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1 楼发表于2009-11-14 22:32:00举报|引用
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学习，多谢！！

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本帖最后由于 2009-06-14 12:51:00 编辑 Gynecol Oncol. 2009 Jun 6. [Epub ahead of print]

Histologic follow-up results in 662 patients with Pap test findings of atypical glandular cells: Results from a large academic womens hospital laboratory employing sensitive screening methods.

Zhao C, Florea A, Onisko A, Austin RM.

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

OBJECTIVE: Atypical glandular cell (AGC) Pap interpretations and screening for glandular neoplasias remain major challenges. We document the largest reported AGC histopathologic follow-up experience and include verification bias-adjusted data on laboratory screening sensitivity. METHODS: AGC Pap tests of endocervical origin (AGC-EC), endometrial origin (AGC-EM), and not otherwise specified (AGC-NOS) were documented at a center serving an older low risk population. 98% of Pap tests were liquid-based cytology (LBC) specimens screened using computer-assisted screening. Follow-up diagnoses were correlated with cytology and stratified into age groups. Screening sensitivity was assessed by examining Pap results during 1 year preceding neoplastic diagnoses. Verification bias was adjusted with findings in over 2000 patients with hysterectomies. RESULTS: Of 247,131 Pap tests, 1021 (0.41%) reported AGC results and 662 cases had tissue follow-up. Precancerous or malignant neoplastic histologic outcomes were documented in 101 patients (15.3%), including 8.3% cervical, 6.3% endometrial, and 0.6% ovarian. AGC results were most often associated with neoplastic cervical outcomes in women younger than 40 and with neoplastic endometrial outcomes in women 50 or older. AGC-NOS with a squamous cell abnormality and AGC-EC results suggested cervical neoplasia, while AGC-EM results suggested endometrial neoplasia. CONCLUSIONS: AGC Pap results detected significant numbers of cervical and non-cervical neoplasias. Since 38 of 44 (86%) of AGC-detected carcinomas were endometrial or ovarian, HPV co-testing would not have aided screening in detecting the majority of malignancies diagnosed after AGC Pap results. Verification bias-adjusted Pap screening sensitivity in the laboratory for detection of significant neoplastic cervical disease was 93%.

宫颈涂片发现不典型腺细胞的662例病人的组织学随访：结果来源于应用敏感筛查方法的一大型妇产教学医院

目的：宫颈涂片中发现的不典型腺细胞(AGC)的解释及其对腺体肿瘤的筛查作用是目前存在的难点，因此我们对大量的AGC病例进行了组织学随访并对实验室筛查结果的灵敏性进行了误差校对（verification bias-adjusted ？）。

方法：将宫颈涂片中的AGC-EC(不典型腺细胞-来源于宫颈)，AGC-EM(不典型腺细胞-来源于子宫内膜)，AGC-NOS(不典型腺细胞-来源不明确)列入统计范围，数据来源于主要服务对象是老年低危人群的一医疗中心。98%的宫颈涂片使用的是液基细胞学计算机辅助筛查系统，根据细胞学结果又将随访诊断结果和年龄进行了分组。根据一年后组织学诊断结果对筛查的灵敏性进行了评估，根据超过2000例子宫切除病人的结果进了误差校对（Verification bias was adjusted with findings in over 2000 patients with hysterectomies？）

结果：在247,131例宫颈涂片中，1021 (0.41%)例报告了AGC，对其中的662例进行了组织学随访，发现癌前病变和恶性肿瘤病人101(15.3%)例，其中宫颈占 8.3%,子宫内膜占 6.3% ,卵巢占0.6%. 年龄小于40岁者发现的AGC多与宫颈肿瘤相关，年龄大于等于50岁者发现的AGC多与子宫内膜肿瘤相关，AGC-NOS伴有磷状上皮异常或AGC-EC多提示宫颈肿瘤，而AGC-EM多提示子宫内膜肿瘤。

结论：宫颈涂片发现AGC的病人中有相当部份病人有宫颈或非宫颈的肿瘤。在非典型腺细胞中随访中确认为癌的44例病人中38例(86%)属于子宫内膜癌或卵巢癌，因此宫颈涂片发现AGC随后的HPV基因检测对于发现大多数的恶性肿瘤来说并无帮助。该实验室对宫颈肿瘤检测经过误差校对后的灵敏性是93%。（Verification bias-adjusted Pap screening sensitivity in the laboratory for detection of significant neoplastic cervical disease was 93%.）

(laurelshihxbl 翻译，注：红色部份翻译是否确切，请赵老师和诸位指点，主要是对verification bias-adjusted的中文不太熟悉)

Gynecol Oncol. 2009 Jun 6. [Epub ahead of print]

Histologic follow-up results in 662 patients with Pap test findings of atypical glandular cells: Results from a large academic womens hospital laboratory employing sensitive screening methods.

