(2)子宮頸部初期病変におけるヒトパピローマウイルス(HPV)感染と免疫マーカー(講演要旨,<特集>第58回シンポジウム3「子宮頸部初期病変の管理と治療-標準化をめざして」)

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Human papillomavirus (HPV) infection is the most important causative factor for cervical cancer. Our studies aimed to clarify the natural history of HPV infection for cervical cancer from an aspect of host immunity against HPV. We have recently conducted an epidemiological study of HIV and cervical cancer in women visited to a health center in Nairobi, Kenya, and 31% of participants were HIV positive. HIV-positive women had 4.5 fold more high-risk HPV infection, and 6.8 fold more multiple HPV type infection than in HIV-negative women. Cytological examination revealed that high-grade squamous intraepithelial lesions (HSIL) was 20 fold more in HIV-positive women than in HIV-negative women. Immune suppression by HIV appears to allow HPV infection and to promote malignant progression of HPV-infected cervical cells. When we examined the levels of serum or cervical-secreted HPV L1 antibody, elicited HPV L1 antibody was HPV type specific, and induced in women who had persistent HPV infection. However, presence of the antibody was not correlated with present status of HPV infection. The lymphocyte proliferative response against HPV16 E2 was observed only in the women who cleared HPV16, while neither in the control women nor women who had persistent disease. Furthermore, the lymphocytes of the women who cleared HPV infection produced high amount of Th-1 cytokine IFN-γ, in vitro suggesting that cell mediate immunity is likely to eliminate HPV. Polarized helper T type 1 (Th-1) and type 2 (Th-2) responses were observed in women who are infected with HPV. However, the polarization was seen in women haying HPV-infected normal cervices and CIN-1, whereas such responsedel was not observed in women having higher grade CIN (CIN-2/CIN-3). Simultaneous activation of Th1 and Th2 response appears to be elicited in malignant lesions, although the mechanism is unknown. Such aberrant immune status may reduce immune responses against HPV, or may represent enhanced immune responses against malignant cells which acquired resistance to HPV-specific immunity. Serum cytokine levels may not represent local immune status, since many cytokines are limited to be released into the blood. Then we investigated serum levels of chemokines, which attract lymphocytes from lymph nodes to inflamed areas. Serum level of Th1 inducible chemokine, IP-10 was higher in cervical cancer than in normal and CIN. IP-10 was more released according to increasing clinical stage of cervical cancer. IP-10 appears to be released at danger, and it might be a good marker for predicting malignant condition.
社団法人日本産科婦人科学会の論文
2006-11-01

(2)子宮頸部初期病変におけるヒトパピローマウイルス(HPV)感染と免疫マーカー(講演要旨,<特集>第58回シンポジウム3「子宮頸部初期病変の管理と治療-標準化をめざして」)

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