Effect of Anti-Psoriatic Biologics on Risk of Anogenital Warts (CONDYPSO)

Scientific Rationale

Anogenital warts (AGW) are a frequent manifestation of human papillomavirus (HPV) infection. Their course is generally benign, but they may cause significant discomfort and carry a high risk of recurrence, particularly in the context of immunomodulation.

Psoriasis is a chronic inflammatory skin disease affecting approximately 2-3% of the global population. Biologic therapies targeting IL-17 and IL-23, now widely used, profoundly modulate mucosal immunity by acting on the Th17 axis. This pathway plays a central role in defense against viral and fungal pathogens on mucosal surfaces, notably through the production of IL-17 and IL-22. Their inhibition leads to a decrease in these cytokines, which could theoretically impair local viral clearance, particularly with respect to HPV, thereby promoting persistence or recurrence of AGW.

Anti-TNF-α agents, long used in dermatology, also influence antiviral immunity by reducing the activity of cytotoxic CD8+ T lymphocytes and the production of IFN-γ, a key Th1 cytokine.

This rationale is supported by experimental data showing the essential role of Th1 and Th17 pathways, CD8+ lymphocytes, dendritic cells, and IFN-γ in the control of HPV infections.

A cross-sectional study in 222 patients with psoriasis or inflammatory bowel disease, including 104 treated with anti-TNF-α, did not demonstrate a significant increase in the prevalence of anogenital HPV infections compared with patients receiving alternative therapies or no treatment. At baseline, the analysis combined grouped anogenital swabs (penis or vulva, perianal area, and cervix in women) with broad-spectrum HPV PCR, together with serology for neutralizing antibodies against genotypes 6, 16, and 18. However, this study does not allow conclusions on the long-term safety of these treatments, nor on the risk associated with individual molecules, due to sample size and the cross-sectional design.

Another, more recent cross-sectional study suggested an increased prevalence of oral HPV infections in psoriatic patients treated for at least 6 months with anti-IL-17, particularly after prolonged exposure (\>8 years), compared with patients receiving topical treatments or other biologics (anti-TNF-α or ustekinumab). HPV PCR on oral rinse was performed at a single time point at inclusion. Genital infections were also investigated using perineal swabs with PCR analysis, but results were less conclusive, with no statistically significant differences between groups.

Several case reports have described the occurrence or worsening of AGW in patients receiving anti-IL-17 or anti-TNF-α, suggesting a possible negative impact on viral clearance. These remain isolated observations and do not establish causality.

Conversely, elevated levels of interleukins 17 and 23 have been detected in HPV-induced lesions, particularly in the cervix and anal canal. Their inhibition might therefore exert a protective effect against the progression of HPV-induced lesions.

Cases of regression of warts, including AGW and cutaneous warts, have indeed been reported under anti-IL-17, as well as a case of regression of high-grade HPV-associated dysplasia after switching from an anti-IL-12/23 (ustekinumab) to a selective anti-IL-23 (risankizumab). To date, no cases of AGW have been reported with the newer anti-IL-23 agents such as guselkumab, risankizumab, or tildrakizumab, while a single isolated case under ustekinumab was published in 2021.

A review of the literature confirms the lack of robust quantitative data in patients treated with IL-17 and IL-23 inhibitors and highlights the scarcity of studies focusing on anogenital sites.

In addition, the use of topical corticosteroids or calcineurin inhibitors in the anogenital area may locally reduce mucosal immunity and contribute to persistent or recurrent HPV infection.

The role of biologics targeting TNF-α, IL-17, and IL-23 in the course of HPV infections therefore remains uncertain, complex, and likely dependent on immunological mechanisms that are still not fully understood. These considerations justify systematic studies to assess their specific impact on the incidence and recurrence of anogenital warts in psoriatic patients.

Finally, very limited data are available regarding risk perception of HPV infection and acceptability of HPV vaccination in this adult population receiving immunomodulatory treatments, despite the fact that prevention could be relevant.

