Study of immunologic evasion of human papllomavirus (HPV) Against host immuno-ersponse in patient with cervical cancer

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We have recently established the system to detect DNA of most mucosal HPV types using PCR method, which is called LCR-E7 PCR method. Using this method, we tested the prevalence of HPV infection in clinical samples. More than 17 HPV types were identified in normal, condyloma and lower-grade squamous intraepithelial lesions (LSIL). Higher incidence of infection with multiple HPV types was observed in these benign lesions than in the malignant lesions such as high-grade squamous intraepithelial lesions (HSIL) and invasive cervical (ICCA). HPV 16, 18, 31, 33, 51, 52, 56, and 58 were detected as a single infection in HSIL and ICCA, suggesting these are high-risk types for cancer. HPV51, 52 and 58 were more prevalent, whereas HPV18, 33 and 56 were less prevalent in Japanese ICCA than that in the USA.We investigated an association between HLA class II types and susceptibility for cervical cancer or the high-risk HPV infection. Women with HLA DR3, 4 were more susceptible to the high-risk HPV infection, and women with HLA DR2, 3, 4, 5 or with DR2-DQw1, DR3-DQw2, DR5-DQw3 haplotypes were susceptible to cervical cancer. Interestingly, women with DR2, 3, 4, 5 showed higher titers of anti-HPV 16 antibodies that in women with the other HLA types. This suggests that up-regulation of Th2 type immuno-response inducing strong humoral immuno-response may occur in these women with DR2, 3, 4, 5. We surmised that those women may have weaker Th1 response that make susceptible to HPV infection and cervical cancer. Immunohistochemical analysis showed no specific expression patterns of both Th1 and Th2-related cytokines in some tissue samples of cervical cancer. It may be important to study much more samples for such cytokine responses to conduct certain conclusions.