Reproducibility of cervical intraepithelial neoplasia diagnosis on histological review of cervical punch biopsies from a visual inspection with acetic acid and HPV detection-based screening program.

OBJECTIVE: To assess the reproducibility of cervical intraepithelial neoplasia (CIN) diagnosis in a visual inspection with acetic acid (VIA) and HPV detection-based screening program, and to correlate CIN diagnosis with oncogenic HPV status. METHODS: A total of 9630 women were screened by VIA and high-risk HPV detection at community outreach clinics in India between June 2011 and June 2012. Biopsies obtained from women who were positive on either test were reviewed by two pathologists blinded to the histological diagnoses originally made by pathologists working at the Chittaranjan National Cancer Institute. RESULTS: The interobserver agreement between the pathologists' diagnoses and the diagnoses made by the expert reviewers on 424 slides was fair (kappa = 0.26). There was a distinct difference in agreement in detecting CIN 2 (kappa = 0.21) and detecting CIN 3 (kappa = 0.74). The overall agreement in diagnosis improved when the slides obtained from the HPV-positive women were considered (kappa = 0.5). Almost half of the discordant CIN 2 cases were high-risk HPV negative. CONCLUSION: Diagnosis of CIN 2 is poorly reproducible. The natural history of CIN 2 lesions is more similar to CIN 1 than CIN 3; it is therefore necessary to re-evaluate whether to consider CIN 2 lesions as high-grade squamous intraepithelial lesions with CIN 3, as in the Bethesda system of classification.

Interobserver agreement in the reporting of cervical biopsy specimens obtained from women screened by visual inspection with acetic acid and hybrid capture 2.

Visual inspection with acetic acid (VIA) and human papillomavirus detection have sensitivity higher than cytology but lower specificity. The high false-positive rate of either test poses a challenge to the colposcopists who obtain biopsies from the innocuous changes and to the pathologists who have to interpret large numbers of specimens that are either normal or have low-grade abnormalities. Interobserver variation in histopathologic interpretations of cervical punch biopsy specimens is high, specially for the lower-grade abnormalities. Use of the modified Bethesda system to report histology in place of the cervical intraepithelial neoplasia (CIN) system has the potential to reduce such variability as there are fewer categories. The present study aimed to assess the interobserver agreement to interpret cervical punch biopsies when both pathologists followed the modified Bethesda classification system and also when one pathologist followed the modified Bethesda classification system and the other followed the CIN classification system. Colposcopy-directed punch biopsies were obtained from VIA and/or Hybrid Capture 2-positive women. The Institute pathologist interpreted the slides using the CIN system. Blinded review was done by 2 external pathologists who independently interpreted cervical punch biopsies using the Bethesda system. The Institute pathologist's diagnoses based on CIN system were converted post hoc into categories belonging to the Bethesda system for comparison. The overall agreement was poor (κ=0.36). The lowest agreement was observed in the low-grade squamous intraepithelial lesion category (κ=0.23) and the highest in the squamous cell carcinoma category (κ=0.76). The agreement between the reviewers, both of whom used the Bethesda system, was substantial.

Prevalence of high-risk human papillomavirus and cervical intraepithelial neoplasias in a previously unscreened population--a pooled analysis from three studies.

Population prevalence of human papillomavirus (HPV) and cervical intraepithelial neoplasias (CIN) is an important indicator to judge the disease burden in the community, to monitor the performance of cervical cancer screening program and to assess the impact of HPV vaccination program. India being a country without any cervical cancer screening program has no published data on the population prevalence of CIN and only a few large community-based studies to report the high-risk HPV prevalence. The objective of our study was to study HPV and CIN prevalence in a previously unscreened population. We pooled together the results of three research studies originally designed to assess the performance of visual inspection after acetic acid application and Hybrid Capture 2 (HC 2). Nearly 60% of the screened women had colposcopy irrespective of their screening test results. The diagnosis and grading of cervical neoplasias were based on histology. The age standardized prevalence of HPV by HC 2 test was 6.0%. Age-adjusted prevalence of CIN1 and CIN2 was 2.3% and 0.5%, respectively. The age-adjusted prevalence of CIN3 was 0.4% and that of invasive cancer was 0.2%. The prevalence of high-risk HPV was relatively low in the population we studied, which is reflected in the low prevalence of high-grade CIN. The prevalence of CIN3 remained constant across age groups due to absence of screening.