Smoking and cervical cancer: pooled analysis of the IARC multi-centric case–control study

Background: Smoking has long been suspected to be a risk factor for cervical cancer. However, not all previous studies have properly controlled for the effect of human papillomavirus (HPV) infection, which has now been established as a virtually necessary cause of cervical cancer. To evaluate the role of smoking as a cofactor of progression from HPV infection to cancer, we performed a pooled analysis of 10 previously published case–control studies. This analysis is part of a series of analyses of cofactors of HPV in the aetiology of cervical cancer. Methods: Data were pooled from eight case–control studies of invasive cervical carcinoma (ICC) and two of carcinoma in situ (CIS) from four continents. All studies used a similar protocol and questionnaires and included a PCR-based evaluation of HPV DNA in cytological smears or biopsy specimens. Only subjects positive for HPV DNA were included in the analysis. A total of 1463 squamous cell ICC cases were analyzed, along with 211 CIS cases, 124 adeno- or adeno-squamous ICC cases and 254 control women. Pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models controlling for sexual and non-sexual confounding factors. Results: There was an excess risk for ever smoking among HPV positive women (OR 2.17 95%CI 1.46–3.22). When results were analyzed by histological type, an excess risk was observed among cases of squamous cell carcinoma for current smokers (OR 2.30, 95%CI 1.31–4.04) and ex-smokers (OR 1.80, 95%CI 0.95–3.44). No clear pattern of association with risk was detected for adenocarcinomas, although the number of cases with this histologic type was limited. Conclusions: Smoking increases the risk of cervical cancer among HPV positive women. The results of our study are consistent with the few previously conducted studies of smoking and cervical cancer that have adequately controlled for HPV infection. Recent increasing trends of smoking among young women could have a serious impact on cervical cancer incidence in the coming years.