Therapeutic Vaccines for HPV-Associated Oropharyngeal and Cervical Cancer: The Next De-Intensification Strategy?

Abstract

The rise in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has prompted a quest for further understanding of the role of high-risk HPV in tumor initiation and progression. Patients with HPV-positive OPSCC (HPV+ OPSCC) have better prognoses than their HPV-negative counterparts; however, current therapeutic strategies for HPV+ OPSCC are overly aggressive and leave patients with life-long sequalae and poor quality of life. This highlights a need for customized treatment. Several clinical trials of treatment de-intensification to reduce acute and late toxicity without compromising efficacy have been conducted. This article reviews the differences and similarities in the pathogenesis and progression of HPV-related OPSCC compared to cervical cancer, with emphasis on the role of prophylactic and therapeutic vaccines as a potential de-intensification treatment strategy. Overall, the future development of novel and effective therapeutic agents for HPV-associated head and neck tumors promises to meet the challenges posed by this growing epidemic.

Reappraisal of p16 for Determining HPV Status of Head and Neck Carcinomas Arising in HPV Hotspots

“…The discussion remains highly relevant as the importance of HPV status has broadened beyond its traditional role as a mere prognostic marker. For example, HPV status can discern which patients may benefit from de-escalated therapy or a therapeutic HPV vaccine; 7,19,20 and it can identify those patients who may benefit from a novel surveillance approach targeting circulating plasma tumor HPV DNA testing. [21][22][23][24] Inaccurate determination could have profound clinical implications.…”

HPV vaccination for prevention of head and neck cancer among men

“…Some therapeutic vaccines for cancer treatment are in phase I of clinical studies, but none have been shown to reverse HPV-associated cancers; prevention therefore remains critical. 11,21 Although the feminization of HPV-associated cancers has had a signifi cant impact on perception of HPV risk and the importance of vaccination in prevention for males, providing appropriate recommendations and education regarding the benefi ts of vaccination can reverse misconceptions. Th rough awareness-raising efforts and patient education, NPs can improve…”

“…In the US, 71% of all individuals diagnosed with HNC were estimated to be males 16,19-21. The disproportionately higher rate in males may be explained by their lower amount of estrogen, possible variation in immune responses against HPV, and higher number of sexual partners 3,11. Research also shows that White individuals and those of high socioeconomic status have a higher prevalence of HPV-positive HNC in the US 22,23…”

“…[2][3][4][5][6] HPV serotypes 16 and 18 are associated with 85% of HPVrelated HNC; oropharyngeal cancer is the most common subset, with 62.9% of all cases of oropharyngeal cancer being HPV-positive. 1,[7][8][9][10][11][12] In many Western countries, HPV-associated oropharyngeal cancer incidence has increased by up to 225% within the last 3 decades, exceeding cervical cancer as the most prevalent HPV-linked cancer. 6,[13][14][15] Currently, the reason for the drastic increase in incidence of HPVassociated HNC is unknown, although it is hypothesized that it is the result of increasing prevalence of cancer-causing HPV strains.…”

“…16,[19][20][21] Th e disproportionately higher rate in males may be explained by their lower amount of estrogen, possible variation in immune responses against HPV, and higher number of sexual partners. 3,11 Research also shows that White individuals and those of high socioeconomic status have a higher prevalence of HPV-positive HNC in the US. 22,23 Indications for the HPV vaccine have been expanded to include the prevention of HPV-associated HNC, and national immunization programs across 47 countries include boys in their HPV vaccine recommendations.…”