Background. Currently licensed HPV vaccines have an established role in the primary prevention of HPV-related cancers in younger populations. Despite the remarkable impact on public health outcomes worldwide, the HPV vaccination is not recommended for older adults or those with prior HPV exposure, leaving a large portion of the population at risk for recurrent HPV-related diseases. As no vaccine has yet been approved for therapeutic use, increasing interest has been raised for the putative role of the HPV vaccination as adjuvant to the standard treatment in infected patients.
Objective. To investigate the effectiveness of adjuvant HPV vaccination for secondary prevention in patients with active HPV-related disease across different susceptible organ sites.
Design, setting, and participants. This is a trial protocol for a single-institution, multidisciplinary, randomized-controlled clinical trial. Eligible participants have a diagnosis of recurrent active HPV-related disease and will be randomized to receive or not HPV vaccination as part of their treatment. Target enrollment is 264 individuals (case-control 1:1). The primary outcome is the disease recurrence rate. Secondary outcomes include time to recurrence, disease burden, and intersurgical interval. Differences in the risk for recurrence will be evaluated using Cox proportional hazard models. Participants will be followed up for up to 36 months.
Discussion. Rediscovering the role of prophylactic HPV vaccines in the secondary prevention setting paves the way to a new era in the management of HPV-related diseases. Results from this study will provide evidence on whether incorporating adjuvant HPV vaccination into routine care can decrease disease recurrence.
Confirming the efficacy of the HPV vaccine also in the secondary prevention setting would pave the way to a new era in the management of the spectrum of HPV-related diseases.
HPV-related diseases represent a substantial health burden worldwide. Persistent HPV infection causes up to 4.5% (640,000 cases) of all new cancer cases worldwide (de Martel et al., 2017). Moreover, they tend to frequently recur either because of new HPV infections, transient reactivations of latent infections or auto-inoculation in different susceptible organ sites. Currently, there is a lack of screening and treatment guidelines for patients with noncervical HSIL disease, and health professionals need to be trained to appropriately evaluate these patients. Recurrences have been associated with decreased quality of life and significant morbidity due to disfiguring tissue removal and loss of function [Herod et al., 1996; Jones et al, 2005]. In addition, follow-up and treatment of HSIL can be anxiety provoking and expensive. Therefore, although prophylactic HPV vaccination has dramatically reduced the incidence of HPV-related diseases, there is still an unmet need to reduce the risk of recurrence of preexistent conditions in older populations.
Administering HPV vaccine shortly after the standard treatment is a simple and safe intervention with potentially extraordinary outcomes. We designed the present multidisciplinary study to shed more light on the post-expositional role of HPV vaccines. Trial findings have the potential to allow to simultaneously prevent the recurrence of HPV-related diseases across different disciplines.
Last but not least, the therapies for recurrent HPV-related diseases are costly. In 2012, Chesson et al. estimated that HPV-related disease treatments cumulatively account for nearly $8 billion in direct health care costs per year. Therefore, investing in the HPV vaccination for secondary prevention could represent a cost-effective approach in both the short and longer term, that can contribute to improvements in health outcomes at lower and more sustainable costs, while supporting universal health coverage.