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Cervical dysplasia in immunosuppressed IBD women.

To the Editor: Cervical dysplasia (Cdys) is mainly caused by human papillomavirus (HPV) infection. It has been reported that Cdys is more prevalent among women treated with immunosuppressant drugs for some conditions such as systemic lupus erithematosus1 or renal transplantation.2 The association between inflammatory bowel disease (IBD) and Cdys has been recently suggested.3,4 However, although immunosuppressants are often prescribed in these patients, current guidelines do not recommend preventive measures or a closer screening for early Cdys detection. Within this topic, we reviewed all IBD women in whom a diagnosis of Cdys was carried out in 2 tertiary Spanish centers. A total of 7 patients were identified from our IBD databases: 3 had Crohn’s disease, 3 ulcerative colitis, and 1 indeterminate colitis. Their median age was 30 years (range 20–49), and 57% of them were current smokers. The median time from IBD and Cdys diagnosis was 24 months (range, 4–204). All of them met at least 1 criterion for disabling IBD: steroid-dependency, steroid-refractoriness, resective surgery, and/or perianal involvement. Similar to what had been previously reported in IBD patients, all our patients had received immunosuppressant drugs before the diagnosis of Cdys (7 systemic steroids, 4 azathioprine, and 1 antitumor necrosis factor). Five patients (71%) were sexually active, but none of them presented sexually transmitted diseases. Five women had a normal cervical smear prior to Cdys diagnosis. None of the cases had in situ carcinoma, 3 were CIN1, 1 CIN2, and the remaining 3 CIN3. HPV was assessed in all cervical biopsies, being positive in 5 of them. In 1 of the 2 patients with HPV-negative biopsy, HPV serology was positive. After a median follow-up of 64 months (range, 12–256), no progression to carcinoma or deaths occurred. IBD patients seem to have a higher risk of Pap smear abnormalities, and this might be even greater when evaluating inpatients,3 suggesting that an aggressive disease course may be the responsible for this difference. Drug-related immunosuppression has also been involved as a possible explanation for an increased risk of Cdys in IBD patients, but still remains a matter of debate.1,3–5 Cessation of immunosuppressants may result in the resolution of Cdys, reinforcing the statement that immunosuppression may play an important role on their pathogenesis.4 The quadrivalent HPV vaccine is indicated for the prevention of persistent infection of HPV types 16 and 18, which are associated with more than 70% of Cdys. It can be administered from 9–26 years, better prior to the initiation of sexual activity, although it can also be used in sexually active women.6 The Centers for Disease Control recommend HPV vaccination for females 11–12 years old, but it is also recommended in women with a history of HPV infection or an abnormal Pap smear.7 In Spain, the Spanish Ministry of Health is implementing the systematic HPV vaccination in prepubertal girls from this year on. Finally, some authors recommend HPV vaccination in all women with IBD on immunosuppressants, regardless of their sexual activity history.4 Nevertheless, even though promising results regarding the HPV vaccination are expected, it is yet to be evaluated on immunocompromised hosts with regard to the long-term safety profile and the real HPV protection conferred.8 Vaccination is not a substitute for routine cervical cancer screening, and vaccinated females should have cervical cancer screening as recommended. Taking into account that women with IBD may be considered at higher risk for Cdys, cervical cancer preventive measures should always be considered as part of their regular screening procedures. Strategies for Cdys prevention and surveillance could include a Pap smear prior to the beginning of immunosuppression, HPV vaccination, or more frequent cytology controls in immunosuppressed patients with an HPV-positive cervical smear.