Human papillomavirus infection in systemic rheumatic disorders: Current concepts, challenges and expectations

Abstract

There is strong evidence that women with systemic rheumatic disorders, particularly systemic lupus erythematosus (SLE) have an increased risk for developing cervical cancer. Several epidemiological studies have shown causal relationship between human papilloma virus (HPV) infection and cervical neoplasia in general population, nevertheless; information about the impact of HPV infection in women with rheumatic disorders treated with immunosuppressive drugs or biologic therapy is still evolving. HPV infection is more frequently observed in some rheumatic systemic diseases mainly in SLE with relevant data available. Prevalence figures in SLE for HPV infection vary from 11.8% to 54%. Recently, our group reported in Mexican women with SLE, HPV infection is 14.7%, a figure that is important for Latin America where cervical cancer is highly prevalent. Longitudinal designs have been rarely performed; one study reported an increase in frequency of HPV infection from 12.5% to 25% after 3 years of follow-up. In SLE there is a high frequency of infection with several type of virus (around 17%), most of them considered as high-risk virus for cervical neoplasia. Data in African American women with SLE show that around 3% have high-grade squamous intraepithelial lesions (HSIL) and 1.2% cervical cancer. Epidemiological studies of HPV infection in other rheumatic diseases are infrequent; our group reported HPV infection in 31% of the rheumatoid arthritis (RA) patients, whereas others reported 3% in Sjögren syndrome. Although common risk factors such as age, occupation, lifetime sexual partners, other sexually transmitted co-infections, or early age at first intercourse, are related with HPV; in rheumatic disorders the association between HPV infection with utilization of immunosuppressive drugs or with longer duration of treatment with corticosteroids but with no disease activity is relevant. Some immune abnormalities induced by the treatment have been associated with an increased frequency of HPV, where lower levels of B lymphocytes and NK cells in peripheral blood are observed in SLE under treatment with immunosuppressive drugs. TNF-α is involved in signaling apoptosis in infected cells, participating in the inhibition of viral replication, therefore TNF inhibitors may theoretically increase the risk for persistent infection but data supporting this hypothesis are still insufficient. HPV immunization with recombinant vaccine is useful to prevent precancerous cervical lesions, although; some autoimmune adverse events have been developed after the vaccine application including Guillain-Barré, transverse myelitis, optic neuritis, multiple sclerosis or myasthenia gravis, and there are some rare case-reports of RA, SLE, mixed connective tissue disease, Sjogren syndrome, dermatomyositis and scleroderma developed after the vaccination. On counterpart, vaccination is safe in patients with inactive RA or SLE. No significant differences in seroconversion rates have been observed between users and non users of immunosuppressive drugs except for mycophenolate mofetil. In summary, HPV infection in rheumatic disorders is an exciting area for research and a future task is to design a clinical guide for preventive measures in these patients, as well as a strategy for follow-up and treatment in those patients who have HPV infection; particularly for those who receive immunosuppressive therapy or anti-TNF agents. © 2013 by Nova Science Publishers, Inc. All rights reserved.