Evaluation of partial genotyping with HPV16/18 for triage of HPV positive, cytology negative women in the COMPACT study.

Objective: While cytology-based screening programs have significantly reduced mortality and morbidity from cervical cancer, the global consensus is that primary human papillomavirus (HPV) testing increases detection of high-grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the optimal triage strategy for HPV+ women to avoid over-referral to colposcopy may be setting specific. We compared absolute and relative risk (RR) of >CIN2/3 within 12 months of a negative cytologic result in women HPV16/18+ compared to those with a 12-other high-risk HPV (hrHPV) genotype to identify women at greatest risk of high-grade disease and permit less aggressive management of women with other hrHPV infections.

Methods: Participants were 14,160 women aged 25-69 years with negative cytology participating in the COMparison of HPV genotyping And Cytology Triage (COMPACT) study. Women who were HPV16/18+ were referred to colposcopy. Those with a 12-other hrHPV type underwent repeat cytology after 6 months and those with >abnormal squamous cells of undetermined significance went to colposcopy.

Results: Absolute risk of >CIN2 in HPV16/18+ women was 19.5% (95% CI=12.4%-29.4%). In women 25-29 years and HPV16+ it was 40.0% (95% CI=11.8%-76.9%). Absolute risk of >CIN3 in women HPV16/18+ was 11.0% (95% CI=5.9%-19.6%). For women 30-39 years and HPV16+ it was 23.1% (95% CI=5.0%-53.8%). Overall risk of >CIN2, >CIN3 in women with a 12-other hrHPV HPV type was 5.6% (95% CI=3.1%-10.0%) and 3.4% (95% CI=1.6%-7.2%) respectively. RR of >CIN2, >CIN3 in HPV16/18+ vs. 12-other hrHPV was 3.5 (95% CI=1.7-7.3) and 3.3 (95% CI=1.2-8.8), respectively.

Conclusion: Primary HPV screening with HPV16/18 partial genotyping is a promising strategy to identify women at current/future risk of >CIN2 in Japan without over-referral to colposcopy.

Trial Registration: Trial Registration: UMIN Clinical Trials Registry Identifier: UMIN000013203.