To identify the risk factors for cervical intraepithelial neoplasia (CIN), we reanalysed the data from our previous case -control study by adjusting for human papillomavirus (HPV) antibodies. Unlike our previous study based only on HPV DNA, smoking and Chlamydia trachomatis infection were revealed as significant risk factors for CIN after adjustment for HPV antibodies. Infections by oncogenic human papillomaviruses (HPVs) are established as a major risk factor for cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC). However, only a fraction of infected women develop cervical cancer, suggesting the involvement of additional cofactors in cervical carcinogenesis. In numerous case -control studies various epidemiological factors have been suggested as relevant to CIN and ICC, although the results from these studies have not been entirely consistent (Schiffman and Brinton, 1995). In epidemiological studies of risk factors for CIN and ICC, it is of great importance to allow for the strong effect of HPV infections. To determine HPV exposure among cases and controls, most studies have used HPV DNA testing, while recent studies have employed HPV capsid serology. However, it has not been determined whether the different measurements of HPV exposure can affect conclusions from case -control studies.To address this issue, we reanalysed the data from our previous case -control study of CIN by adjusting for HPV DNA and antibodies.
MATERIALS AND METHODSThe present study was conducted on women who previously participated in a Japanese case -control study of CIN. The details about this case -control study have been provided elsewhere (Yoshikawa et al, 1999). Among a total of 167 pairs, serum samples from 26 cases and 58 controls were not available for HPV capsid serology. Therefore, the present analysis was restricted to 250 subjects consisting of 141 cases (80 CIN I, 34 CIN II and 27 CIN III) and 109 controls that were tested for both cervical HPV DNA and serum HPV antibodies. The distributions of study variables in the excluded/included cases and controls were similar. We examined HPV DNA in cervical samples by polymerase chain reaction (PCR) using consensus primers for the HPV L1 region (Yoshikawa et al, 1999). Detection of IgG antibodies to HPV16, 52 and 58, the most frequently detected HPV types in Japan, was performed by enzyme-linked immunosorbent assay (ELISA) using purified L1-capsids (virus-like particles (VLPs)) as antigens (Matsumoto et al, 2003). In addition, the level of IgG antibodies to Chlamydia trachomatis was determined by using an enzyme immunoassay (EIA) kit (Thermo Labsystems, Vantaa, Finland) that does not detect antibody to Chlamydia pneumoniae. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by a logistic regression analysis. The analysis was carried out using JMP 4.0J statistics package (SAS Institute, Cary, NC, USA). The P-values obtained in all tests were considered significant at o0.05.
RESULTSHuman papillomavirus status among cases and control...