LONDON – Women with systemic lupus erythematosus (SLE) have more than twice the risk of developing cervical neoplasia than do women in the general population, according to the results of a large Swedish registry study.
The study’s results indicate that the highest risk for cervical dysplasia or invasive cancer occurred among women with SLE who were using immunosuppressive agents, compared with those on antimalarial medication.
The results highlight the importance of women with SLE attending cervical cancer screening appointments, according to the researchers, who are from the Karolinska Institute in Stockholm, Linköping (Sweden) University, and Stanford (Calif.) University.
“At this time, we cannot comment on whether changes to screening programs are necessary, especially given there are considerable differences in cervical screening between countries,” lead study author Dr. Hjalmar Wadström said in an interview ahead of the study’s presentation at the European Congress of Rheumatology.
Dr. Wadström, who is an MD-PhD student at the Karolinska Institute working under the supervision of Dr. Johan Askling, explained that SLE is associated with various immunologic aberrations and is typically treated with immunomodulatory regimens. These regimens, however, have been linked to an increased risk of cervical neoplasia.
“Therefore, determining the risk among women with SLE is of direct clinical relevance,” he said. “Cervical cancer screening is important in the prevention of cervical cancer.”
To date, there have been few studies looking at the topic, and, as SLE is a relatively rare disease and the development of cancer is a relatively rare outcome, the study aimed to better estimate the risk.
Data from national Swedish patient and pharmacy registers were used to assemble a cohort of almost 5,000 women with SLE and a matched cohort of more than 28,000 women without SLE from the general Swedish population. The average age at the start of follow-up was 51 years, and about 40% of women were taking oral corticosteroids.
A total of 121 events occurred in the 4,550 women with SLE over the course of 23,136 total follow-up years. In comparison, there were 336 events in the 28,113 women without SLE from the general population over the course of 155,543 total years of follow-up.
This produced a hazard ratio for cervical neoplasia in women with SLE versus those without of 2.12 (95% confidence interval, 1.65-2.71). The analysis was adjusted for multiple confounding factors, including family history of cervical cancer and prior cervical screening in the 5 years before the start of follow-up.
Dr. Askling, who presented the findings during a press conference at the meeting, noted that just 5 of the 121 events seen in the overall SLE cohort were invasive cancers and the other events were premalignant changes, which included cervical intraepithelial neoplasia (CIN) stage 1, 2, and 3. “This is as it should be in the population; most events that you pick up in a screening program are premalignant,” he said.
Within the SLE cohort, two subcohorts of women also were identified: those taking hydroxychloroquine (n = 1,783) and those taking immunosuppressive drugs (n = 1,981). One of the reasons for looking at this is that treatment may serve as a proxy for the severity of disease, Dr. Wadström explained.
“SLE is a heterogeneous disease with numerous phenotypes that span from mild to life-threatening systemic disease,” he said. “Patients treated with an antimalarial, with or without oral steroids exclusively, tend to represent less severe cases, while more severe manifestations and organ involvement may necessitate potent cytotoxic immunosuppressive therapy.”
Adjusted HRs for cervical neoplasia in women with SLE were 1.52 (95% CI, 1.00-2.33) for those taking antimalarial therapy and 2.72 (95% CI, 2.01-3.67) for those taking immunosuppressive drugs, compared with women in the general population. The hazard ratio for cervical neoplasia comparing women with SLE taking immunosuppressive drugs with those taking antimalarial medication was 1.83 (95% CI, 1.15-2.91).
So what does this mean for clinical practice?
“We think it’s important that women with SLE, especially those with severe disease who are being treated with systemic immunosuppressants, attend cervical screening,” Dr. Wadström said.
Dr. Askling commented that, thankfully, women with SLE seemed to be just as adherent to attending cervical screening appointments as women in the general population. He noted it was important for clinicians to recognize that women with SLE do appear to have an increased risk for cervical changes and to ensure that they understand the need for continued adherence. “We don’t think at this stage that any additional measures should be taken,” he said.
But should all women with SLE be vaccinated against infection with the human papillomavirus, a known cause of cervical cancer? Dr. Asking said that since the women in the current study were in their 50s, it is not clear if such a move would be of benefit, certainly not when compared with vaccinating younger women. “Yes, we remember vaccination,” he said. “No, it doesn’t solve the problem for now, it solves the problem for the future.”