Knowledge About Human Papillomavirus Among Patients With Immune-Mediated Inflammatory Diseases

To the Editor:

Patients with immune-mediated inflammatory diseases (IMIDs) exposed to immunosuppressive therapy are at increased risk of persistent human papillomavirus (HPV) infection.^1,2 Persistent HPV infection can cause cervical cancer, but also cancers of the vulva, vagina, penis, anus, and oropharynx.³ HPV vaccination is safe and has demonstrated preventive benefits on cervical cancer and incidence of grade 3 cervical intraepithelial neoplasia in young women.⁴ Despite the recommendation by the European Alliance of Associations for Rheumatology (EULAR),⁵ HPV vaccination coverage remains worryingly low in patients with IMIDs.^6,7 We wanted to assess what patients with IMID know about HPV infection.

We conducted the PAPILLOVAX study, which consisted of an online questionnaire designed using anonymous SurveyMonkey responses for data recording and processing. The study targeted patients with a self-reported diagnosis of IMIDs. The study addressed epidemiological features, HPV vaccine uptake, and knowledge about HPV infection. The survey took place from April 1 to June 30, 2024, and was distributed to patients attending medical appointments or via mailing lists from 2 tertiary university centers in Paris and Lille, France. Distribution was facilitated by the French Rare Autoimmune and Autoinflammatory Diseases Health Network (FAI2R) and the main French associations of patients with IMID. Surveys filled partially (< 60% of answers completed) or by patients who did not report a diagnosis of IMID were excluded from the analysis.

Main study outcomes included a self-reported medically confirmed diagnosis of IMID, history of vaccination against HPV, intention to get vaccinated when vaccine is available (ie, catch-up vaccination), and self-reported knowledge about HPV infection. The questionnaire consisted of 12 statements, with each participant responding to these items by choosing true or false. A correct response to an item was assigned 1 point, whereas an incorrect response was assigned 0 points. The maximum total score ranged from 0 to 12. The comparison of knowledge scores between patients with vs without vaccine willingness was assessed using Wilcoxon signed-rank test. Age, gender, type of IMID, and knowledge score were considered in a multivariable logistic regression model to identify those independently associated with vaccine willingness, with estimation of odds ratios (ORs) and 95% CIs. Statistical analysis was performed using R software (Version 1.6.15; R Core Team).

Four hundred twenty-nine patients participated in the study. Surveys partially completed (n = 34) or completed by patients not reporting IMIDs (n = 18) were excluded, and 377 questionnaires were analyzed. Most of the patients (80.9%, n = 305/377) were aged between 20 and 65 years, and 85.4% (n = 322/377) were women. Systemic lupus erythematosus, Sjögren disease, systemic vasculitis, inflammatory myositis, and systemic sclerosis accounted for 77.2% (n = 291/377) of the reported IMIDs. Patient characteristics are given in Table 1.

More than 20% (n = 85/377) of patients did not know that cervical cancer is caused by HPV and approximately 60% (n = 229/377) did not know that HPV can cause throat cancer (Table 2). Two-hundred five patients (54.4%) were unaware that HPV infection is more common in patients undergoing immunosuppressive therapy. Approximately 35% (n = 134/377) of patients ignored that HPV is transmitted during sexual intercourse. Around 25% (n = 100/377) were unaware of the existence of an effective vaccine against HPV. Approximately 10% of patients (n = 34/377) falsely believed that IMIDs contraindicated HPV vaccination, and around 32% (n = 121/377) did not know that HPV vaccination might be proposed in adulthood as a catch-up vaccination. Overall, the mean knowledge score about HPV was 8.0 ± 3.3 (range 0-12; Table 2).

Only 35 patients of 377 (9.3%) reported routine HPV vaccination during teenage years that was performed prior to the diagnosis of IMID (Table 1). More than 80% of the vaccinated patients (n = 29/35) were under the age of 40 at the time of survey, in line with the first introduction of HPV vaccination in France in 2007.⁸ Of note, almost 50% of patients (n = 157/318) would accept a catch-up vaccination in adulthood. Interestingly, vaccination willingness was associated with a higher score of knowledge about HPV (mean score of 8.9 ± 2.1 in those who would accept [n = 157] as compared to 7.5 ± 3.5 in those who would decline vaccination [n = 161; P < 0.01]). The association between vaccination willingness and knowledge were still significant through multivariable logistic regression analysis involving gender, age, and type of IMID (OR 1.22, 95% CI 1.11-1.34 for an increment of 1 point).

Our survey shows that knowledge about HPV infection is limited in patients with IMID but suggests that improving the education of patients on this topic might improve HPV vaccination coverage.

Our study has several limitations. Patients without internet access or those less comfortable with such technology might be underrepresented, introducing potential bias. The knowledge assessment is based on 12 true or false statements, which may oversimplify the complexity of understanding HPV and its related risks. Although HPV vaccine is recommended for routine vaccination at age 11 or 12 years before the start of sexual activity,⁸ we included a very limited number of patients with IMID younger than 20 years.

The dramatically low frequency of HPV vaccination in IMIDs highlights the urgent need for increased awareness among rheumatologists regarding HPV-related diseases. A proactive approach, including targeted campaigns and the systematic integration of vaccination into patient care, is essential to protect this vulnerable population.

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