High-risk human papillomavirus testing versus cytology in predicting post-treatment disease in women treated for high-grade cervical disease: a systematic review and meta-analysis.

OBJECTIVE: Currently, women treated for high-grade cervical intraepithelial neoplasia (CIN 2/3) are followed-up by cytology to monitor them for residual and recurrent (post-treatment) disease. This systematic review and meta-analysis determine the test performance of testing for high-risk types of the human papillomavirus (hrHPV), cytology and co-testing (combined hrHPV testing and cytology) in predicting high-grade post-treatment disease (CIN2+). METHODS: Studies that compared at least two of three post-treatment surveillance methods, and were published between January 2003 and May 2011, were identified through a bibliographic database search (PubMed, Embase.com and Wiley/Cochrane Library). Identification of relevant studies was conducted independently by two reviewers with a multi-step process. The reference standard used to diagnose post-treatment disease was histologically confirmed CIN2+. Sensitivity, specificity, diagnostic odds ratios and relative sensitivity and specificity were calculated for each study. Pooled estimates were calculated using a random effects model if heterogeneity among studies was significant, otherwise by using a fixed effects model. Estimates were reported with 95% confidence intervals (95%CI). RESULTS: Out of 2410 potentially relevant citations, 8 publications, incorporating 1513 treated women, were included. Pooled sensitivities were 0.79 (95%CI 0.72-0.85) for cytology, 0.92 (0.87-0.96) for hrHPV testing, and 0.95 (0.91-0.98) for co-testing. HrHPV testing was more sensitive than cytology to predict post-treatment CIN2+ (relative sensitivity 1.15; 95%CI 1.06-1.25). Pooled specificities were 0.81 (95%CI 0.74-0.86) for cytology, 0.76 (0.67-0.84) for hrHPV testing and 0.67 (0.60-0.74) for co-testing. HrHPV testing and cytology had a similar specificity (relative specificity 0.95, 95%CI 0.88-1.02). CONCLUSIONS: This review indicates that the hrHPV test should be included in post-treatment testing 6months after treatment, because hrHPV testing has a higher sensitivity than cytology in detecting high-grade post-treatment disease and has a similar specificity.

Offering self-sampling for human papillomavirus testing to non-attendees of the cervical screening programme: Characteristics of the responders.

BACKGROUND: Self-sampling for high-risk human papillomavirus (hrHPV) testing is accepted by up to 30% of non-attendees to the regular cervical screening programme. Here, the yield of cervical intraepithelial neoplasia (CIN)2 or worse (≥ CIN2) and CIN3 or worse (≥ CIN3) of 15, 274 HPV self-sampling responders amongst non-attendees were compared to that of 176, 027 women participating in regular screening in the same period and in the same region. We also analysed which subpopulations amongst non-attendees are targeted by HPV self-sampling, and which characteristics relate to hrHPV prevalence and yield of ≥ CIN2/≥ CIN3. METHOD: Data from two consecutive self-sampling studies were pooled. ≥ CIN2/≥ CIN3 yields, screening history, age and ethnic status were retrieved from centralised pathology and screening databases, respectively. A logistic regression model was fitted to analyse method of invitation, ethnicity, age group, and screening history as predictors for response rate, hrHPV presence and ≥ CIN2/≥ CIN3 in non-attendees. For screening history analyses, women < 34 years were excluded since it was the first screening round in their life. FINDINGS: ≥ CIN2/≥ CIN3 yields of HPV self-sampling responders were higher than those of screening participants (≥ CIN2: relative risk (RR) = 1.6, 95% confidence interval = 1.4-1.9; ≥ CIN3: RR = 1.8, 95%CI = 1.5-2.1 with relative risk values increasing with age (test of homogeneity:≥ CIN2: p = 0.04; ≥ CIN3: p=0.03). Native Dutch non-attendees responded better than immigrants (32% versus 22%, p<0.001) and those screened in the previous round revealed a higher response than underscreened (i.e. previous smear taken >7 years ago) or never screened (34% versus 25%, p<0.001) women. Strikingly, amongst under- and never screened women aged ≥ 39 years, never screened women responded better (25% versus 23%, p<0.001). ≥ CIN2 rates were higher amongst responding native Dutch women than immigrants (p<0.01), and higher in under-/never screened women than in women screened in the previous round (p<0.01). INTERPRETATION: Offering hrHPV self-sampling increases the efficacy of the screening programme by targeting a substantial portion of non-attendees of all ethnic groups who have not regularly been screened and are at highest risk of ≥ CIN2.