Impact of differentiating between persistent and new infections on colposcopy referral in HPV-positive triage-negative women: results from the NTCC2 study

Background In cervical screening, human papillomavirus (HPV)-positive women at 1-year retesting are typically referred to colposcopy. Extended genotyping enables the assessment of how many of these women have new infections. This study estimates the impact of distinguishing persistent from new infections in an effort to reduce colposcopy referral. It also evaluates whether the new infection rate varies according to genotyping, cytology, and other biomarkers results. Methods We analyzed data from HPV-DNA-positive women at baseline in the NTCC2 trial genotyped with the Onclarity HPV assay. Eligible participants were Onclarity-positive women without baseline CIN2 + who had a cervicovaginal sample collected at least 10 months after baseline. Persistent infections were defined as cases with at least one common genotype between baseline and follow-up specimens. New infections were defined as cases positive for different genotypes at follow-up, with no baseline genotypes detected. Results Among 1,540 women included, 613 were Onclarity-positive at both baseline and 1-year retesting: 488 (79.6%) had persistent infections, while 68 (11.1%) had new ones. All the 11 CIN3 + cases identified at follow-up occurred in women with persistent infections. The new infection rate was significantly higher in women with baseline single-channel positivity (13.2% vs 5.5%, p = 0.0070), or p16/ki67-negative results (13.6% vs 7.4%, p = 0.0232), whereas cytology and E6/E7 mRNA findings showed non-significant effects. Conclusion Extended genotyping classified 11.5% of 1-year HPV-positive cases as new infections. As 1-year HPV positivity accounts for about 60% of first-level colposcopies, this corresponds to about 7% of colposcopies. Baseline single-channel positivity and p16/ki67-negative results may influence this proportion. Trial registration Clinicaltrials.gov registration number: NCT01837693, New Technology in Cervical Cancer 2 (NTCC2) study