To identify risk factors for progression of intraepithelial cervical lesions, 190 women with invasive cervical cancer were compared with 75 women with in situ disease diagnosed in Bangkok, Thailand, between September 1991 and September 1993. Polymerase chain reaction-based assays for type-specific human papillomavirus (HPV) DNA in cervical scrapings revealed oncogenic types in 79% of invasive and 57% of intraepithelial tumors. Types 16 and 18, but not types 31/33/35/39, were more common in invasive than intraepithelial tumors, and untyped HPV DNA was found more commonly in the in situ lesions, suggesting that in situ disease is four times more likely to become invasive if due to type 16 or 18 than to other causes, and that tumors with only untyped HPV are not at increased risk of progression. After controlling for HPV type, the risk of developing invasive diseases, compared with the risk of developing intraepithelial lesions, was not related to any of a large number of sexual and hormonal factors considered or to smoking, suggesting that any cofactors these variables represent act before the development of in situ carcinoma. Two indices of socioeconomic status were associated with a reduced risk of only invasive disease, suggesting the existence of unknown protective factors that operate after intraepithelial lesions develop.
Between September 1991 and September 1993, husbands of women with and without cervical neoplasia and commercial sex workers in one brothel and one massage parlor in Bangkok, Thailand, were interviewed; serologic tests for sexually transmitted infections were performed; and cervical and penile scrapings were tested for human papillomavirus (HPV) DNA. The risks of cervical carcinoma in monogamous women and of oncogenic HPV in their husbands were associated with the men's having unprotected intercourse with prostitutes. The prevalence of oncogenic HPV was higher in commercial sex workers than in women attending gynecologic and family planning clinics. Oncogenic HPV prevalence declined with age in human immunodeficiency virus (HIV)-negative, but not in healthy HIV-positive, commercial sex workers and was weakly associated with hepatitis B antigenemia, suggesting that persistence of HPV infection is due to subtle changes in immunity. Associations of HPV with recent pregnancy and oral contraceptive use suggest that hormonal factors may increase the risk of cervical neoplasia by enhancing persistence of HPV infection. The prevalence of high-grade squamous intraepithelial lesions was strongly related to oncogenic HPV types and weakly to HIV infection only in their presence. Commercial sex workers in Bangkok are reservoirs of oncogenic HPV, and cervical cancer in monogamous Thai women develops in part as a result of transmission of these viruses to them by their husbands from prostitutes.
Personal interviews, tests for antibodies to herpes simplex virus type 2, Treponema pallidum, and hepatitis B, tests for hepatitis B surface antigen (HBsAg), and polymerase chain reaction-based assays for human papillomavirus (HPV) DNA in cervical scrapings were obtained from 190 women with squamous cell and 42 women with adenomatous cervical carcinoma and from 291 hospitalized controls diagnosed in Bangkok, Thailand, between September 1991 and September 1993. Risk was strongly associated with oncogenic HPV types, with types 16 and 18 predominating in squamous and adenomatous lesions, respectively. The 126 cases with HPV-16 and the 42 cases with HPV-18 were compared with 250 controls with no evidence of any HPV. The risk of both viral tumor types increased with decreasing age at first intercourse in this predominantly monogamous population, which may be explained by more visits to prostitutes by the husbands of cases with early than late age at first intercourse. HPV-16 tumors were weakly associated with HBsAg carrier state and smoking. The risk of tumors of both viral types increased with parity and use of oral contraceptives but not with injectable progestogens. Factors that may predispose to persistent, oncogenic HPV-16 or -18 infection may include estrogens or progestins in the presence of estrogens, immunosuppression, and smoking, but other factors related to low socioeconomic status are also involved.
Increasing intake of foods rich in total vitamin A, and particularly high-retinol foods, may reduce risk of in-situ cervical cancer, and at the highest level of intake may inhibit progression to invasion. If others confirm these results they suggest means of reducing the risk of cervical cancer that are amenable to public health action.
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