The independent prognostic value of HPV genotype is confirmed in this study. The prognostic models could be useful in counseling patients and stratifying patients in future clinical trials.
Our aim was to investigate the human papillomavirus (HPV) genotype distribution and correlation between HPV parameters and clinicopathological variables in cervical carcinoma treated in a large tertiary referral medical center in Taiwan. Consecutive patients treated for cervical carcinoma (Stages I-IV according to the International Federation of Gynecology and Obstetrics) between 1993 and 2000 were included. HPV genotyping using SPF1/GP61 PCR was performed, followed by hybridization with a genechip (Easychip 1 HPV Blot, King Car, Taiwan). E6 typespecific PCR was performed to validate multiple-type. HPV-negative samples were further verified by type-specific PCR and a repeat HPV Blot. A total of 2,118 patients were eligible for analysis. HPV DNA sequences were detected in 96.6% (95% CI, 95.8-97.4%) of the specimens, among which 82% harbored single-type and 18% contained multiple-type HPV sequences. Thirty-five types of HPV were identified and the leading 8 were HPV16 (50.0%), HPV18 (17.8%), HPV58 (16.3%), HPV33 (8.7%), HPV52 (6.8%), HPV39 (3.0%), HPV45 (2.5%) and HPV31 (2.3%). HPV58 or 33 or 52 was detected in 30.3% (641/2,118). By multivariate analysis, HPV58-or 33-or 52-infection was significantly associated with older age (p < 0.001) and primary radiotherapy or concurrent chemoradiation (RT/CCRT) (p < 0.001). Among HPV-positive cases, multiple-type was more frequently seen in those receiving primary RT/CCRT (p < 0.001). The knowledge of HPV genotype distribution will form a basis for guidelines in HPV-based cervical cancer screening and cost-effective multivalent HPV vaccine policy in Taiwan and in the world. The association between HPV parameters and clinicopathological variables warrants further investigations. ' 2007 Wiley-Liss, Inc.Key words: human papillomavirus; PCR; genotype; cervical cancer; genechip Cervical cancer is one of the most common female genital cancers worldwide.1 There is strong epidemiological and molecular evidence indicating that human papillomavirus (HPV) infection is a necessary event in the development of cervical intraepithelial lesions and subsequent invasive carcinoma.2-5 Anogenital HPVs have been divided into risk groups according to the frequency of their presence in cervical carcinoma. Low-risk HPV types include HPV6,11,40, 42, 43, 44, 54, 61, 70, 72, 81 and CP6108. High-risk HPV types are represented essentially by HPV16,18,31,33,35,39, 45, 51, 52, 56, 58, 59, 68 and 82 (MM4). The third group, called probably carcinogenic types, is represented by HPV26, 53 and 66. 2 With the advancement of technology such as polymerase chain reaction (PCR), the sensitivity of detecting HPV DNA has been possible for as low as 1-50 copies of virus in a sample. Several type-specific PCR primer sets and general (consensus) primer sets such as MY09/MY11 and GP51/GP61 are widely used. Although the sensitivity of in situ hybridization is limited, it permits localization of HPV DNA in the sample. 6 However, even with the combinations of type-specific and general primer sets, the sensitivity is li...
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