Human Papillomavirus Oral- and Sero- Positivity in Fanconi Anemia.

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.

Oral human papillomavirus is common in individuals with Fanconi anemia.

BACKGROUND: Fanconi anemia is a rare genetic disorder resulting in a loss of function of the Fanconi anemia-related DNA repair pathway. Individuals with Fanconi anemia are predisposed to some cancers, including oropharyngeal and gynecologic cancers, with known associations with human papillomavirus (HPV) in the general population. As individuals with Fanconi anemia respond poorly to chemotherapy and radiation, prevention of cancer is critical. METHODS: To determine whether individuals with Fanconi anemia are particularly susceptible to oral HPV infection, we analyzed survey-based risk factor data and tested DNA isolated from oral rinses from 126 individuals with Fanconi anemia and 162 unaffected first-degree family members for 37 HPV types. RESULTS: Fourteen individuals (11.1%) with Fanconi anemia tested positive, significantly more (P = 0.003) than family members (2.5%). While HPV prevalence was even higher for sexually active individuals with Fanconi anemia (17.7% vs. 2.4% in family; P = 0.003), HPV positivity also tended to be higher in the sexually inactive (8.7% in Fanconi anemia vs. 2.9% in siblings). Indeed, having Fanconi anemia increased HPV positivity 4.9-fold (95% CI, 1.6-15.4) considering age and sexual experience, but did not differ by other potential risk factors. CONCLUSION: Our studies suggest that oral HPV is more common in individuals with Fanconi anemia. It will be essential to continue to explore associations between risk factors and immune dysfunction on HPV incidence and persistence over time. IMPACT: HPV vaccination should be emphasized in those with Fanconi anemia as a first step to prevent oropharyngeal cancers, although additional studies are needed to determine whether the level of protection it offers in this population is adequate.

Skin and mucosal human papillomavirus seroprevalence in persons with Fanconi Anemia.

Persons with Fanconi anemia (FA) are at risk for human papillomavirus (HPV)-associated cancers; however, their natural HPV exposure and infection rates are unknown as is the adequacy with which they mount antibodies to HPV vaccination. This study aimed to determine, in 62 persons with FA, the seroprevalence of skin and mucosal HPV types, the seroprevalence in individuals self-reporting a history of HPV vaccination, and the factors associated with HPV seropositivity. A bead Luminex assay was used to determine seropositivity for HPV1, -2, and -4 (low-risk skin), -6 and -11 (low-risk mucosal, included in one HPV vaccine), -16 and -18 (high-risk mucosal, included in both HPV vaccines), and -52 and -58 (high-risk mucosal). Health- and behavior-related questionnaires were completed. Type-specific seroprevalence estimates and participant characteristics associated with seroprevalence were calculated; 48% reported HPV vaccination. Type-specific seropositivity in unvaccinated persons ranged from 7 to 21% for skin HPV types and 7 to 38% for mucosal HPV types. Among the unvaccinated participants, adults versus children demonstrated increased HPV1, -6, -16, and -58 seroprevalence of 45% versus 6%, 64% versus 22%, 64% versus 17%, and 36% versus 0%, respectively (all P < 0.05). The vaccinated participants versus the nonvaccinated participants demonstrated increased seroprevalence of HPV6, -11, -16, and -18 of 92% versus 38%, 92% versus 24%, 96% versus 34%, and 75% versus 7%, respectively (all P < 0.0001). Our data demonstrate that the unvaccinated participants had serologic evidence of prior skin and mucosal HPV infections and that seroprevalence increased among adults; in self-reported vaccinees, seroprevalence of HPV vaccine types was 75 to 96%.