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The natural history of squamous cancer of the uterine cervix resembles that of a sexually transmitted disease (Kessler II, 1976). Potential aetiological agents include the transforming members of the human papillomaviruses, in particular HPV types 16 and 18, since a high proportion of patients with cervical intraepithelial neoplasia (CIN) and invasive carcinoma of the cervix are infected with these HPV types (zur Hausen, 1987; Cornelisson et al., 1989). In contrast, the prevalence of HPV 16 based on rigorous polymerase chain reaction (PCR) studies in women with no evidence of cervical disease is between 5-17% (Van den Brule et al., Bavin et al., 1992). Complementary to the epidemiological investigations linking HPV 16 and cervical cancer, in vitro studies have shown that HPV 16 is capable of immortalising transformed cell lines through the E6 and E7 protein products binding to the cellular tumour suppressor genes p53 and plO5RB respectively (Dyson et al., 1989;. Recent data (Crook et al., 1992) have shown that in women with cervical carcinoma, mutations in p53 and the presence of HPV 16 or 18 DNA are mutually exclusive, thus confirming similar data obtained from analysis of established cervical cancer cell lines (Crook et al., 1991;.In addition to a possible role in the aetiology of cervical carcinoma, the presence of HPV 16 DNA may be of use as a prognostic marker of high-grade cervical disease, i.e. CIN 2 and CIN 3. Previous work in our laboratory (Bavin et al., 1992) has shown that the presence of HPV 16 DNA is useful in identifying women with high-grade cervical disease within a general practice population with an associated relative risk of 5.67. In addition, the combination of cytology and HPV 16 positivity identified more women with significant disease than either screening method alone. However, the clinical setting which would most benefit from a prognostic marker of high-grade cervical disease is in the large number of women referred for colposcopy with a smear suggesting mild dyskaryosis. We have previously shown (Giles et al., 1989) that approximately one third of these women will have high-grade disease whilst the remainder will have either CIN 1 or be colposcopically normal. A mechanism to differentiate women with high-grade disease within such a referral population would have a significant impact on targeting colposcopic resources to those individuals at high risk.Recent use of a semi-quantitative PCR method (Cuzick et al., 1992) has suggested that the presence of high or intermediate quantities of HPV 16 DNA in cervical scrapes is useful in identifying women with high-grade cervical disease within populations referred with a mild or moderately dyskaryotic smear. However, it should be noted that the data provided for the population referred with a mildly dyskaryotic smear contained relatively small numbers of women (23 in total). Therefore, we report here the qualitative and semi-quantitative PCR assessment of HPV 16 DNA in a population of 200 women referred with a smear suggesting mild dyskaryosi...

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Two hundred asymptomatic women in a general practice were screened both cytologically and colposcopicaliy for evidence of cervical intraepithelial neoplasia. The prevalence detected by cytology alone was 5%, but the prevalence detected by cytology and colposcopy together was 11%. None of the larger lesions of cervical intraepithelial neoplasia (affecting more than two quadrants of the cervix) was associated with negative cytology.The false negative cytology rate for smaller lesions was 58%.The clinical importance of the smaller lesions that were not accurately detected by cytology screening is unknown. As these lesions affected 6% of the screened population further studies of their clinical course are urgently required. Local destructive treatment in such cases may represent considerable overtreatment. If these lesions prove to be clinically important, however, the results of this study predict an increasing epidemic of preinvasive and invasive disease of the cervix.

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