Antibody response to human papillomavirus vaccination and natural exposure in individuals with Fanconi Anemia

Abstract

Fanconi anemia (FA) is a rare genetic disorder associated with predisposition to head and neck and gynecological squamous cell cancers. In the general population, these cancers are commonly linked to human papillomavirus (HPV) infection. Antibodies to natural HPV infection and HPV vaccination were evaluated in 63 individuals with FA while considering host immune factors. Approximately 30% of reportedly unvaccinated participants were seropositive (HPV6–38%, HPV11–25%, HPV16–26%, and HPV18–26%). Seropositivity was significantly associated with having had sex regardless of age (p=0.007). Most participants showed seropositivity after HPV vaccination (HPV6–100%, HPV11–100%, HPV16–100% and HPV18–92%). Interestingly, titers for all 4 subtypes were significantly lower in the post-hematopoietic stem cell transplant (HSCT) participants compared to those who received the vaccine, but had not undergone HSCT (HPV6- p=0.030, HPV11-p=0.003, HPV16-p=0.018, HPV18-p=<0.001). It is unclear if these titers sufficiently protect from new infection since protective serologic cut offs have not yet been defined for the HPV vaccine. Individual immune functions were not associated with HPV seropositivity, however, underlying heterogeneous immune deficiency may explain higher rates of seropositivity in our younger unvaccinated participants (age 4–13 years). To better measure the efficacy of HPV vaccination in those with FA and other immune-compromised or cancer-prone disorders, future well-controlled vaccine studies are required.

Human Papillomavirus Oral- and Sero- Positivity in Fanconi Anemia

“…There were no statistically significant differences between the median time of sampling for this study and time post HPV vaccination for non-transplanted (median = 3 years; range 2–6 years) and transplanted groups (median 3 years; range 1-6 years) ( p = 0.27). Non-transplanted participants with FA had higher GMTs than the transplanted FA group regardless of vaccination status consistent with our previous findings [ 26 ] ( Table 7 ). Significant differences were observed with HPV18, 31 and 58.…”

“…Blood samples were collected using appropriate precautions by trained personnel. Fifty percent of the samples from participants with FA were collected at Cincinnati Children’s Hospital, with the remainder collected at FARF events as previously described [ 26 ]. Eighty-three percent of healthy control samples were collected at Cincinnati Children’s Hospital with the remainder collected from spouses and friends who attended FARF events with those with FA.…”

Two enemies, one fight: An update of oral cancer in patients with Fanconi anemia

“…These works support the hypothesis that the damage in the FA pathway may help the development of HPV‐associated cancers in individuals with FA. Although OSCC in patients with FA does not seem to be caused by HPV infection, patients with FA should consider vaccination to prevent HPV‐associated cancers …”

“…Although OSCC in patients with FA does not seem to be caused by HPV infection, patients with FA should consider vaccination to prevent HPV-associated cancers. 3,88,97 Patients with FA can present potentially malignant disorders, especially oral leukoplakia (Fig. 2), 98,99 defined by the World Health Organization as "a white patch or plaque that cannot be characterized, clinically, or pathologically as any other disease."…”

Risk of Human Papillomavirus Infection in Cancer-Prone Individuals: What We Know

“…Seropositivity ranged from 7 to 21% for skin HPV types and from 7 to 38% for mucosal HPV types in unvaccinated individuals with FA; in self-reported vaccine recipients, the serological positivity to HPV vaccine types was 75 to 96% [ 76 ]. Our more recently published study of the immune response in FA reported antibody responses to natural HPV infection and HPV vaccination in 39 unvaccinated and 24 vaccinated patients for HPV [ 77 ]. Similar to the earlier study, 30% of reportedly unvaccinated individuals were seropositive.…”