Current Status of Human Papillomavirus-Related Head and Neck Cancer: From Viral Genome to Patient Care

Abstract

Human papillomavirus (HPV) infection identified as a definitive human carcinogen is increasingly being recognized for its role in carcinogenesis of human cancers. Up to 38%–80% of head and neck squamous cell carcinoma (HNSCC) in oropharyngeal location (OPSCC) and nearly all cervical cancers contain the HPV genome which is implicated in causing cancer through its oncoproteins E6 and E7. Given by the biologically distinct HPV-related OPSCC and a more favorable prognosis compared to HPV-negative tumors, clinical trials on de-escalation treatment strategies for these patients have been studied. It is therefore raised the questions for the patient stratification if treatment de-escalation is feasible. Moreover, understanding the crosstalk of HPV-mediated malignancy and immunity with clinical insights from the proportional response rate to immune checkpoint blockade treatments in patients with HNSCC is of importance to substantially improve the treatment efficacy. This review discusses the biology of HPV-related HNSCC as well as successful clinically findings with promising candidates in the pipeline for future directions. With the advent of various sequencing technologies, further biomolecules associated with HPV-related HNSCC progression are currently being identified to be used as potential biomarkers or targets for clinical decisions throughout the continuum of cancer care.

Factors associated with the development of second primary tumours in head and neck cancer patients

“…HPV‐related tumours have a biologically distinct behaviour compared to HPV‐negative tumours which contribute to the pathophysiology of the disease. Because of its complexity, more research focussing on this issue is needed to better understand its role in the decreased risk of SPT (Dong et al, 2021 ).…”

Implications and Emerging Therapeutic Avenues of Inflammatory Response in HPV+ Head and Neck Squamous Cell Carcinoma

“…The HPV persistent infection also requires a tolerant TME-supporting virus evasion and/or the suppression of the immunological responses [ 69 ]. The intratumor immune dynamic in HPV+ HNSCC is different from HPV-negative HNSCC [ 25 , 26 , 27 , 69 , 70 , 71 ], mainly due to the activity of viral proteins constantly stimulating the immune cell repertoire [ 72 ].…”

“…The HPV persistent infection also requires a tolerant TME-supporting virus evasion and/or the suppression of the immunological responses [ 69 ]. The intratumor immune dynamic in HPV+ HNSCC is different from HPV-negative HNSCC [ 25 , 26 , 27 , 69 , 70 , 71 ], mainly due to the activity of viral proteins constantly stimulating the immune cell repertoire [ 72 ]. HPV oncoproteins interact with the host cells leading to (i) the integration of the virus into the host genome [ 73 ]; (ii) the induction of cell proliferation and differentiation; (iii) the host-cell immortalization [ 74 ]; (iv) the inhibition of apoptosis [ 75 , 76 , 77 , 78 , 79 , 80 ]; and (v) the immune evasion [ 81 ].…”

Overview of Candida albicans and Human Papillomavirus (HPV) Infection Agents and their Biomolecular Mechanisms in Promoting Oral Cancer in Pediatric Patients

“…HPVs are members of the Papillomaviridae (PV) family, presenting a circular, with supercoiled and double-stranded DNA, and some are considered as oncogenic promoters [ 64 – 66 ]. The virus has a hexahedral symmetry capsid (consisting of pentameric capsomeres) and has two structural proteins, L1 and L2 [ 67 , 68 ].…”