Zhao C, Florea A, Onisko A, Austin RM.

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

OBJECTIVE: Atypical glandular cell (AGC) Pap interpretations and screening for glandular neoplasias remain major challenges. We document the largest reported AGC histopathologic follow-up experience and include verification bias-adjusted data on laboratory screening sensitivity. METHODS: AGC Pap tests of endocervical origin (AGC-EC), endometrial origin (AGC-EM), and not otherwise specified (AGC-NOS) were documented at a center serving an older low risk population. 98% of Pap tests were liquid-based cytology (LBC) specimens screened using computer-assisted screening. Follow-up diagnoses were correlated with cytology and stratified into age groups. Screening sensitivity was assessed by examining Pap results during 1 year preceding neoplastic diagnoses. Verification bias was adjusted with findings in over 2000 patients with hysterectomies. RESULTS: Of 247,131 Pap tests, 1021 (0.41%) reported AGC results and 662 cases had tissue follow-up. Precancerous or malignant neoplastic histologic outcomes were documented in 101 patients (15.3%), including 8.3% cervical, 6.3% endometrial, and 0.6% ovarian. AGC results were most often associated with neoplastic cervical outcomes in women younger than 40 and with neoplastic endometrial outcomes in women 50 or older. AGC-NOS with a squamous cell abnormality and AGC-EC results suggested cervical neoplasia, while AGC-EM results suggested endometrial neoplasia. CONCLUSIONS: AGC Pap results detected significant numbers of cervical and non-cervical neoplasias. Since 38 of 44 (86%) of AGC-detected carcinomas were endometrial or ovarian, HPV co-testing would not have aided screening in detecting the majority of malignancies diagnosed after AGC Pap results. Verification bias-adjusted Pap screening sensitivity in the laboratory for detection of significant neoplastic cervical disease was 93%.

宫颈涂片发现不典型腺细胞的662例病人的组织学随访：结果来源于应用敏感筛查方法的一大型妇产教学医院

目的：宫颈涂片中发现的不典型腺细胞(AGC)的解释及其对腺体肿瘤的筛查作用是目前存在的难点，因此我们对大量的AGC病例进行了组织学随访并对实验室筛查结果的灵敏性进行了误差校对（verification bias-adjusted ？）。

方法：将宫颈涂片中的AGC-EC(不典型腺细胞-来源于宫颈)，AGC-EM(不典型腺细胞-来源于子宫内膜)，AGC-NOS(不典型腺细胞-来源不明确)列入统计范围，数据来源于主要服务对象是老年低危人群的一医疗中心。98%的宫颈涂片使用的是液基细胞学计算机辅助筛查系统，根据细胞学结果又将随访诊断结果和年龄进行了分组。根据一年后组织学诊断结果对筛查的灵敏性进行了评估，根据超过2000例子宫切除病人的结果进了误差校对（Verification bias was adjusted with findings in over 2000 patients with hysterectomies？）

结果：在247,131例宫颈涂片中，1021 (0.41%)例报告了AGC，对其中的662例进行了组织学随访，发现癌前病变和恶性肿瘤病人101(15.3%)例，其中宫颈占 8.3%,子宫内膜占 6.3% ,卵巢占0.6%. 年龄小于40岁者发现的AGC多与宫颈肿瘤相关，年龄大于等于50岁者发现的AGC多与子宫内膜肿瘤相关，AGC-NOS伴有磷状上皮异常或AGC-EC多提示宫颈肿瘤，而AGC-EM多提示子宫内膜肿瘤。

结论：宫颈涂片发现AGC的病人中有相当部份病人有宫颈或非宫颈的肿瘤。在非典型腺细胞中随访中确认为癌的44例病人中38例(86%)属于子宫内膜癌或卵巢癌，因此宫颈涂片发现AGC随后的HPV基因检测对于发现大多数的恶性肿瘤来说并无帮助。该实验室对宫颈肿瘤检测经过误差校对后的灵敏性是93%。（Verification bias-adjusted Pap screening sensitivity in the laboratory for detection of significant neoplastic cervical disease was 93%.）

(laurelshihxbl 翻译，注：红色部份翻译是否确切，请赵老师和诸位指点，主要是对verification bias-adjusted的中文不太熟悉)

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3 楼发表于2009-06-12 22:06:00举报|引用
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Table 2.

