Triaging HPV-positive, cytology-negative cervical cancer screening results with extended HPV genotyping and p16INK4a immunostaining in China

• Published in: BMC infectious diseases Vol. 21; no. 1; pp. 1 - 400
• Main Authors: Song, Fangbin, Yan, Peisha, Huang, Xia, Wang, Chun, Qu, Xinfeng, Du, Hui, Wu, Ruifang
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 30-04-2021; BioMed Central; BMC
• Subjects: Acetic acid; Algorithms; Biopsy; Cancer; Cancer screening; Cellular biology; Cervical cancer; Cervical cancer screening; Cervical intraepithelial neoplasia; Cervix; Clinical medicine; Clinical trials; Colposcopy; Cytology; Diagnosis; Genotype; Genotype & phenotype; Genotypes; Genotyping; HPV genotyping; Human papillomavirus; Identification and classification; Immunocytochemistry; Infections; Infectious diseases; INK4a protein; Inspection; Medical screening; Methods; p16 immunocytochemistry; p16 Protein; Papillomavirus infections; Sensitivity; Triage (Medicine); Womens health; China
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-021-06109-4

Self-sampling for human papillomavirus (HPV) testing is a feasible option to improve the cervical screening coverage. However, an ideal triage method for HPV-positive self-samples does not yet exist. The aim of this study was to explore the utility of HPV genotyping and p16.sup.INK4a immunostaining (p16) in triaging HPV-positive self-samples, focusing on HPV-positive, cytology-negative (HPCN) women. A total of 73,699 women were screened in a cervical screening project in China via SeqHPV assay on self-samples. HPV-positive women were called-back and collected cervical sample for p16 immunostaining and liquid-based cytology, those who met any result of HPV16/18+ or visual inspection with acetic acid (VIA) + or p16+ were referred for colposcopy, and HPCN women with adequate data on p16 and pathology were analyzed. A triage strategy was considered acceptable if the negative predictive value (NPV) for cervical intraepithelial neoplasia 3 or worse (CIN3+) was 98% or more, combined with an improvement of sensitivity and specificity for CIN2+/CIN3+ in reference to the comparator, being HPV16/18 + . A total of 2731 HPCN women aged 30-64 years were enrolled, 136 (5.0%) CIN2+ and 53 (1.9%) CIN3+ were detected. Five triage strategies met the criteria: p16+; HPV16/33+; 'HPV16+ or HPV33/58/31/35+&p16+'; 'HPV16/33+ or HPV58/31/35+&p16+'; HPV16/18/31/33/45/52/58 + & p16+. These strategies required less or similar colposcopy referrals, and less colposcopies to detected one case of CIN2+/CIN3+, achieving favorable false positive (negative) rates to the comparator. Among them, p16 staining detected 83.1% (79.2%) of underlying CIN2 + (CIN3+) in HPCN women. Moreover, three triage strategies were favorable in sensitivity and/or specificity to the 'HPV16/33+' strategy: p16+; 'HPV16+ or HPV33/58/31/35 + &p16+'; HPV16/18/31/33/45/52/58 + &p16 + . Genotyping for HPV16/33 could be utilized to optimize the management of HPCN women. Moreover, p16 immunostaining, either alone or combined with extended genotypes, is more effective than HPV genotypes alone in the triage of HPCN women.