London, United Kingdom—Women with systemic lupus erythematosus (SLE) appear to have a higher risk for cervical cancer and premalignant cervical changes compared with women in the general population, according to the results of a large Swedish registry study presented at the 2016 annual meeting of the European League Against Rheumatism (EULAR). The highest risk was observed in women treated with immunosuppressive agents compared with those treated with antimalarial medications, the researchers also observed.
“We know that lupus and its immunosuppressive treatments may increase the risk for cervical neoplasia,” explained the study’s co-author, Johan Askling, MD, PhD, Professor, Department of Medicine, Karolinska Institute, Stockholm, Sweden. “These findings imply that women with SLE should be counseled that they are at increased risk and be screened for cervical neoplasia.”
Risk for Cervical Neoplasia Doubled
It is controversial whether the increased risk is driven by precancerous changes, treatment, or both of these factors, Dr Askling explained. SLE is associated with various immunologic abnormalities, and is typically treated with immunomodulatory agents, which are associated with increased risk for cervical neoplasia.
To evaluate the risk for cervical neoplasia across different treatment exposures in this patient population, data from the national Swedish patient and pharmacy registries were linked for a cohort of 4550 women with SLE, and matched with a cohort of women from the general Swedish population. Among these women, 1783 were treated with antimalarials, and 1981 with more aggressive immunosuppressive therapy; 686 women received no treatment or both treatments, and were categorized as “other.” For the purpose of this study, the antimalarial and immunosuppressive cohorts were compared.
“We compared the group taking antimalarials with the group taking immunosuppressives, because treatments may serve as a proxy for disease severity,” stated Dr Askling. “Patients treated with an antimalarial with or without oral steroids tend to represent less severe cases, whereas potent cytotoxic immunosuppressive therapy is generally used to treat more severe disease with organ involvement.”
Average patient age at the start of follow-up was 51 years, and approximately 40% of patients were taking oral corticosteroids. Overall, there were 121 cancer events: 66 were in situ, 50 were high-grade dysplasia, and 5 were invasive.
The rate for cervical dysplasia or invasive cancer in women with SLE was doubled compared with women in the general population (hazard ratio [HR], 2.12). The analysis was adjusted for multiple confounding factors, including family history of cervical cancer; cervical screenings in the 5 years before the start of follow-up and at the year of start; as well as education level, healthcare use, number of children, and marital status.
The adjusted HR for cervical neoplasia among women with SLE taking antimalarial drugs was 1.52 versus 2.72 for those using immunosuppressive therapies compared with the general population. The HR for cervical neoplasia in women with SLE using immunosuppressive versus antimalarial therapies was 1.83.
HPV Vaccination Should Be Considered
Despite the large national sample used in their study, Dr Askling noted that they were unable to identify any meaningful changes in risk with adherence to a national screening program. In addition, it was not possible to tease out whether the increased risk observed in the study was associated with more severe SLE or immunosuppressant therapy.
“Women with SLE are at increased risk of cervical neoplasia, and treatment with systemic immunosuppressive therapy is a marker of higher risk among women with SLE,” Dr Askling stated. “Women with SLE treated with immunosuppressive therapy should be screened for cervical neoplasia.”
The human papillomavirus (HPV) vaccine can prevent cervical neoplasia, and should be considered for younger women with SLE, panelists agreed.
“The main message of this study is that physicians should discuss the risk of cervical neoplasia with their lupus patients,” added press conference moderator João Fonseca, MD, Chairperson of the Abstract Selection Committee, EULAR. “We feared that this study would show that the risk increases with a decrease of screening and that would have been a clear message to encourage screening, but we didn’t find a decrease in screening. This study emphasizes that we should not forget about preventive efforts. As rheumatologists, we need to remember this risk of cervical cancer.”