Papillomaviruses in lesions of the lower genital tract in Israeli patients

Human papillomaviruses (HPVs) have been strongly associated with benign lesions of the genital tract (condylomata) and with genital cancer of the vulva and cervix. Since the incidence of these lesions in Israel is considered to be low, we have studied the presence of HPV 6, 11, 16 and 18 DNAs in benign, premalignant and malignant tissue samples or gynecological swabs of the lower genital tract. HPV sequences were detected in 48 out of 66 condylomatous lesions (72%), 5/11 grades I-II intraepithelial neoplasia (45%), 4/6 grade III intraepithelial neoplasia (carcinoma in situ) (66.6%) and 8/22 invasive carcinoma (36%). The latter included six cases of vulvar carcinoma which were all negative for HPV sequences. No additional HPV types could be detected in any of the tissue biopsies examined. HPV 18 DNA has been found in one vulvar condyloma where it persisted as an episomal molecule, this being the first report of that specific viral DNA in a condylomatous lesion. In all the benign and premalignant lesions containing HPV, the viral sequences were maintained in an episomal state. In two cases of invasive carcinoma, the HPV 16/18 related sequences were integrated in the cellular genome, but in five cases (three containing HPV 16/18 related DNAs and two containing HPV 6/11 related DNAs) the viral sequences were episomal. HPV 16/18 related sequences detected in one out of three cases of vaginal carcinoma were also found to be episomal. This data indicates that human papillomavirus sequences are indeed found in genital lesions of Israeli patients, although to a lesser extent than in other countries, especially for benign lesions and invasive carcinomas. Although HPVs may have a causative role in the development of genital lesions, also in this low tumor incidence area, other factors should be also considered in the etiology of these lesions.