Reflex Human Papillomavirus Test Results as an Option for the Management of Korean Women With Atypical Squamous Cells Cannot Exclude High‐Grade Squamous Intraepithelial Lesion

Background.

Current guidelines recommend initial colposcopy with biopsy regardless of human papillomavirus (HPV) test results in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). The purpose of this study was to evaluate the value of HPV testing in women with ASC-H based on colposcopic pathology results.

Materials and Methods.

A multicenter cross-sectional study was carried out at three academic hospitals and involved 40,847 Korean women who underwent cervical cancer screening with cytology and HPV tests with or without subsequent colposcopic biopsies between January 2007 and December 2013.

Results.

ASC-H was diagnosed in 276 women (0.7%). Only 6 of 68 (8.8%) women with ASC-H who were HPV negative had cervical intraepithelial neoplasia grade ≥2 (CIN ≥2) lesions, whereas 47.4% of the women with ASC-H who were HPV positive had CIN ≥2 lesions. No cases of invasive cervical cancer were diagnosed among women with ASC-H who were HPV negative. Logistic regression analysis was performed using the group with normal Papanicolaou test results and HPV-negative status as the reference group. Women with ASC-H who were HPV positive had a significantly increased risk of CIN ≥2 lesions, whereas no significant increase was observed in patients with ASC-H and HPV-negative status.

Conclusion.

If the result of the HPV test was negative, the risk of CIN ≥2 lesions in Korean women with ASC-H cytology was low. Reflex HPV testing should be an option for the management of women with cytology showing ASC-H to decrease unnecessary colposcopic biopsies, which are expensive and invasive.

Implications for Practice:

Current American Society for Colposcopy and Cervical Pathology guidelines recommend universal colposcopy for the management of women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on cytology, regardless of human papillomavirus (HPV) test results. The present study suggested that HPV cotesting in patients with ASC-H cytology can provide more detailed and useful information regarding the risk of high-grade cervical intraepithelial neoplasia (CIN) lesions and the need for further treatment. When the result of the HPV test was negative, the risk of CIN lesions of grade ≥2 in women with ASC-H cytology was low. Consequently, reflex HPV testing, rather than immediately performance of invasive and expensive colposcopy with biopsy, should be an option for the management of women with ASC-H.     

Clinical significance of the diagnosis of low‐grade squamous intraepithelial lesion,cannot exclude high‐grade squamous intraepithelial lesion

BACKGROUND:

The diagnosis of low‐grade squamous intraepithelial lesion (LSIL), cannot exclude high‐grade squamous intraepithelial lesion (LSIL‐H) was not included in the 2001 Bethesda System. It is used in some institutions to diagnose cases that fulfill criteria for both the diagnosis of LSIL and atypical squamous cells, cannot exclude high‐grade squamous intraepithelial lesion (ASC‐H). In this study, the authors reviewed their experience with cases reported as LSIL‐H during a 4‐year interval.

METHODS:

Clinical information and histologic follow‐up data were retrieved for Papanicolaou (Pap) tests (PTs) that were diagnosed as LSIL‐H, LSIL, ASC‐H and high‐grade squamous intraepithelial lesion (HSIL) from January 1, 2004 to December 31, 2007.

RESULTS:

Of 235,645 PTs (97% SurePath) that were processed during the study period, the laboratory diagnosed 0.52% as ASC‐H, 2% as LSIL, 0.30% as LSIL‐H, and 0.39% as HSIL. Biopsy follow‐up was available for 47%, 49%, 56.7% and 74% of these cases, respectively. Cervical intraepithelial neoplasia 2 (CIN‐2) and CIN‐3 or more severe lesions (CIN‐3+) were identified on follow‐up cervical biopsy more often in women who had diagnoses of LSIL‐H and ASC‐H (33.14% and 26.33%, respectively) than in women who had a diagnosis of LSIL (16.11%).

CONCLUSIONS:

The similarity of histologic follow‐up results between LSIL‐H and ASC‐H suggested that the management of women who have a diagnosis of LSIL‐H should be similar to the management of women who have a diagnosis of ASC‐H. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Pathology correlates of a Papanicolaou diagnosis of low‐grade squamous intraepithelial lesion,cannot exclude high‐grade squamous intraepithelial lesion

BACKGROUND.

The objective of this study was to compare findings after a cytologic report of low‐grade squamous intraepithelial lesion, cannot exclude high‐grade squamous intraepithelial lesion (LSIL‐H) with findings after a report of low‐grade squamous intraepithelial lesion (LSIL).

