Evaluation of p16INK4a immunocytology and human papillomavirus (HPV) genotyping triage after primary HPV cervical cancer screening on self-samples in China

Self-sampling for human papillomavirus (HPV) testing is an effective option to increase the cervical screening coverage. How to best triage HPV-positive self-samples remains controversial. Here, we evaluated the performance of a novel p16INK4a immunocytology approach (p16) and HPV genotyping in triaging HPV-positive self-samples. A cohort of 73699 women were screened via SeqHPV assay on self-samples. HPV-positive women who met any sequential positive result of HPV16/18 or VIA or p16 were referred for colposcopy. A triage strategy was considered favorable if the NPV for CIN3+ was ≥98%, combined with an improvement of sensitivity and specificity in comparison to the comparator, being the ‘ASC-US+’ triage and the guideline strategy (HPV16/18+ or ASC-US+). A total of 3510 HPV-positive women were included, 422 (12.0%) CIN2+ and 247 (7.0%) CIN3+ were identified. The positivity of p16 and ASC-US+ were 36.3% and 22.2%, respectively. p16 was more sensitive and less specific than ASC-US+ (P < 0.0001). However, when combined p16 with cytology or genotypes, two triage strategies were superior to the ‘ASC-US+’ strategy: p16 scored 3+; HPV16/33/58/31+ &p16+. Moreover, four strategies were favorable to the guideline strategy: ASC-US+ or p16+; LSIL+ or p16+; HPV16+ or p16+; HSIL+ or p16+ or HPV16+. These strategies achieved better balance between diseases detection and colposcopy referral. Our findings indicate the promising utility of p16 immunocytology via adjusting the staining score or serving as an ancillary tool to liquid-based cytology or combining with genotyping for the triage of HPV-positive self-samples, which promotes the precise screening of cervical cancer. •p16 immunocytology combined with HPV genotypes was an efficient triage strategy for HPV-positive self-samples.•p16 immunocytology could serve as an ancillary tool to liquid-based cytology for the triage of HPV-positive self-samples.•p16 immunocytology was an effective triage strategy for HPV-positive self-samples via adjusting the staining score.