Human Papillomavirus Oral- and Sero- Positivity in Fanconi Anemia

SIMPLE SUMMARY: People with Fanconi anemia (FA) are genetically susceptible to gynecological cancers and cancers of the head and neck. There are known associations between oral infection with human papillomavirus (HPV) and development of head and neck cancers. This study sought to measure how common oral HPV positivity is in a large sample of people with FA followed over 8 years, while also evaluating serum titers to ascertain natural exposure to HPV, and how well people with FA who were vaccinated responded to HPV vaccination. We found that oral HPV positivity is significantly higher in individuals with FA compared to family and unrelated controls, but that response to HPV vaccination between FA and controls is similar. Common risk factors associated with HPV in the general population did not predict oral DNA positivity in FA, unlike unrelated controls. Future mechanistic and vaccinations studies are needed to understand this phenomenon. ABSTRACT: High-risk human papillomavirus (HPV) is prevalent and known to cause 5% of all cancers worldwide. The rare, cancer prone Fanconi anemia (FA) population is characterized by a predisposition to both head and neck squamous cell carcinomas and gynecological cancers, but the role of HPV in these cancers remains unclear. Prompted by a patient-family advocacy organization, oral HPV and HPV serological studies were simultaneously undertaken. Oral DNA samples from 201 individuals with FA, 303 unaffected family members, and 107 unrelated controls were tested for 37 HPV types. Serum samples from 115 individuals with FA and 55 unrelated controls were tested for antibodies against 9 HPV types. Oral HPV prevalence was higher for individuals with FA (20%) versus their parents (13%; p = 0.07), siblings (8%, p = 0.01), and unrelated controls (6%, p ≤ 0.001). A FA diagnosis increased HPV positivity 4.84-fold (95% CI: 1.96–11.93) in adjusted models compared to unrelated controls. Common risk factors associated with HPV in the general population did not predict oral positivity in FA, unlike unrelated controls. Seropositivity and anti-HPV titers did not significantly differ in FA versus unrelated controls regardless of HPV vaccination status. We conclude that individuals with FA are uniquely susceptible to oral HPV independent of conventional risk factors.