METHODS.

A review of patient records revealed that 312 women had cytologic findings of LSIL‐H, and 324 consecutive women in a comparison group had cytologic findings of LSIL during 2005. Findings over 6 months after diagnosis were retrieved and analyzed using chi‐square tests, Fisher exact tests, and independent group t tests.

RESULTS.

Histology was available for 194 of 312 women (64%) with LSIL‐H and for 184 of 324 women (57%) with LSIL. Of these, 47 of 194 women (24%) with LSIL‐H had grade 2 cervical intraepithelial neoplasia or greater (CIN2+) versus 13 of 184 women (7%) with LSIL (P < .0001). No cancers were identified. High‐grade SIL cytology was reported in 2 of 105 women who had LSIL (2%) and in 4 of 93 women who had LSIL‐H (4%). Women with LSIL‐H who were positive for CIN2+ were younger than those without CIN2+ (25 years vs 30 years; P = .0067)

CONCLUSIONS.

Clinicians whose laboratories report LSIL‐H should manage women who have LSIL‐H with colposcopy, whereas only serial cytologic surveillance is required after a report of LSIL. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

Performance of a low cost magnifying device,magnivisualizer, versus colposcope for detection of pre-cancer and cancerous lesions of uterine cervix

Objective

To assess the performance of a low cost magnifying device (Magnivisualizer) compared to a standard optical colposcope for detection of precancerous and cancerous lesions of the uterine cervix.

Methods

A total of 659 consecutive symptomatic women attending a gynecologic outpatient clinic underwent unaided visual inspection followed by cytology, visual inspection of the cervix using 5% acetic acid (VIA), and VIA under magnification (VIAM) with the Magnivisualizer. All women, independently of test results, were referred for colposcopic examination. Colposcopic-directed biopsies were obtained from all positive lesions and compared to positive VIAM cases.

Results

The detection rate for VIA positive lesions was 12% (134/659), while it was 29% for VIAM positive lesions (191/659). The sensitivities of detection of cervical intraepithelial neoplasia (CIN) 2 and higher lesions were 61.7% for VIA, 88.3% for VIAM, and 86.7% for colposcopy, with a specificity of 58.5% for VIA, 55.8% for VIAM, and 90.4% for colposcopy. The performance of colposcopy and VIAM was moderate (κ, 0.48; 95% confidence interval [CI], 0.41 to 0.54) for detection of CIN 1 and higher lesions and excellent (κ, 0.87; 95% CI, 0.82 to 0.94) for detection of CIN 2 and higher lesions.

Conclusion

In low resource settings, where colposcopic facilities are not available at the community level, a simple low-cost, handheld Magnivisualizer can be considered a valid option for detection of cervical precancerous and cancerous lesions. However, it cannot replace traditional colposcopy because it has a low specificity that results in many unnecessary biopsies.     

p16INK4a is superior to high‐risk human papillomavirus testing in cervical cytology for the prediction of underlying high‐grade dysplasia

BACKGROUND

The primary goal of this study was to compare the clinical performance of an optimized and rigorously controlled immunocytochemical (ICC) assay for p16^INK4a to high‐risk (HR) human papillomavirus (HPV) detection by polymerase chain reaction (PCR) as diagnostic adjuncts for cytology specimens from colposcopy patients.

METHODS:

The study included 403 cervical cytology specimens collected within 3 months of colposcopy. The colposcopic impression and cervical biopsy diagnosis served as the standards for correlation with cytological, p16^INK4a, and HPV data. p16^INK4a was evaluated using an immunoperoxidase‐based assay that was linear over 4 logs for the detection of HeLa‐spiked positive control cytology specimens, using a threshold for positive test results that was based on receiver operating characteristic curve analysis. HR‐HPV was detected by multiplex PCR using genotype‐specific primers.

RESULTS:

In all combined diagnostic categories (negative for intraepithelial lesion and malignancy, atypical glandular cells, atypical squamous cells of undetermined significance, atypical squamous cells cannot exclude high‐grade squamous intraepithelial lesion, low‐grade squamous intraepithelial lesion, and high‐grade squamous intraepithelial lesion), the p16^INK4a ICC and HR‐HPV assays, respectively, had sensitivity of 81.7% and 83.3% (P = .81) and specificity of 78.1% and 50.9% (P < .001) for the detection of underlying ≥grade 2 cervical intraepithelial neoplasia (CIN) lesions on biopsy. Furthermore, the positive predictive value of p16^INK4a ICC was greater than that of HR‐HPV for patients with biopsies ≥CIN‐2 (41.2% and 24.2%, respectively, P = .001).

