Abstract
Simple SummaryThis 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 log10 GE/103 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. 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 log10GE/103 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/log10GE/103 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.
Highlights
High-risk HPVs have been recognized as the etiologic agents of cervical cancer [1,2]
Cervical smears positive for High-risk HPV (hrHPV) were further tested for HPV16 and HPV18 VL, the two most prevalent HPV in cervical cancers, using homemade real-time PCRs [25]
Four hundred eighty-three women with a cervical high-grade lesion at the first visit, 47 women having had a previous history of high-grade lesion and 687 women with no follow-up visit (FU) at the Gynecology Clinic of Besançon’s Hospital were excluded from the analysis
Summary
High-risk HPVs (hrHPV) have been recognized as the etiologic agents of cervical cancer [1,2]. Only persistent infections confer an increased risk of developing precancerous and cancerous lesions [3,4]. Among the twelve HPV genotypes having oncogenic properties, HPV16 is the most at risk, causing cancer of the cervix and at several other sites [5]. HPV16, HPV18 is the second most prevalent hrHPV in cervical cancer [6,7,8] and both HPV types have been associated with a high ten-year risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) [9]. Cervical cancer screening has been based on cytological analysis of cervical smears since the 1950s. HrHPV testing has been proposed as a potential alternative to repeated cytology or immediate colposcopy for the triage of women with
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