Correlation of the subcategories of 662 AGC cases with precancerous or cancerous lesions in tissue biopsies

Cytologic Dx

AGC/ASC-US

(n=102)

AGC/ASC-H

(n=41)

AGC/HSIL

(n=28)

AGC-EM

(n=99)

AGC-EC

(n=131)

AGC-NOS

(n=261)

Total

(n=662)

CIN2+

3*

(2.9%)

3*

(7.3%)

18**

(64.3%)

0

9*

(6.9%)

9

(3.5%)

42***

(6.3%)

AIS+

1*

(1.0%)

3*

(7.3%)

5**

(17.9%)

0

8*

(6.1%)

4

(1.5%)

21***

(3.2%)

ACH+

3

(2.9%)

0

1

(3.6%)

22

(22.2%)

1

(0.8%)

15

(5.7%)

42

(6.3%)

Metastatic

1

(1.0%)

0

1

(1.0%)

1

(0.8%)

1

(0.4%)

4

(0.6%)

Total

7

(6.9%)

5

(12.2%)

19

(67.9%)

23

(23.2%)

18

(13.7%)

29

(11.1%)

101

(15.3%)

* 1 patient has both AIS and CIN2,3.

**5 patients have both AIS and CIN2,3.

*** in total 8 patients have both AIS and CIN2,3.

Abbreviation: CIN2+, cervical intraepithelial neoplasia 2 above squamous lesions; AIS+, endocervical adenocarcinoma and invasive carcinoma; CAH+, complex atypical hyperplasia above endometrial lesions.

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4 楼发表于2009-06-12 22:07:00举报|引用
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Table 3

The Relation of Age and Subsequent Preneoplastic or Neoplastic lesions in tissue biopsies in Women with AGC Paps

Histopathology

Result ▼

Age<40 years

N=201

≥40 to <50 years

N=248

≥50

N=213

Total

N=662

CIN 2/3 and invasive

Squamous carcinoma

31*

(15.4%)

7**

(2.8%)

4

(1.9%)

42***

(6.3%)

Adenocarcinoma

In situ

8*

(4.0%)

8**

(3.2%)

0

(0%)

16***

(2.4%)

Invasive Cervical Adenocarcinoma

2

(1.0%)

1

(0.4%)

2

(0.9%)

5#

(0.8%)

Atypical Endometrial

Hyperplasia

0

(0%)

3

(1.2%)

5

(2.3%)

8

(1.2%)

Endometrial carcinoma

2

(1.0%)

5

(2.0%)

27

(12.7%)

34

(5.1%)

Ovarian

carcinoma

0

(0%)

1

(0.4%)

3

(1.4%)

4

(0.6%)

Total

38

(18.9%)

22

(8.9%)

41

(19.2%)

101

(15.3%)

* 5 cases with both AIS and CIN 2/3

** 3 cases with both AIS and CIN 2/3

*** Total 8 cases have both AIS and CIN2/3.

# 4 cases of adenocarcinoma, 1 case of adenosquamous carcinoma.

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5 楼发表于2009-06-12 22:11:00举报|引用
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本帖最后由于 2009-06-14 13:34:00 编辑 J Low Genit Tract Dis. 2009 Apr;13(2):79-84.

High-risk human papillomavirus DNA test results are useful for disease risk stratification in women with unsatisfactory liquid-based cytology pap test results.

Zhao C, Austin RM.