CONCLUSIONS:

This p16^INK4a immunocytochemical assay has superior specificity but similar sensitivity to HR‐HPV testing to predict underlying high‐grade dysplastic lesions in patients who are referred for colposcopy. The determination of the overall performance characteristics of p16^INK4a immunocytochemistry, as an independent test or in combination with HPV testing in low‐risk screening populations, however, will require subsequent large‐scale prospective clinical trials. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

The clinical performance of APTIMA human papillomavirus and Hybrid Capture 2 assays in the triage of lesser abnormal cervical cytologies

Objective

This study was performed to evaluate the clinical performance of APTIMA human papillomavirus (AHPV) assay and Hybrid Capture 2 (HC2) assay in screening for cervical disease, especially in women with atypical squamous cell of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL).

Methods

A total of 411 women diagnosed with ASC-US or LSIL were referred and further triaged by HC2 test. Prior to colposcopy, liquid-based cytology specimens were collected for the AHPV assay. Sensitivity and specificity were established based on the histological findings of cervical intraepithelial neoplasia (CIN).

Results

In all 411 subjects, the positive detection rate of AHPV assay was 70.8% (95% confidence interval [CI], 66.4 to 75.2), which was significantly lower than the positive detection rate of 94.9% obtained using HC2 test (95% CI, 92.3 to 96.8). Only one CIN 3-positive case was detected among the 120 AHPV-negative women, which was then confirmed by Pap smear test to be LSIL. The sensitivities of AHPV and HC2 for CIN 3 were similar (94.1% and 100%, respectively). However, AHPV showed a significantly higher specificity than HC2 test (30.2% and 5.3%, respectively; p<0.001).

Conclusion

AHPV assay is effective in identifying CIN 3-positive cases because of its high specificity and lower false-negative rate. The use of AHPV for the triage of ASC-US and LSIL might help to reduce the referral rate of colposcopy during cervical cancer screening.     

Atypical squamous cells,cannot exclude a high‐grade intraepithelial lesion and its clinical significance in postmenopausal,pregnant, postpartum,and contraceptive‐use patients

BACKGROUND.

Previous studies have confirmed the low predictive value of a diagnosis of atypical squamous cells, cannot exclude a high‐grade squamous intraepithelial lesion (ASC‐H) in a Papanicolaou (Pap) smear for subsequent high‐grade dysplasia in the postmenopausal age group. It appears plausible that the decrease in estrogen inherent in the postmenopausal state likely produces reactive cytologic atypia, which is misinterpreted as ASC‐H. The change in hormone levels observed in pregnant patients, postpartum patients, and contraceptive users, as a corollary, potentially could create a similar diagnostic dilemma. In the current study, the impact of age and altered hormone status on the frequency of ASC‐H was assessed to answer the following questions: Is the low predictive value of ASC‐H in postmenopausal women an age‐related phenomenon, and do other states that result in decreased levels of estrogen relative to progesterone have a similar association?

METHODS.

Pap smears that were diagnosed as ASC‐H were divided into postmenopausal, pregnant, postpartum, and contraceptive‐use categories. Each Pap smear slide was reviewed to assess the degree of atrophy and the character of atypical cells. The frequency of high‐grade follow‐up (histology and/or Digene Hybrid Capture II) in the postmenopausal group was compared with the frequency of high‐grade follow‐up in the pregnant, postpartum, and contraceptive‐use categories using the chi‐square test. The pregnant, postpartum, and contraceptive‐use categories also were compared statistically among each other with the chi‐square test.

RESULTS.

In total, 195 cases met the criteria for study inclusion. The percentage of patients who had subsequent high‐grade follow‐up was 22.5% in the postmenopausal group, 79.6% in the pregnant group, 66.7% in the postpartum group, and 60% in the contraceptive‐use group. When these data were subjected to the chi‐square test, there was a statistically significant difference (P<.0001) between the predictive value of subsequent high‐grade follow‐up in the postmenopausal group compared with the other patient groups. When the chi‐square test was applied to the intercomparison of the pregnant, postpartum, and contraceptive‐use categories, there were no significant differences (P > .05) in high‐grade follow‐up between any of these groups.

