The ASCCP guidelines recommend referring non-16/18 high-risk human papillomavirus (HR-HPV) positive women with cytology ≥ASCUS (ASCUS+) to colposcopy. In low-resource areas without cytology, other screening methods are needed to triage HPV positive women. Using direct prospective evidence, our study compared the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in non-16/18 HR-HPV and HPV 16/18 positive women stratified by viral load versus cytology, and evaluated the risk of CIN2+ by type-specific HPV viral load.
Using China's SPOCCS1 cervical cancer screening cohort, where 1,742 women were screened by liquid-based cervical cytology and Hybrid Capture 2 (HC2) at five-year intervals from 2005 to 2014, all HC2 positive samples were genotyped. Semi-quantitative viral load was measured by HC2 relative light units, with categories of low (1-9.99), moderate (10-99.99), and high (≥100) viral loads. Kaplan-Meier methods were used to estimate the ten-year cumulative incidence rate (CIR) of CIN2+ among pooled and type-specific HR-HPV women with baseline low, moderate and high viral loads, or ASCUS+.
Among the 209 HR-HPV positive women at baseline, the highest CIR of CIN2+ were for women infected with HPV 16/18 (N=38/57), HPV 16 (N=36/57), non-16/18 HR-HPV (N=19/57), HPV 31(N=7/57), and HPV 58 (N=7/57). Any HR-HPV, HPV 16/18, non-16/18 HR-HPV or HPV 16 positive women had significantly higher CIRs of CIN2+ at moderate or high viral loads than at low viral loads. Similar trends were observed for HPV 18, 31, 33, 52, and 58 positive women, but limited sample sizes prevented reaching statistical significance. For HPV16/18 women, the CIR of CIN2+ with ASCUS+ was 55.8% (95%CI: 42.2-67.4%) and CIRs with low, moderate, and high viral loads were, respectively, 25.7% (95%CI: 9.3- 46%), 43.2% (95%CI: 26-59.3), and 62.6% (95%CI: 40.6-75.5%). For non-16/18 HR-HPV women, the CIRs of CIN2+ at low and moderate viral loads were, respectively, 5.1% (95%CI: 0.9-15.2%) and 18.2% (95%CI: 21.6-54.9). The CIR of CIN2+ for non-16/18 HR-HPV positive women with ASCUS+ was 34.6% (95%CI: 21.9-47.6%) and comparable to that of non-16/18 HR-HPV high viral load (37.8%, 95%CI: 21.3-54.3%) (P>0.05).
HPV16/18 and non-16/18 HR-HPV viral loads could predict the ten-year CIR of CIN2+. HPV16/18 positive women should be directly referred to colposcopy regardless of viral load, as those with even a low viral load had a notably high risk of CIN2+. For non-16/18 HR-HPV women, using a viral load cutoff of ≥100 RLU had a comparable CIR of CIN2+ compared to ASCUS+ and presents a valuable triage tool for non-16/18 HR-HPV women in areas where cytology is not readily available.