High-Risk and Multiple Human Papillomavirus Infections Associated with Cervical Abnormalities in Japanese Women

Toshiyuki Sasagawa, Walid Basha, Hiroshi Yamazaki, and Masaki Inoue


To estimate the risk of human papillomavirus (HPV) infection for cervical malignancies, we conducted a case-control study in Japan. Abnormal cervical cell (366) and normal cell samples (1562) were tested for the presence of HPV DNA using a new PCR-based test (LCR-E7 PCR). When single HPV infections were considered, 26 different HPV types were identified in normal cervices and in low-grade squamous intraepithelial lesions (LSIL); whereas HPV-16, -18, -31, -33, -35, -45, -51, -52, -56, -58 and -67 were detected in high-grade squamous intraepithelial lesions (HSIL) and in squamous cell carcinoma (SCC) of the cervix, and HPV-16 and -18 were detected in cervical adenocarcinoma. HPV-6 and -11 were detected in condyloma acuminatum tissue. In HSIL and SCC, HPV-16 was the most prevalent type and HPV-51, -52, and -58 were the next most prevalent; whereas HPV-39, -59, and -68 were not detected. Analysis by odds ratio (OR) revealed that HPV-11, -39, -42, -44, -53, -59, -62, and -66 (HPV-66: OR,139; 95% confidence interval (CI) =  6.7–168) were associated with LSIL; HPV-16, -18, -31, -51, -52 and -58 (HPV-16: OR, 69; 95%CI = 36–131) were associated with SCC; and HPV-16 and -18 (OR, 94; 95%CI= 28–317) were associated with adenocarcinoma. Multiple HPV infection was associated with LSIL (OR, 24; 95% CI= 13–44), HSIL (OR, 16; 95%CI= 8.4 –32), and SCC (OR, 8.3; 95%CI = 3.2–22), although the prevalence decreased with the grade of the lesions. All results suggest that HPV-6 and -11 are condyloma types, HPV-16, -18, -31, -51, -52, -58, and perhaps -33, -35, -45, -56, and -67, are the high-risk HPV types, and many other types are LSIL associated types in Japan. HPV typing and detection of multiple HPV infections in clinical samples may be useful as surrogate markers for cervical cell abnormalities.

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