CONCLUSIONS.

The diagnosis of ASC‐H in postmenopausal Pap smears has a low predictive value in the subsequent diagnosis of high‐grade squamous lesions in stark contrast to the pregnant, postpartum, and contraceptive‐use categories. This suggests that age rather than hormone alterations affects the capacity of ASC‐H to predict subsequent high‐grade squamous intraepithelial lesions. In addition, there are no definite cytomorphologic criteria that can be used to distinguish reliably between benign cellular changes and possible high‐grade squamous lesions in these Pap smears. Digene Hybrid Capture II testing, although helpful, does not have 100% correlation with subsequent tissue/Pap smear follow‐up and cannot be used alone to triage this group of women for colposcopy. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

Use of high-risk human papillomavirus testing in patients with low-grade squamous intraepithelial lesions

BACKGROUND

The role of testing for high‐risk human papillomavirus (HR HPV) when triaging women with a cytologic diagnosis of low‐grade squamous intraepithelial lesion (LSIL) has not been well established. The objective of the current study was to correlate the status of HR HPV with the incidence of cervical intraepithelial neoplasia 2 and more severe lesions (CIN 2+) on tissue follow‐up in women with LSIL.

METHODS

A total of 1046 women with LSIL and HR HPV testing were identified in the database of a large teaching hospital within a 12‐month period. HR HPV testing was performed using the Hybrid Capture 2 assay with 1 relative light unit/cutoff as the cutoff.

RESULTS

Of the 1046 women with LSIL and concurrent HR HPV testing, 82.3% tested positive for HR HPV, 91.1% of whom were women aged < 30 years and 73% of whom were women aged ≥ 30 years (P < .001). Cytologic and/or histologic follow‐up was available in 979 (93.6%) women; 25.5% had negative follow‐up, 62.5% were found to have CIN 1 lesions, and 12.0% had CIN 2+ lesions. The sensitivity and negative predictive value of HR HPV status as a marker of CIN 2+ lesions were 98.3% and 98.9%, respectively. The colposcopy rate was 73.3% and 96.9% for women aged ≥ 30 years and women aged < 30 years, respectively (P = .01).

CONCLUSIONS

Using 1 RLU/CO as the cutoff value, HR HPV testing was found to be highly sensitive for detecting CIN 2+ lesions in women with LSIL. The colposcopy rate was significantly lower in women aged ≥ 30 years compared with women aged < 30 years. Triaging with HR HPV testing may be indicated in women aged ≥ 30 years with LSIL cytology, but not in women aged < 30 years. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.     

Human papillomavirus testing for triage of women with low‐grade squamous intraepithelial lesions

Low‐grade squamous intraepithelial lesion (LSIL) is a common cytologic finding in cervical screening, yet only about 10–20% have significant histologic abnormalities and these are almost always positive for high‐risk human papillomavirus (hrHPV). This analysis aims to clarify the role of hrHPV DNA testing in the triage of women with LSIL cytology. In the ATHENA screening trial, we examined 1,084 cases of LSIL, of which 925 had an evaluable biopsy, to determine the extent to which hrHPV testing can identify those patients who have precursor lesions in need of immediate clinical referral and those who have changes more likely to regress spontaneously. Overall, 71.2% of LSIL cases were hrHPV positive, but the prevalence was age dependent, with only 56.1% in women ≥40 years. Among women with LSIL, 11.6% (107/925) had a cervical intraepithelial neoplasia grade 2 or worse (CIN2+) histologic diagnosis and, of these, only nine were hrHPV negative. For CIN3+, 91.7% (44/48) of women with LSIL were hrHPV positive. The negative predictive value of hrHPV testing for CIN3+ in LSIL was 100% for women aged ≥40 years. Women who were HPV16 positive had a higher positive predictive value for CIN2+ (25.4%) than those who were positive for 12 other pooled hrHPV types (11.5%). Testing for hrHPV in women with LSIL is effective in identifying high‐grade cervical lesions, thereby avoiding unnecessary referrals to colposcopy and potential over‐treatment of non‐progressive lesions, especially for women aged ≥40 years.     

