cytol. 2009 Mar-Apr;53(2):153-9.

Clinical significance of atypical glandular cells in conventional pap smears in a large, high-risk U.S. west coast minority population.(在一个大型、高危的美国西海岸少数民族人群中传统巴氏涂片为AGC的临床意义)

Zhao C, Austin RM, Pan J, Barr N, Martin SE, Raza A, Cobb C.

Department of Pathology, Los Angeles County and University of Southern California Medical Center, USA. zhaoc@upmc.edu

OBJECTIVE: To determine the incidence of clinically significant lesions on subsequent histologic follow-up in high-risk, predominantly minority patients with atypical glandular cells (AGC). STUDY DESIGN: A retrospective study was done on conventional Pap smears diagnosed as AGC of endocervical origin (AGC-EC), AGC of endometrial origin (AGC-EM) and AGC not otherwise specified (AGC-NOS) between January 1, 2003, and December 31, 2005. Histologic diagnoses were correlated with cytologic diagnoses. RESULT: Confirmed AGC cases were divided into 4 categories: 187 AGC-NOS, 169 AGC-EC, 68 AGC and atypical squamous cells of undetermined significance (ASCUS) and 36 AGC-EM. A total of 105 patients (22.8%) had significant precancerous (cervical intraepithelial neoplasia [CIN] 2/3, adenocarcinoma in situ [AIS]) or malignant (carcinoma) histologic outcomes. CIN 2/3 was the most common significant histologic outcome in women with AGC and ASCUS and patients <35 years with AGC. Endometrial neoplasia was the most common significant outcome in women with AGC-NOS and AGC-EM Pap results and in AGC patients > or =35. In women with AGC-EC Pap results, glandular cervical neoplasia occurred in 8.3% and CIN 2/3 in 5.9% offollow-up biopsies. CONCLUSION: AGC subtype and age significantly affect the probability of precancerous and malignant follow-up findings and anatomic site of neoplastic lesions. Access to newer screening technologies such as high-risk HPVDNA testing and liquid-based cytology will likely benefit such high-risk populations.（结论：在癌前病变和肿瘤的随访中发现，AGC的亚型、病人的年龄和肿瘤病灶解剖部位的可能性影响。进行新的筛查技术比如高危HPV检测和液基细胞学检测会使这种高危人群收益。）

Acta Cytol. 2009 Mar-Apr;53(2):153-9.

Clinical significance of atypical glandular cells in conventional pap smears in a large, high-risk U.S. west coast minority population.(在一个大型、高危的美国西海岸少数民族人群中传统巴氏涂片为AGC的临床意义)

Zhao C, Austin RM, Pan J, Barr N, Martin SE, Raza A, Cobb C.

Department of Pathology, Los Angeles County and University of Southern California Medical Center, USA. zhaoc@upmc.edu

OBJECTIVE: To determine the incidence of clinically significant lesions on subsequent histologic follow-up in high-risk, predominantly minority patients with atypical glandular cells (AGC). STUDY DESIGN: A retrospective study was done on conventional Pap smears diagnosed as AGC of endocervical origin (AGC-EC), AGC of endometrial origin (AGC-EM) and AGC not otherwise specified (AGC-NOS) between January 1, 2003, and December 31, 2005. Histologic diagnoses were correlated with cytologic diagnoses. RESULT: Confirmed AGC cases were divided into 4 categories: 187 AGC-NOS, 169 AGC-EC, 68 AGC and atypical squamous cells of undetermined significance (ASCUS) and 36 AGC-EM. A total of 105 patients (22.8%) had significant precancerous (cervical intraepithelial neoplasia [CIN] 2/3, adenocarcinoma in situ [AIS]) or malignant (carcinoma) histologic outcomes. CIN 2/3 was the most common significant histologic outcome in women with AGC and ASCUS and patients <35 years with AGC. Endometrial neoplasia was the most common significant outcome in women with AGC-NOS and AGC-EM Pap results and in AGC patients > or =35. In women with AGC-EC Pap results, glandular cervical neoplasia occurred in 8.3% and CIN 2/3 in 5.9% offollow-up biopsies. CONCLUSION: AGC subtype and age significantly affect the probability of precancerous and malignant follow-up findings and anatomic site of neoplastic lesions. Access to newer screening technologies such as high-risk HPVDNA testing and liquid-based cytology will likely benefit such high-risk populations.（结论：在癌前病变和肿瘤的随访中发现，AGC的亚型、病人的年龄和肿瘤病灶解剖部位的可能性影响。进行新的筛查技术比如高危HPV检测和液基细胞学检测会使这种高危人群收益。）

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Age	F/U No	CIN 2/3			CIN 1
Age	F/U No	No (%)	95% CI	P*		No (%)	%	P*
10-19	302	15 (5.0)	2.5-7.5	.94		121 (40.1)	34.6-45.6	.25
20-29	1268	69 (5.4)	4.2-6.6	.63		577 (45.5)	42.8-48.2	.27
30-39	352	16 (4.6)	2.4-6.8	.68		155 (44.0)	38.1-49.2	.87
40-49	176	8 (4.6)	1.5-7.7	.76		66 (37.5)	30.4-44.7	.12
50-59	75	3 (4.0)	0-8.4	>.99†		28 (37.3)	26.4-48.2	.28
60-69	19	0		.62†		8 (42.1)	19.9-64.3	.90
Total	2192	111 (5.1)	4.2-6.0			955 (43.6)	41.5-45.7