HPV16 Load Is a Potential Biomarker to Predict Risk of High-Grade Cervical Lesions in High-Risk HPV-Infected Women: A Large Longitudinal French Hospital-Based Cohort Study

SIMPLE SUMMARY: This study aimed at assessing HPV16 and HPV18 viral loads to predict the development of cervical high-grade lesion. Among 885 women positive for hrHPV and presenting no or mild cytological abnormalities, HPV16 and HPV18 prevalence was 25.9% and 8.4%, respectively. Of those women, 135 developed a high-grade lesion during the follow-up. Considering an HPV16 viral load cut-off set at 3.2 log(10) GE/10(3) cells a subgroup of women at high risk of developing high-grade cervical lesion (HR = 2.67; 95% CI 1.80–3.97 p ≤ 0.0001) has been identified. Moreover, a composite score based on HPV16 load, cytology and hrHPV detection allowed for CIN2+ risk stratification. To conclude, HPV16 load is a relevant biomarker to identify women at high risk for developing precancerous lesions of the cervix. ABSTRACT: High-risk HPV (hrHPV) testing has been implemented as a primary screening tool for cervical cancer in numerous countries. However, there is still a need for relevant triage strategies to manage hrHPV positive women to avoid excessive referral to colposcopy. The objective of this study was to assess, in women infected by hrHPV and presenting no or mild cytological abnormalities, HPV16 and HPV18 viral loads to predict the development of cervical high-grade lesion. Among 2102 women positive for hrHPV, 885 had no lesion or mild cytological abnormalities at baseline and had at least one follow-up (FU) visit. HPV16 and HPV18 prevalence was 25.9% and 8.4%, respectively. Of those women, 15% developed a high-grade lesion during the FU. An HPV16 viral load cut-off set at 3.2 log(10)GE/10(3) cells permitted to identify a subgroup of women at high risk of developing high-grade cervical lesion (HR = 2.67; 95% CI 1.80–3.97; p ≤ 0.0001). No specific HPV18 viral load threshold could have been defined in regard to the present study. In multivariate analysis, HPV16 load (absence/log(10)GE/10(3) cells < 3.2 vs. ≥3.2), RLU/PC 239 (1–100 pg/mL vs. >100 pg/mL) and cytology (normal vs abnormal) were independently associated with a significant increased risk of high-grade lesion development and were used to construct the prognostic score. In conclusion, HPV16 load is a relevant biomarker to identify women at high risk for developing cervical precancerous lesions.