4 种不同检查方法在宫颈癌筛查中的临床应用价值*

目的:了解4 种不同检查方法在宫颈癌筛查中的临床应用价值。方法:采用第二代杂交捕获技术（hybrid capture 2,HC-II）检测13种高危型人乳头瘤病毒（human papillomavirus ,HPV ）、薄层液基细胞学技术（Liquid-based cytology test,LCT ）检测宫颈脱落细胞、醋酸肉眼检查（visual inspection with acetic acid,VIA）和阴道镜检查4 种方法对2004年11月～2004年12月深圳南山区华侨城区域15～59岁有性生活女性共1 137 例进行盲法同步宫颈癌筛查。对阴道镜检查异常或可疑异常者行阴道镜下直接活检;对HPV 阳性并且LCT ≥未明确诊断意义的不典型鳞状上皮细胞（atypical squamous cells of undetetemined sign,ASCUS ）,或HPV 阴性但LCT ≥低度鳞状上皮内病变（low grade squamous intraepithelial lesion ,LSIL ）的妇女再次行阴道镜下活组织病理学检查,以病理结果作为验证4种检查方法的金标准。结果:共取病理122 例。病理结果证实该人群中无宫颈癌病例:子宫颈上皮内瘤变（cervical intraepithelial neoplasia ,CIN）Ⅲ级3 例,CIN Ⅱ级11例,CIN Ⅰ级36例;慢性宫颈炎和鳞状上皮化生69例;正常宫颈3 例。人群的高危HPV 总检出率为14.0% ;LCT 阳性率为12.6% ;VIA 阳性率为12.5% ;阴道镜阳性率为13.6% 。随宫颈病变级别升高,高危HPV 感染率及LCT 阳性率均呈趋势性增加（P<0.005）;VIA 和阴道镜阳性率在各级宫颈病变中无统计学差异,但在宫颈病变组阳性检出率明显高于正常宫颈组。高危HPV 对宫颈高度病变的敏感性、特异性、准确性、阳性预测值、阴性预测值、阳性似然比和阴性似然比分别为100% 、87.1% 、87.3% 、8.8% 、100% 、7.6% 和0;LCT 以上各指标分别为92.9% 、88.4% 、88.5% 、9.1% 、99.9% 、8.0% 和8.0% ;VIA 以上各指标分别为35.7% 、96.0% 、95.3% 、10.0% 、99.2% 、8.9% 和67.0% ;阴道镜以上各指标分别为50.0% 、86.8% 、86.4% 、4.5% 、99.3% 、3.8% 和58.0% 。结论:高危HPV 检测和LCT 检查均为目前宫颈癌筛查较好的方法,VIA 和阴道镜检查敏感性较差,漏诊率高,不适合大范围筛查,但二者阴性预测值均较高,可应用于临床病例诊断。      

Treatment of the patients with abnormal cervical cytology: a "see-and-treat" versus three-step strategy

Objective

To examine the correlation between cervical cytology and final histological results in patients who have undergone loop electrosurgical excision procedure (LEEP) with or without colposcopy-directed biopsy.

Methods

A retrospective review was performed of 829 patients who underwent LEEP for abnormal cervical cytology at Gangnam Severance Hospital between January 2004 and December 2008. Patients were classified to three groups according to cervical cytology and also divided into two groups based on the treatment they received: see-and-treat group and the standard three-step group. Final histological results were compared for the each study group.

Results

There were no differences in the final histological results between see-and-treat and three-step group in patients with high-grade squamous intraepithelial lesions (HSIL) cytology (N=523) (p=0.71). However, in patients with low-grade squamous intraepithelial lesions (LSIL)/atypical squamous cells of undetermined significance (ASCUS) (N=257) or normal cytology (N=49), the final histological results were significantly different between see-and-treat and three-step group (p<0.001) and the rate of overtreatment was significantly higher in the see-and-treat group (p<0.001).

Conclusion

A see-and-treat protocol may be a viable alternative only in patients with HSIL cytology if colposcopic impression is suggestive of cervical intraepithelial neoplasia (CIN) 2 or 3 lesions.     

新型国产杂交捕获HPV检测技术在ASC-US人群分流中的应用效果评价

目的 探讨基于杂交捕获原理的DH2检测技术在未明确意义的不典型鳞状细胞(Atypical squamous cells of undetermined significance,ASC-US)人群中的分流应用效果.方法 本研究于2016年10月—2018年10月在河南省新密市招募21～64岁普通女性参加研究.所有女性在...     

Papanicolaou test interpretations of “atypical squamous cells,cannot exclude high‐grade squamous intraepithelial lesion”

BACKGROUND.

