Clinical performance of primary HPV screening cut-off for colposcopy referrals in HPV-vaccinated cohort: Observational study.

Objective: To understand the effect of changing from cytology-based to primary HPV screening on the positive predictive value (PPV) of colposcopy referrals for cervical intraepithelial neoplasia (CIN) in a cohort offered HPV vaccination.

Design: Retrospective pre/post observational cohort study.

Setting: Scotland.

Population Or Sample: 2193 women referred to colposcopy between September 2019 and February 2020 from cytology-based screening and between September 2020 and February 2021 from primary high-risk HPV (hrHPV) screening.

Methods: Calculating positive predictive values (PPVs) for two cohorts of women; one having liquid-based cytology screening and the other, the subsequent hrHPV cervical screening as a pre/post observational study.

Main Outcome Measures: Positive predictive values of LBC and hrHPV cut-offs for colposcopy referral for CIN at colposcopy.

Results: Three papers fitted our criteria; these reported results only for cytology-based screening. The PPV was lower for women in HPV-vaccinated cohorts indicating a lower prevalence of disease. Vaccination under the age of 17 had the lowest PPV reported. Scottish colposcopy data concerning hrHPV and cytology showed a non-significant difference between PPV (17.5%, 95% CI 14.3-20.7, and 20.6, 95% CI 16.7-24.5, respectively) for referrals with a cut-off of low grade dyskaryosis (LGD); both met the standard set of 8-25%. The hrHPV PPV (66.7, 95% CI 56.8-76.6) was comparable to cytology (64.1, 95% CI 55.8-72.4) for referrals with a cut-off of high grade dyskaryosis (HGD) but neither met the standard set of 77-92%.

Conclusions: Current literature only provides PPVs for LBC and, overall, the vaccinated cohort had lower PPVs. Only LG dyskaryosis met PHE criteria. The PPV for HPV-vaccinated women undergoing either LBC or HR-HPV screening were not statistically different. However, similar to papers in the current literature, HG dyskaryosis (HGD) PPVs of both techniques did not meet the PHE threshold of 76.6-91.6% outlined in the cervical standards data report.