Study Shows DMTs Associated With Higher Risk of Gynecologic Complications in Women With MS

A new large, propensity-matched analysis of more than 115,000 women with multiple sclerosis (MS) reported that those treated with disease-modifying therapies (DMTs) faced significantly elevated risks of several gynecologic complications compared with untreated women, including cervical dysplasia, cervical cancer, and human papillomavirus (HPV) positivity.¹

The findings, recently published in the Multiple Sclerosis Journal, suggest that the immunomodulatory effect of MS therapies may extend beyond infection risk to include measurable downstream effects on cervical and vulvovaginal health. Study authors, led by senior author Riley Bove, MD, an associate professor of neurology at the University of California, San Francisco, argued the results support integrating gynecologic counseling and screening into routine MS care.

When asked what neurologists should change in how they counsel women with MS starting DMTs, Bove offered the following comment to NeurologyLive^®. "In clinical practice, neurologists can implement a few changes. [First], before starting a DMT, [neurologists] would ensure the patient has been vaccinated against HPV. [Second], pre-DMT and routine clinical counseling should inform patients that they could experience gynecological symptoms and that if they do, collaboration between the gynecology and neurologist teams is warranted. [Third], for women on some immunomodulatory therapies, cervical atypia/cancer screening should occur according to guidelines for women who are immune compromised."

This retrospective cohort study drew on TriNetX, a federated network aggregating deidentified electronic health records from 105 health care organizations, most of them large US academic medical centers. Investigators identified women with an MS diagnosis between 2010 and 2025 and built two 1:1 propensity-matched cohorts of 57,761 patients each, comparing those with any DMT exposure with those who had never received a DMT. Matching balanced age, marital status, race, ethnicity, tobacco use, body mass index, HPV vaccination status, and history of gynecologic exams and screening.

“We used a large observational dataset. To confirm whether DMTs truly reduce immune surveillance against HPV, we need detailed prospective HPV testing before and after DMT start,” Bove told NeurologyLive.

After matching, the DMT-exposed group showed significantly higher risk across all 7 prespecified outcomes. These included HPV positivity (risk ratio [RR], 1.52; 95% CI, 1.35-1.72), cervical dysplasia (RR, 1.40; 95% CI, 1.31-1.49), cervical cancer (RR, 1.23; 95% CI, 1.03-1.46), cervicitis (RR, 1.25; 95% CI, 1.10-1.41), herpes simplex virus positivity (RR, 1.29; 95% CI, 1.14-1.45), vulvovaginitis (RR, 1.30; 95% CI, 1.23-1.37), and Bartholin cysts or abscesses (RR, 1.37; 95% CI, 1.07-1.76). A sensitivity analysis restricted to patients with at least 3 MS-coded visits per year replicated most associations, though vulvovaginitis and Bartholin cysts/abscesses were no longer significant.

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Subgroup analyses stratified by immunosuppressive intensity, low (glatiramer acetate, interferons, teriflunomide), moderate (natalizumab, sphingosine-1-phosphate modulators, fumarates, cladribine, alemtuzumab), and high (anti-CD20 therapies), showed that pooled moderate-to-high immunosuppression carried greater risk than low-intensity therapy across all outcomes. In addition, differences between the moderate and high tiers were generally modest except for HSV positivity and vulvovaginitis, both more common with high-intensity anti-CD20 exposure.

The findings build on a mixed prior literature. For example, a French registry study linked MS itself to elevated cervical cancer risk, while a Swedish registry study did not, and neither controlled for DMT use.² Notably, a prior smaller Australian cohort study of 248 women reported higher cervical pathology risk with high-efficacy therapies.³ Since virtually all cervical cancer arises from persistent HPV infection, and impaired viral clearance is a recognized consequence of immunosuppression, the authors proposed that chronic immunomodulation from DMTs may hinder HPV clearance and thereby raise dysplasia and malignancy risk over time.

The authors framed the absolute risks as low and the associations as not proof of a causal mechanism. Limitations included the retrospective, EHR-based design, which is vulnerable to misclassification and incomplete capture of care delivered outside contributing institutions. Additional limitations included in the potential detection or reporting bias, since clinicians may screen more assiduously in immunosuppressed patients, and the inability in TriNetX to assess DMT exposure duration, treatment switching, or MS disease duration.

Moreover, the researchers noted that screening and vaccination variables were also likely underreported in EHR data. Despite these caveats, the authors recommended that neurologists incorporate HPV vaccination counseling (through 45 years of age), safe-sex counseling, and immunocompromised-appropriate cervical cancer screening intervals into DMT management discussions, particularly for patients starting moderate- or high-efficacy agents.

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REFERENCES
1. Balshi A, Dempsey JP, Zhang-James Y, Bove R. Gynecologic complications of disease-modifying therapy in women with multiple sclerosis. Mult Scler. Published online August 13, 2026. doi:10.1177/13524585261475100
2. Pierret C, Mulliez A, Le Bihan-Benjamin C, Moisset X, Bousquet PJ, Leray E. Cancer Risk Among Patients With Multiple Sclerosis: A 10-Year Nationwide Retrospective Cohort Study. Neurology. 2024;103(9):e209885. doi:10.1212/WNL.0000000000209885
3. Bridge F, Brotherton J, Stankovich J, et al. Risk of Cervical Abnormalities for Women With Multiple Sclerosis Treated With Moderate-Efficacy and High-Efficacy Disease-Modifying Therapies. Neurology. 2024;102(4):e208059. doi:10.1212/WNL.0000000000208059