Human papillomavirus infection and cervical lesions in rheumatic diseases: a systematic review

An association between immune-mediated diseases and cervical pre-malignant and malignant lesions is described, having the human papillomavirus (HPV) infection a causal role. Related studies have been generally focused on systemic lupus erythematosus (SLE) patients, but relatively to other diseases, such as rheumatoid arthritis (RA), Sjögren's syndrome (SS) and systemic sclerosis (SSc), data has not been systematically evaluated. We conducted a systematic review analysis of the literature in PubMed, including articles published until March of 2015, in patients with RA, SS, SLE and SSc, to evaluate the frequency of HPV infection, cervical dysplasia and cervical cancer, and associated factors, with particular interest on the role of glucocorticoids and immunosuppressive treatment. Moreover, safety and efficacy of HPV vaccines in these patients was investigated. Of 476 articles identified, 27 were finally included. The studies showed an increased prevalence of cervical dysplasia and cancer, with the HPV infection being an important associated factor, in particular in SLE patients. The data relatively to other rheumatic diseases was very scarse, but an increased prevalence of smear abnormalities was also found in RA. Patients exposed to glucocorticoids and to long-term immunosuppression, particularly cyclophosphamide, have increased risk of presenting more pre-malignant lesions than the general population. The available vaccines seem to be generally safe and immunogenic in the short- period evaluation, but long-term follow-up is required to evaluate the impact of the vaccine in the protection against HPV infection and occurrence of high-grade cervical lesions.