Human papillomavirus viral load as a useful triage tool for non-16/18 high-risk human papillomavirus positive women: A prospective screening cohort study

Objective ASCCP cervical cancer screening guidelines recommend triaging high-risk human papillomavirus (hrHPV) positive women with cytology and genotyping, but cytology is often unavailable in resource-limited areas. We compared the long-term risk of cervical cancer and precancers among type-specific hrHPV-positive women triaged by viral load to cytology and visual inspection with acetic acid (VIA). Methods A cohort of 1742 Chinese women was screened with cytology, VIA, and Hybrid Capture 2 (HC2) test and followed for ten years. All HC2-positive samples were genotyped. Viral load was measured by HC2 relative light units/cutoff (RLU/CO). Ten-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) for type-specific hrHPV viral load was estimated using Kaplan-Meier methods. Results Baseline hrHPV viral load stratified by specific genotypes was positively correlated with prevalent cytological lesions. Ten-year CIR of CIN2 + was associated with cytological lesions and viral load. Among HPV 16/18-positive women, ten-year CIR of CIN2 + was high, even with normal cytology (15.3%), normal VIA (32.4%), viral load with RLU/CO < 10 (23.6%) or RLU/CO < 100 (33.8%). Among non-16/18 hrHPV positive women, ten-year CIR of CIN2 + was significantly stratified by cytology grade of atypical squamous cell of undetermined significance or higher (2.0% VS. 34.6%), viral load cutoffs at 10 RLU/CO (5.1% VS. 27.2%), at 100 RLU/CO (11.0% VS. 35.5%), but not by VIA (19.1% VS. 19.0%). Conclusions Our findings support the guidelines in referring all HPV16/18 positive women to colposcopy and suggest triaging non-16/18 hrHPV positive women using viral loads in resource-limited areas where cytology screening was inaccessible.