Performance of HPV Genotyping Combined with p16/Ki-67 in Detection of Cervical Precancer and Cancer Among HPV-Positive Chinese Women.

Women with positive high-risk human papillomavirus (hrHPV) need efficient triage testing to determine colposcopy referrals. Triage strategies of combining p16/Ki-67 with extended HPV genotyping were evaluated in this study. In total, 899 women attending cervical cancer screening program and 858 women referred to colposcopy from five hospitals were recruited. All the participants were tested by HPV assays and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women with any abnormal results. HPV genotypes were divided into four strata (HPV16/18, HPV31/33/58/52, HPV45/59/56/66, and HPV51/39/68/35) according to their risks for cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The positive rates of four genotype strata among CIN3+ women were 3.47% (HPV51/39/68/35), 7.73% (HPV45/59/56/66), 14.7% (HPV31/33/58/52), and 78.1% (HPV16/18), respectively ( < 0.001). The positive rates of p16/Ki-67 increased with the elevation of HPV risk hierarchical from 65.0% in HPV51/39/68/35-positive women to 88.0% in HPV16/18-positive women ( < 0.001). p16/Ki-67 was an effective method for risk stratification of CIN2+ among HPV31/33/58/52- and HPV45/59/56/66-positive women [HPV31/33/58/52: OR for dual stain+ (OR) of 26.7 (16.8-42.4) and OR for dual stain- (OR) of 3.87(1.89-7.91); HPV45/59/56/66: OR of 10.3(5.05-21.0) and OR of 1.27(0.38-4.26)]. The combination of HPV16/18 genotyping and p16/Ki-67 triage of HPV31/33/58/52/45/59/56/66-positive women resulted in a lower referral rate (40.1% vs. 41.3%; < 0.001) as compared with triage of 12 other HPV-positive women with p16/Ki-67, although sensitivity and specificity levels for these two strategies were identical. Combining HPV extended genotyping and p16/Ki-67 can be considered as a promising strategy for cervical cancer screening and triage.