NEW YORK (Reuters Health)—Women with rheumatoid arthritis (RA) are at increased risk for cervical intraepithelial neoplasia (CIN), and those taking a tumor necrosis factor (TNF) inhibitor are at increased risk of cervical cancer, according to a study from Sweden.
“Whether this (the increase in invasive cancers) was due to the TNF inhibitors, disease severity, or exposure to other drugs, is not clear,” first author Dr. Hjalmar Wadstrom told Reuters Health by email. “Compared to other settings, such as immune suppression in organ transplantation, the risks we observed are much lower.”
Dr. Wadstrom and colleagues conducted a national registry-based study of women with RA treated in Sweden between 1999 and 2012, comparing the 9,629 women who started a first TNF inhibitor with 34,984 biologics-naive patients and 300,331 women in the general population.
The researchers also reviewed national cervical cancer screening using the Swedish Cancer Registry, which collects information on Pap tests, both opportunistic and preplanned.
In comparison with the general population, women with RA who were not taking disease-modifying biologics had more cancer screenings (hazard ratio 1.08) and a higher risk of cervical intraepithelial neoplasia (CIN) grade 1 (HR 1.53), and CIN 2-3 (HR 1.39), but not of invasive cervical cancer (HR 1.09).
Risk of invasive cancer doubled (HR 2.10) in women taking TNF inhibitors compared with biologics-naive patients. Women on TNF inhibitors had no significant increased risk of CIN grade 1 (HR 1.23) but did have increased risk of CIN grade 2-3 (HR 1.36).
Dr. Seoyoung C. Kim of Brigham and Women’s Hospital and Harvard Medical School in Boston pointed out that the statistically significant increase in relative risks doesn’t correspond to large absolute risks. In a telephone interview, she said, “I’d hate to see people over-interpret these findings. The absolute risk for cervical cancer is very low.”
Although the study did not provide data on universal use of the human papillomavirus (HPV) vaccine, Dr. Kim pointed out, “With it, we can eradicate 80% to 90% of the high-risk cervical cancers. We can also continue monitoring patients with Pap tests.”
Concerning to Dr. Kim is that women likely to benefit from TNF inhibitors might think they could lower their relative risk for cervical cancer by not taking disease-modifying medications. “Relative risk can be deceiving when the absolute risk is very low,” she said.
“We agree that HPV vaccine, in addition to screening, is a good way of further decreasing the risk of cervical cancer, irrespective of RA and TNF inhibitors, though different countries use different primary prevention programs,” Dr. Wadstrom told Reuters Health. “We also agree that it would be unfortunate if women were discouraged from using (disease-modifying) treatment for fear of cervical cancer, especially since uncontrolled inflammatory activity or alternative options to control it might in themselves be risk factors for cervical cancer.”
Several pharmaceutical companies funded this research through the Swedish Society for Rheumatology.