Management guidelines for women with Papanicolaou (Pap) test interpretations of ASC‐H (atypical squamous cells, cannot exclude high‐grade squamous intraepithelial lesion) reflect substantial risk, which ranges from 10% to 68%, of a cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in their follow‐up histologic samples. The present study was initiated to determine the number of colposcopic procedures and the time frame that are typically required for a definitive diagnosis of a CIN2+ lesion after a Papanicolaou (Pap) test interpretation of ASC‐H in routine practice.

METHODS.

Clinicopathologic data on consecutive ASC‐H interpretations, 97% of which were on liquid‐based preparations, were reviewed. The number of biopsies (which was used in this context as a surrogate indicator for the number of colposcopic procedures) as well as the average duration required for a follow‐up histologic diagnosis of CIN2+ were determined.

RESULTS.

Of 500 ASC‐H interpretations, 75 were excluded for a variety of reasons and 165 lacked follow‐up in our records. The average age and follow‐up duration for the remaining 260 patients was 35.6 years and 18.5 months, respectively. CIN2+ was diagnosed in 49 (40%) of the 122 patients with at least 1 histologic follow‐up. Of these 49 patients, 72% (35 of 49) were diagnosed on the first follow‐up cervical biopsy, 14% (7 of 49) and 8% (4 of 49) were diagnosed on the second and third follow‐up biopsies, respectively; in only 6% (3 of 49) was a fourth follow‐up biopsy required. Overall, an average of 1.53 biopsies (range, 1–4) was required to attain a definitive diagnosis of CIN2+, and 28% of patients required more than 1 follow‐up biopsy. The average period between the index ASC‐H interpretations and CIN2+ diagnoses was 5.5 months. The average time to CIN2+ diagnoses by the first follow‐up biopsy was 3 months; for diagnoses made on subsequent biopsies, the average additional follow‐up duration was 8 months. Of the eventual CIN2+ diagnoses, 84% were rendered within 12 months of their associated index ASC‐H interpretations.

CONCLUSIONS.

1) A substantial subset—28%—of patients with biopsy‐proven CIN2+ after ASC‐H interpretations required more than 1 colposcopy for a definitive diagnosis of a high‐grade dysplastic lesion. 2) If a CIN2+ lesion is present, the vast majority can be diagnosed in a biopsy performed within 1 year of the ASC‐H interpretation. Cancer (Cancer Cytopathol) 2007. © Published 2007 by the American Cancer Society.     

Single-visit approach of cervical cancer screening: See and Treat in Indonesia

Background:

We performed a cross-sectional study in Indonesia to evaluate the performance of a single-visit approach of cervical cancer screening, using visual inspection with acetic acid (VIA), histology and cryotherapy in low-resource settings.

Methods:

Women having limited access to health-care facilities were screened by trained doctors using VIA. If the test was positive, biopsies were taken and when eligible, women were directly treated with cryotherapy. Follow-up was performed with VIA and cytology after 6 months. When cervical cancer was suspected or diagnosed, women were referred. The positivity rate, positive predictive value (PPV) and approximate specificity of the VIA test were calculated. The detection rate for cervical lesions was given.

Results:

Screening results were completed in 22 040 women, of whom 92.7% had never been screened. Visual inspection with acetic acid was positive in 4.4%. The PPV of VIA to detect CIN I or greater and CIN II or greater was 58.7% and 29.7%, respectively. The approximate specificity was 98.1%, and the detection rate for CIN I or greater was 2.6%.

Conclusion:

The single-visit approach cervical cancer screening performed well, showing See and Treat is a promising way to reduce cervical cancer in Indonesia.     

Accuracy of Visual Inspection with Acetic acid in Detecting High-Grade Cervical Intraepithelial Neoplasia in Pre- and Post-Menopausal Thai Women with Minor Cervical CytologicalAbnormalities

