Human papillomavirus genotyping by a polymerase chain reaction-based genechip method in cervical carcinoma treated with neoadjuvant chemotherapy plus radical surgery

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Abstract
The aim of this study was to evaluate the accuracy of human papillomavirus (HPV) genotyping by a polymerase chain reaction (PCR)‐based genechip method and to determine the prognostic value of HPV genotype in bulky stage IB or IIA cervical carcinoma treated with neoadjuvant chemotherapy (NAC) and radical surgery. A total of 149 patients had adequate tissue for the study. The SPF1/GP6+ primers were used to amplify a 184 bp fragment. The amplimers were submitted for direct sequencing and hybridization with a genechip using revert‐blot detection of 39 types of HPV DNA in a single reaction. Two runs of PCR with respective hybridization were performed for each tumor. The complete concordance of HPV genotyping was 80.5% (120/149) of the paired genechip results. The kappa coefficient was 0.634 (P < 0.0001). HPV DNA sequences were detected in 100% of the specimens, among which 67.8% harbored single type and 32.2% contained multiple types. HPV‐16 was detected in 98.7%, HPV‐18 in 22.8%, HPV‐31 in 0.7%, HPV‐45 in 1.3%, HPV‐52 in 2.0%, HPV‐58 in 6.7%, HPV‐59 in 4.7%, and HPV‐67 in 0.7%. In multivariate analyses, the HPV genotype [HPV‐18 or HPV‐16 and HPV‐18 only versus all others: relative risk (RR), 2.33; 95% CI, 1.17–4.64; P = 0.016] and pre‐NAC tumor size (>5 versus ≤5 cm: RR, 2.25; 95% CI, 1.13–4.48; P = 0.021) were significantly related to overall survival. This PCR‐based genechip method is sensitive and reproducible for HPV genotyping. The association of HPV‐18 or HPV‐16 and HPV‐18 with poor outcome in cervical carcinoma treated with NAC plus radical surgery is confirmed.

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