Study Design

Type: Mixed study (retrospective + prospective) Total duration: 30 months (2026-2028) Retrospective phase: 3 months (Feb-Apr 2026) Prospective phase: 30 months (Feb 2026 - Aug 2028) Analysis phase: after completion of follow-up

The retrospective phase will consist of a case-control study, matching each patient who developed anogenital warts (AGW) with one or more controls receiving biologic therapy who did not develop AGW, in order to identify factors associated with their occurrence and to more precisely estimate the relative risk of AGW under biologic therapies, beyond simple case description.

Enrollment period (prospective phase): Patients will be enrolled starting in February 2026. Each patient will be followed for 24 months after enrollment, during their routine dermatology visits for psoriasis management. No additional visits will be required by the study. Relevant data will be collected during routine consultations. All data will be available prior to the start of the analysis phase.

An anonymous questionnaire on HPV vaccination acceptability will be offered during the prospective phase only to enrolled participants without a known history or current clinical lesion of condyloma, HSIL, or HPV-induced carcinoma, regardless of vaccination status, whether or not they are receiving systemic immunomodulatory therapy (anti-TNF-α, anti-IL-17, anti-IL-23, methotrexate, cyclosporine, deucravacitinib, dimethyl fumarate). The purpose of this approach is not to promote vaccination, but to collect data on HPV risk perception and willingness to be vaccinated, while enabling a comparative analysis between treated and untreated patients. The acceptability rate will be defined as the proportion of patients who state they would accept vaccination if it were offered.

These timelines are indicative and may be adjusted depending on the actual number of inclusions or potential delays related to ethical or logistical processes.

To ensure sufficient homogeneity in the prospective phase, both in terms of diagnosis and management, precise clinical definitions as well as a therapeutic reference document will be provided to investigators:

Anogenital wart (AGW): papillomatous lesion suggestive of HPV infection, clinically diagnosed by a dermatologist; histological confirmation may be performed in atypical or doubtful cases.

Recurrence: reappearance of lesions clinically compatible with AGW, after documented complete resolution of the initial episode.

Management of AGW will be based on French recommendations from the Haute Autorité de Santé (HAS), adapted to the Belgian therapeutic context. In particular, podophyllotoxin, recommended as first-line therapy in France, is currently unavailable in Belgium. It will therefore be replaced in the reference grid by Veregen®, which is widely used in local practice.

This adaptation is intended to guarantee a minimum level of treatment homogeneity while respecting local prescribing realities. The adapted grid will be communicated to investigators involved in the prospective phase, in order to ensure harmonization of AGW management practices during the study.

Data Collected

Common data (retrospective + prospective):

Sex, age, phototype, BMI

Type and duration of psoriasis (plaque, guttate, pustular), mode of diagnosis (clinical/histological)

Disease severity (BSA, PASI)

HPV vaccination status (vaccine, dates, and number of doses)

Current and past treatments (antipsoriatic and others, continuous or not)

Genital involvement of psoriasis: yes/no

Topical use in the genital area: molecule, duration, frequency

Comorbidities (notably HIV, diabetes, immunosuppression, chronic inflammatory diseases, etc.)

Gynecological-obstetrical status (for female patients): current pregnancy, recent pregnancy (\<12 months), breastfeeding

Sexual history (relationship status, gender of sexual partners, multiple partners, unprotected intercourse, PrEP use, chemsex practices)

Addictive behaviors (smoking, drug use, alcohol)

History of STIs and anogenital warts (clinical/histological diagnosis, localization, number of lesions, dates, treatment)

History of HSIL or invasive carcinoma (cervical, anal, vulvar, vaginal, penile,

• Characterization of AW cases under biologics [Срок оценки: From enrollment until the end of the 2-year follow-up]
• Comparison of incidence and recurrence across treatments [Срок оценки: From enrollment until the end of the 2-year follow-up]
• Risk factors for AW incidence and recurrence [Срок оценки: From enrollment until the end of the 2-year follow-up]
• Impact of topical genital therapies [Срок оценки: From enrollment until the end of the 2-year follow-up]
• HPV vaccination acceptability [Срок оценки: At enrollment]
• HPV genotyping in prospective cases [Срок оценки: After completion of the 2-year follow-up of enrolled patients]