Linear array genotyping and hybrid capture II assay in detecting human papillomavirus genotypes in women referred for colposcopy due to abnormal Papanicolaou smear

Abstract

Summary: The main objective of this study was to assess the feasibility of human papillomavirus (HPV) genotyping in women referred for colposcopy due to abnormal Papanicolaou (Pap) smear. A series of 248 women referred for colposcopy due to an abnormal Pap smear were analysed with the Roche Linear Array HPV genotyping test detecting 37 most frequent HPV types, and compared with hybrid capture II (HCII) assay for oncogenic (high-risk [HR] HPV) types as well as for p16INK4a expression using immunocytochemistry. All tests were performed in cervical samples collected in PreservCyt® liquid media for liquid-based cytology (ThinPrep), and colposcopic biopsy and/or loop electro excision procedure cone biopsy was used as the gold standard. HPV16 was the single most frequent genotype (29/258; 11.7%), followed by HPV51 (4.4%), HPV66 (3.6%), HPV42, 52 and 56 (3.2% for all). Linear array genotyping test significantly predicts both abnormal colposcopy (odds ratio [OR] = 9.0; 3.12-25.93), high-grade squamous intraepithelial lesions (OR = 9.6; 1.26-74.17) and cervical intraepithelial neoplasia (CIN) 3+ (OR = 29.3; 3.95-218.06). In detecting CIN3, linear array was equivalent (97.6%) to colposcopy in sensitivity (SE), both being superior to HCII (92.7%). Concordance between linear array and HCII was moderate (Cohen's kappa κ = 0.547; 95% confidence interval [CI]: 0.435-659). Specificity (SP) and positive predictive value (PPV) of linear array were significantly improved, if only HPV16 genotype was considered. Performance in the best balance is obtained, when linear array and colposcopy are combined, giving 82.9% SE, 93.9% SP, 73.9% PPV and 96.3% negative predictive value (NPV) as predictor of CIN3+ (OR 74.5; 95% CI: 27.36-202.72). In conclusion, linear array for HR-HPV is a highly sensitive test (97.6%) with high NPV (98.9%) in detecting CIN3+ lesions. HPV16 genotyping alone significantly improves SP and PPV of this test in management of women with abnormal cytology.