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.

Keywords: head and neck neoplasms; immune checkpoint inhibitors; immunization; intensity-modulated; papillomavirus infections; radiotherapy; vaccines.

Figure 1

Schematic drawing in (A–C) illustrates the progression from normal epithelium to low-grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL), and invasive cancer, upon infection with HPV virus in cervical cancer. For oropharyngeal cancer (D), the virus is thought to infect the epithelium of the tonsillar crypt. The steps leading to invasive cancer remain unknown. Scheme created by IC. Image was created using Biorender Free Software.

Figure 2

Mechanisms of HPV infection affecting the development of OPSCC. Once HPV infects epithelium cells in the head and neck region, its DNA is integrated into the host cell genome resulting in progressive alterations in proto-oncogenes and tumor suppressor genes. The overexpression of E6 and E7 associated with protein dysregulation in the host cells leads to dysfunction in cell metabolism and malignant proliferation.