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

OBJECTIVES: This study assesses whether high-risk human papillomavirus (HPV) DNA test results from residual vial fluid of unsatisfactory liquid-based cytology(LBC) samples might provide useful information on disease risk. MATERIALS AND METHODS: Patients with unsatisfactory imaged ThinPrep Pap test results and available Hybrid Capture 2 high-risk HPV results were identified at an academic women's hospital laboratory between July 1, 2005, and July 31, 2007. Follow-up repeat cytology results, HPV results, and available biopsy results were analyzed. RESULTS: Three hundred four patients with unsatisfactory cytology results and HPV test results were studied. Eleven (3.6%) of 304 tested positive for HPV DNA, and 293 tested HPV negative. Five (45%) of 11 HPV-positive patients had detectible low-grade squamous intraepithelial/cervical intraepithelial neoplasia 1 during a mean follow-up period of almost 6 months. Among 293 women with negative HPV results, only 1 case of cervical intraepithelial neoplasia 1 was identified during roughly the same follow-up period. CONCLUSIONS: A positive high-risk HPV result associated with an unsatisfactory ThinPrep Pap test result identified patients at risk for diagnosis of an undetected squamous intraepithelial/cervical intraepithelial neoplasia. Negative high-risk HPV results associated with an unsatisfactory LBC had high negative predictive value in this limited study. The overall low detection rate for significant disease on follow-up of all patients with unsatisfactory imaged LBC is similar to findings reported in another LBC study but differs from studies reporting increased risk for undetected disease in women screened with unsatisfactory conventional Pap smears.

对于宫颈液基细胞学检测不满意的病人进行高危HPV-DNA检测是非常有用的宫颈疾病风险评估指标

目的：本文对宫颈液基细胞学检测不满意病人的剩余标本进行了高危HPV-DNA检测，评估高危HPV-DNA检查结果能否对宫颈疾病检查提供有用信息。

方法：将某妇科教学医院2005年1月1日至2007年1月30日的宫颈液基细胞学检测不满意的标本和相应的HC-II高危HPV基因检测结果进行分析，后续随访包括细胞学重复检测，HPV检测及宫颈活检。

结果：细胞学筛查不满意和同时进行了HPV基因检测的共304例病人，其中11例（11/304，3.6%） HPV基因检测阳性，293例基因检测阴性。11例阳性病人中5例（45%）在后续的平均时间为6个月的随访中检测到低级别宫颈上皮内瘤变（CIN-I）。在293例基因检测阴性妇女中，在相同时间的后续随访中，只有1例检测到低级别宫颈上皮内瘤变（CIN-I）。

结论：在本研究有限的病例中发现，宫颈细胞学筛查不满意伴高危HPV基因检测阳性妇女发生未检测到宫颈上皮内瘤变的机率较高，宫颈细胞学筛查不满意伴高危HPV基因检测阴性妇女发生未检测到宫颈上皮内瘤变的机率较低。总体上看，宫颈细胞学筛查不满意后续随访检测到的宫颈病变率较低，该结果与另外的某项液基细胞学（LBC）研究结果相似，但是与其它的研究结果不同，即传统宫颈细胞学涂片不满意时未检测到的宫颈病变发生率增加。

(laurelshihxbl翻译)

J Low Genit Tract Dis. 2009 Apr;13(2):79-84.

High-risk human papillomavirus DNA test results are useful for disease risk stratification in women with unsatisfactory liquid-based cytology pap test results.

Zhao C, Austin RM.

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

OBJECTIVES: This study assesses whether high-risk human papillomavirus (HPV) DNA test results from residual vial fluid of unsatisfactory liquid-based cytology(LBC) samples might provide useful information on disease risk. MATERIALS AND METHODS: Patients with unsatisfactory imaged ThinPrep Pap test results and available Hybrid Capture 2 high-risk HPV results were identified at an academic women's hospital laboratory between July 1, 2005, and July 31, 2007. Follow-up repeat cytology results, HPV results, and available biopsy results were analyzed. RESULTS: Three hundred four patients with unsatisfactory cytology results and HPV test results were studied. Eleven (3.6%) of 304 tested positive for HPV DNA, and 293 tested HPV negative. Five (45%) of 11 HPV-positive patients had detectible low-grade squamous intraepithelial/cervical intraepithelial neoplasia 1 during a mean follow-up period of almost 6 months. Among 293 women with negative HPV results, only 1 case of cervical intraepithelial neoplasia 1 was identified during roughly the same follow-up period. CONCLUSIONS: A positive high-risk HPV result associated with an unsatisfactory ThinPrep Pap test result identified patients at risk for diagnosis of an undetected squamous intraepithelial/cervical intraepithelial neoplasia. Negative high-risk HPV results associated with an unsatisfactory LBC had high negative predictive value in this limited study. The overall low detection rate for significant disease on follow-up of all patients with unsatisfactory imaged LBC is similar to findings reported in another LBC study but differs from studies reporting increased risk for undetected disease in women screened with unsatisfactory conventional Pap smears.