Purpose: To determine the accuracy of visual inspection with acetic acid (VIA) in detecting high-gradecervical intraepithelial neoplasia (CIN) in pre- and post-menopausal women with atypical squamous cells ofundetermined significance (ASC-US) and low grade squamous intraepithelial lesion (LSIL) Papanicolaou (Pap)smears. Materials and Methods: Two hundred women (150 pre-menopausal and 50 post-menopausal) with ASCUSand LSIL cytology who attended the colposcopy clinic, Thammasat University Hospital, between March 2013and August 2014 were included. All women underwent VIA testing and colposcopy by gynecologic oncologists.Diagnostic values of VIA testing including sensitivity, specificity, positive predictive value (PPV) and negativepredictive value (NPV) for detecting high-grade CIN were determined using the histopathology obtained fromcolposcopic-directed biopsy as a gold standard. Results: VIA testing was positive in 54/150 (36%) pre-menopausalwomen and 5/50 (10%) post-menopausal women. Out of 54 pre-menopausal women with positive VIA testing,15 (27.8%) had high-grade CIN and 39 (72.2%) had either CIN 1 or insignificant pathology. Ten (10.4%), 43(44.8%) and 43 (44.8%) out of the remaining 96 pre-menopausal women with negative VIA testing had highgradeCIN, CIN 1 and insignificant pathology, respectively. Out of 5 post-menopausal women with positive VIAtesting, there were 4 (80%) women with high-grade CIN, and 1 (20%) women with insignificant pathology. Outof 45 VIA-negative post-menopausal women, 42 (93.3%) women had CIN 1 and insignificant pathology, and 3(6.7%) had high-grade CIN. Sensitivity, specificity, PPV and NPV of the VIA testing were 59.4%, 76.2%, 32.2%and 90.8%, respectively (60%, 68.8%, 27.8% and 89.6% in pre-menopausal women and 57.1%, 97.7%, 80%and 93.3% in post-menopausal women). Conclusions: VIA testing may be used as a screening tool for detectinghigh-grade CIN in women with minor cervical cytological abnormalities in a low-resource setting in order tolower the rate of colposcopy referral.     

Prevalence of HPV infection and cervical intraepithelial neoplasia and attitudes towards HPV vaccination among Chinese women aged 18�C25 in Jiangsu Province

Objective

Few data are available on the epidemiology of HPV and cervical cancer among Chinese women younger than 25 years old. This study aimed to estimate the HPV infection rate and the prevalence of cervical intraepithelial neoplasia (CIN) in women aged 18-25, as well as their knowledge of and attitudes towards HPV vaccination.

Methods

A population-based cervical cancer screening study was conducted on women aged 18-25 in Jiangsu province in 2008. Participants provided socio-demographic, reproductive and behavioral information and completed a survey about their knowledge of and attitudes towards HPV vaccination. Women then underwent a gynecologic exam to provide two cervical exfoliated cell samples for high risk HPV DNA testing and liquid-based cytology (LBC) as well as visual inspection with acetic acid (VIA). Women testing positive for any test were referred to colposcopy and biopsy. The gold standard for diagnosis of cervical lesions was directed or random biopsies.

Results

Within the sample of 316 women, 3.4% of them were diagnosed with CIN grade 2 or worse lesions and 17.1% were found to be positive for HPV DNA. Among these young women, extra-marital sexual behavior of them (OR=2.0, 95%CI: 1.1-3.8) or their husbands (OR=2.6, 95%: 1.4-4.7) were associated with an increased risk of HPV positivity. Although overall HPV awareness was low, after a brief educational intervention, 98.4% reported they would electively receive HPV vaccination and would also recommend that their daughters be vaccinated. However, most urban and rural women reported their ideal maximum out-of-pocket contribution for HPV vaccination to be less than 500 RMB and 50-100 RMB, respectively.

Conclusion

Our study indicates cervical disease burden is relatively high among sampled Chinese women aged 18-25. Appropriate educational interventions for female adolescents and strategies to subsidize vaccine costs are definitely needed to ensure the effectiveness of vaccination campaigns in China.Key words: Cervical cancer, Cervical intraepithelial neoplasia, Human papillomavirus, Knowledge, Attitude     

HPV immunisation and cervical screening—confirmation of changed performance of cytology as a screening test in immunised women: a retrospective population-based cohort study

Background:

To document the effect of bivalent HPV immunisation on cervical cytology as a screening test and assess the implications of any change, using a retrospective analysis of routinely collected data from the Scottish Cervical Screening Programme (SCSP).

Methods:

Data were extracted from the Scottish Cervical Call Recall System (SCCRS), the Scottish Population Register and the Scottish Index of Multiple Deprivation. A total of 95 876 cytology records with 2226 linked histology records from women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. The performance of cervical cytology as a screening test was evaluated using the key performance indicators used routinely in the English and Scottish Cervical Screening Programmes (NHSCSP and SCSP), and related to vaccination status.

Results:

Significant reductions in positive predictive value (16%) and abnormal predictive value (63%) for CIN2+ and the mean colposcopy score (18%) were observed. A significant increase (38%) in the number of women who had to be referred to colposcopy to detect one case of CIN2+ was shown. The negative predictive value of negative- or low-grade cytology for CIN2+ increased significantly (12%). Sensitivity and specificity, as used by the UK cervical screening programmes, were maintained.

