Low dose combined oral contraceptives

relation between HIV infection and cervical dyskaryosis. They have used a novel approach which aims to avoid many of the biases surrounding this topic. However, the authors have concluded that the weight of evidence to date suggests a causal relation between HIV and cervical dyskaryosis. Despite the careful design of this study, I feel that this inference is not supported by the data they present, and that other explanations could account for the observed association. In Johnstone’s paper the odds ratio of having any degree of dyskaryosis in HIV infected women was 2.4 (95 YO CI 1.4-4.4), compared with women without HIV infection, matched for drug use, neighbourhood etc. This is not a strong association and in an observational study could certainly be the result of bias or residual confounding. Of particular relevance is the lack of information about human papillomavirus (HPV) infection in these women. HPV may be a confounder for the relation between HIV infection and the development of cervical dyskaryosis, as it could be related to the exposure and the outcome of interest. There seems little doubt that cervical dyskaryosis occurs predominantly in women with HPV infection. In addition, acquisition of HPV infection may be related to acquisition of HIV infection. Although it is assumed that most of this drug using cohort acquired their HIV infection through drug use, it is possible that some of them may have acquired it through sexual contact with other drug users. Also the risk of acquisition of HIV infection will be correlated with factors such as the frequency of injecting practices and the frequency of needle sharing. Women who inject more frequently are more likely to acquire HIV infection and in order to pay for their drug use may sell sex for drugs, thus increasing their risk of acquiring HPV infection, and thereby increasing their risk of developing cervical dyskaryosis. Unfortunately. this study design makes it impossible to determine the prevalence of HPV infection or other measures of sexual behaviour in these women. The association between smoking and lung cancer (typical OR 14), or that between hepatitis B and hepatocellular carcinoma (typical OR 100) are so large it is difficult to imagine how this could explained by an uncontrolled confounder. However, the small increase in dyskaryosis in HIV infected women (lower limit of 95% CI 1.4) makes it very difficult to conclude that this is evidence of an effect which could not be modified by further adjustment. As a result, I feel that it is still premature to suggest that there is strong evidence that HIV infection has an independent effect on the incidence of cervical dyskaryosis which is of clinical significance. HIV infected women who use or have used drugs have a high prevalence of dyskaryotic lesions, but so do women who use or have used drugs but who are HIV negative. The most persuasive study design to determine the effect of HIV infection on this relation would be a well designed prospective cohort study of HIV infected and uninfected women with adequate adjustment for potential confounding variables. The study would need to be of sufficient size and sufficient duration to demonstrate HPV acquisition (or at least a surrogate marker of this such as sexual behaviour) and the development of new dyskaryotic lesions. Although this may be an immensely difficult study to undertake, there would seem to be no other way of convincingly demonstrating the true relation between HIV infection and cervical dysplasia.