对于宫颈液基细胞学检测不满意的病人进行高危HPV-DNA检测是非常有用的宫颈疾病风险评估指标

目的：本文对宫颈液基细胞学检测不满意病人的剩余标本进行了高危HPV-DNA检测，评估高危HPV-DNA检查结果能否对宫颈疾病检查提供有用信息。

方法：将某妇科教学医院2005年1月1日至2007年1月30日的宫颈液基细胞学检测不满意的标本和相应的HC-II高危HPV基因检测结果进行分析，后续随访包括细胞学重复检测，HPV检测及宫颈活检。

结果：细胞学筛查不满意和同时进行了HPV基因检测的共304例病人，其中11例（11/304，3.6%） HPV基因检测阳性，293例基因检测阴性。11例阳性病人中5例（45%）在后续的平均时间为6个月的随访中检测到低级别宫颈上皮内瘤变（CIN-I）。在293例基因检测阴性妇女中，在相同时间的后续随访中，只有1例检测到低级别宫颈上皮内瘤变（CIN-I）。

结论：在本研究有限的病例中发现，宫颈细胞学筛查不满意伴高危HPV基因检测阳性妇女发生未检测到宫颈上皮内瘤变的机率较高，宫颈细胞学筛查不满意伴高危HPV基因检测阴性妇女发生未检测到宫颈上皮内瘤变的机率较低。总体上看，宫颈细胞学筛查不满意后续随访检测到的宫颈病变率较低，该结果与另外的某项液基细胞学（LBC）研究结果相似，但是与其它的研究结果不同，即传统宫颈细胞学涂片不满意时未检测到的宫颈病变发生率增加。

(laurelshihxbl翻译)

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6 楼发表于2009-06-12 22:13:00举报|引用
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Table 1. Reasons for Unsatisfactory Classification

Reasons*

HR HPV-

n=293 (96.4%)

HR HPV+

n=11 (3.6%)

Total

N=304

Inadequate squamous component

269

(91.8%)

7

(63.6%)

276

(90.8%)

Blood

31

(10.6%)

0

31

(10.2%)

inflammation

26

(8.9%)

1

(9.1%)

27

(8.9%)

Thick preparation

5

(1.7%)

2

(1.8%)

7

(2.3%)

Bacteria

3

(1.0%)

1

(9.1%)

4

(1.3%)

Cytolysis

2

(0.7%)

1

(9.1%)

3

(1.0%)

Two factors*

43

(14.7%)

1

(9.1%)

44

(14.5%)

*The lists include cases with two factors.

HR HPV, high risk human papillomavirus.

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7 楼发表于2009-06-12 22:14:00举报|引用
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Table 2. Follow-up Pap Test and Biopsy Results for Unsatisfactory Cases

Initial Cytologic diagnosis Cervical biopsy

hrHPV test ASC-US LSIL Negative Unsatisfactory CIN 1*

Positive (n=11) 1 (9.1%) 4 (36.4%) 6 (54.5%) 0 5 (45.5%)

Negative (n=205) 6 (2.9%) 193 (94.2%) 6 (2.9%) 1 (0.5%)

Total (n=216) 7 (3.2%) 4 (1.9%) 199 (92.1%) 6 (2.8%) 6 (2.8%)

*In initial hrHPV positive group, all four cases with LSIL and one with ASC-US in the repeated Pap tests had CIN 1 confirmed by colposcopic cervical biopsy in histologic follow-up; In initial hrHPV negative group, one of ASC-US cases was diagnosed as CIN 1 in histologic follow-up and hrHPV positive.

hrHPV, high risk human papillomavirus; ASC-US, atypical squamous cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesion; CIN, cervical intraepithelial neoplasia.

Table 3. Follow-up hrHPV DNA Test Results for Unsatisfactory Cases

Initial

hrHPV test Repeated case No Repeated hrHPV positive P value

Positive 6 3 (50%)

Negative 99 4 (4.0%) 0.0034

Total 105 7 (6.7%)

hrHPV, high risk human papillomavirus.

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8 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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9 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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10 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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11 楼发表于2009-06-12 22:22:00举报|引用
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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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12 楼发表于2009-06-12 22:24:00举报|引用
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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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13 楼发表于2009-06-12 22:26:00举报|引用
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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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14 楼发表于2009-06-12 22:27:00举报|引用
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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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15 楼发表于2009-06-12 22:29:00举报|引用
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先置顶，免得沉了。

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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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17 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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18 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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19 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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20 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

0

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