Conclusions:

The lower incidence of disease in vaccinated women alters the key performance indicators of cervical cytology used to monitor the quality of the screening programme. These findings have implications for screening, colposcopy referral criteria, colposcopy practice and histology reporting.     

DNA methylation in human papillomavirus-infected cervical cells is elevated in high-grade squamous intraepithelial lesions and cancer

Objective

DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population.

Methods

A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves.

Results

Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively).

Conclusion

DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies.     

宫颈细胞学诊断低度鳞状上皮内病变不除外高度鳞状上皮内病变的临床意义

目的:对宫颈细胞学诊断为低度鳞状上皮内病变不除外高度鳞状上皮内病变(low-grade squamous intraepithelial lesion,cannot exclude high-grade squamous intraepithelial lesion,LSIL-H)与TBS-2001系统中的LSIL、非典型鳞状细胞不除外高度病变(atypical squamous cells,cannot rule out a high grade lesion,ASC-H)和高度鳞状上皮内病变(high-grade squamous intraepithelial lesion,HSIL)的组织病理学结果进行比较,评估LSIL-H的临床风险。方法:对细胞学诊断异常标本即未明确意义的非典型鳞状上皮细胞(atypical squamous cells of undetermined significance,ASC-US)、LSIL、ASC-H和HSIL,采用盲法重新进行回顾性诊断,分级为ASC-US、LSIL、LSIL-H、ASC-H和HSIL。同时追踪组织病理学诊断结果,并分析高危型人乳头瘤病毒(highrisk-HPV)阳性率。结果:总共49000例被纳入分析。重新诊断后,LSIL-H有88例(88/49000,0.17%)。重新分级诊断前,LSIL-H在各异常分级中所占的比例分别为:ASC-US为19.32%(17/88)、LSIL为43.18%(38/88)、ASC-H为34.09%(30/88)、HSIL为3.41%(3/88)。LSIL-H罹患高度病变CIN2/3的概率要高于LSIL,两者相比差异有统计学意义(P<0.01),但均低于HSIL(P<0.01)。LSIL-H与ASC-H的CIN2/3患病率相当(分别为39.47%和38.46%),差异无统计学意义。结论:LSIL-H组织病理学结果证实,其与高度病变之间的关系与ASC-H相近,建议采用与ASC-H同样的方法对这类患者进行临床管理。     

Should LSIL‐H be a distinct cytology category?

BACKGROUND:

The 2001 Bethesda System for gynecologic cervical cytology reporting classifies squamous intraepithelial lesions into low‐grade (LSIL) and high‐grade (HSIL) lesions. An intermediate term, “low‐grade squamous intraepithelial lesion, cannot exclude high‐grade squamous intraepithelial lesion (LSIL‐H),” has been used in a small percentage of LSIL cases. To the authors' knowledge, little is known regarding the human papillomavirus (HPV) status in patients with LSIL‐H.

METHODS:

A total of 808 SurePath specimens obtained between December 2009 and April 2011 were tested for 40 HPV genotypes using DNA microarray, followed by a confirmatory DNA sequencing assay.

RESULTS:

The infection rate for high‐risk HPV in women with LSIL‐H (92%) was strikingly close to that for women with HSIL (91%), which was higher than that for those with LSIL (74%); atypical squamous cells, cannot rule out high‐grade lesion (ASC‐H) (78%); or LSIL and ASC‐H combined (74%). HPV type 16, the most common carcinogenic HPV genotype, was detected in 36% of women with LSIL‐H, which was significantly higher than that in women with LSIL and ASC‐H combined (13.8%), but less than that in women with HSIL (44.6%). Patients with LSIL‐H and HSIL had similar infection rates for low‐risk/intermediate‐risk HPV genotypes, which were lower than those in LSIL or LSIL and ASC‐H combined.

CONCLUSIONS:

Women found to have LSIL‐H on a Papanicolaou test appear to have a unique HPV distribution pattern that clearly differs from LSIL and is comparable to that for HSIL, suggesting an increased risk of high‐grade lesions over that of women with LSIL. Recognizing LSIL‐H as an independent diagnostic category may help in the early identification of the high‐risk subgroup that may require a management algorithm comparable to that for patients with HSIL. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society.