Performance of HPV genotyping and methylation as a triage strategy for HPV-positive women with normal or minimal cytological findings.

OBJECTIVE

High-risk human papillomavirus (HR-HPV) screening has increased colposcopy referrals, particularly for women with HR-HPV positivity but no intraepithelial lesion or malignancy (NILM) and those with atypical squamous cells of undetermined significance (ASC-US). A fraction of low-grade squamous intraepithelial lesions (LSILs) is associated with cervical intraepithelial neoplasia grade 2 or worse (CIN2+) during diagnosis. This study evaluated the ability of methylation ( ) to distinguish between <CIN2 and CIN2 + in HPV-positive women with NILM, ASC-US, and LSIL cytology. It also assessed the absolute CIN2+/CIN3 + risk of the triage strategies , HPV genotyping, and their combination and compared the clinical performance of each triage strategy.

METHODS

To improve cervical screening efficiency, risk stratification based on HPV genotyping and was used as a triage strategy.

RESULTS

distinguished between <CIN2 and CIN2 + with an area under the receiver operating characteristic curve (AUC) of 0.828. The CIN2 + risk for (+) was 36.2%, while that for (-) was 2.3%. HPV16/18 combined , (+) and (+), (-) and (+) with absolute CIN2 + risk was 41.2 and 35.1%, respectively, whereas (+) and (-), (-) and (-), absolute CIN2 + risk was 6.0 and 1.5%, respectively. Colposcopy referral rates for HPV16/18 or and HPV16/18 or ASC-US+ were 35.6 and 79.2%, respectively, with concordant sensitivities (90.2% vs. 87.8%,  > 0.999) and significant differences in specificity (70.5% vs. 21.8%,  < 0.001). The HPV16/18 or triage strategy required the least number of referrals to detect a CIN2 + at 3.9 (3.3-4.6).

CONCLUSION

HPV16/18 or as a triage tool in HPV-positive women with NILM, ASC-US, and LSIL cytology significantly reduced colposcopy referrals while maintaining sensitivity similar to that of HPV16/18 or ASC-US+.