The Risk of False-Positive Histology According to the Reason for Colposcopy Referral in Cervical Cancer Screening

Abstract

All cervical intraepithelial neoplasia (CIN) diagnoses identified during the New Technologies for Cervical Cancer trial (ISRCTN81678807) were blindly reviewed by 2 pathologists. Original diagnoses based on colposcopy-guided biopsies were compared with those made by the reviewers who had access to all clinical histologic samples (including postsurgical). Cases downgraded from CIN 2+ by the reviewers were considered indicative of unnecessary treatments. The analyses are presented according to the molecular (high-risk human papillomavirus [HPV]) and/or cytologic diagnosis used to refer the women for colposcopy. We reviewed 812 CIN 1 and 364 CIN 2 + diagnoses. The specificity of colposcopy-guided biopsy was 98% and the sensitivity, 84%. The probability of unnecessary treatment was 27% for women with atypical squamous cells of undetermined significance cytologic findings and 8% for women with low-grade squamous intraepithelial lesion or worse, 10% for HPV+ and positive cytologic findings, and 16% for HPV+ alone. The positive predictive value of the first-level screening test was inversely associated with probability of a histologic false-positive result (P = .015). In screening, a low positive predictive value of the colposcopy-referring test may result in unnecessary treatments.

Clinical Impact of the Analytical Specificity of the Hybrid Capture 2 Test: Data from the New Technologies for Cervical Cancer (NTCC) Study

“…Overall, the loss in clinical sensitivity that resulted by missing the HPV types not targeted by HC2 would be small, in line with previous reports (15) suggesting that efforts to increase the number of targeted HPV types (i.e., HPV-53, HPV-66, and others) in HPV screening tests would not significantly improve clinical sensitivity. In addition, the probability of progression of these CINs is unknown, and histological false positives cannot be excluded (31,33). Conversely, improvements in analytical specificity would have a nonnegligible impact in reducing unneeded triage and/or colposcopy.…”

“…All colposcopically suspected areas were biopsied. Biopsy samples of women with a CIN diagnosis were reviewed blindly to test results (31).…”

Human papilloma virus genotyping for the cross‐sectional and longitudinal probability of developing cervical intraepithelial neoplasia grade 2 or more

“…The same exercise was repeated at the time of the second screening round. The results of such reviews were previously reported 14, 16, 17, 22, 23. Adenocarcinoma in situ was considered with CIN3.…”

Raman spectroscopy for screening and diagnosis of cervical cancer

“…However, the grading characteristics can be quite subjective and pre-malignancy may not be visually perceptible at all. The sensitivity and specificity of colposcopy guided biopsy has been shown to be 75-90% and 97-99% respectively [12], but the subjective interpretation of histologic classification is the main issue leading to poor inter-observer agreement [13 -15].…”