HPV-associated oropharyngeal cancer: in search of surrogate biomarkers for early lesions

Abstract

The incidence of oropharyngeal cancer (OPSCC) has escalated in the past few decades; this has largely been triggered by high-risk human papillomavirus (HPV). Early cancer screening is needed for timely clinical intervention and may reduce mortality and morbidity, but the lack of knowledge about premalignant lesions for OPSCC poses a significant challenge to early detection. Biomarkers that identify individuals at high risk for OPSCC may act as surrogate markers for precancer but these are limited as only a few studies decipher the multistep progression from HPV infection to OPSCC development. Here, we summarize the current literature describing the multistep progression from oral HPV infection, persistence, and tumor development in the oropharynx. We also examine key challenges that hinder the identification of premalignant lesions in the oropharynx and discuss potential biomarkers for oropharyngeal precancer. Finally, we evaluate novel strategies to improve investigations of the biological process that drives oral HPV persistence and OPSCC, highlighting new developments in the establishment of a genetic progression model for HPV + OPSCC and in vivo models that mimic HPV + OPSCC pathogenesis.

Analogies between HPV Behavior in Oral and Vaginal Cavity: Narrative Review on the Current Evidence in the Literature

“…Indeed, the implementation of national screening programs, complemented by the introduction of the anti-HPV vaccine, has succeeded in lowering HPV morbidity and cervical cancer mortality by 70% (7.4 per 100,000) in industrialized countries [ 13 ]. In contrast to cervical cancer, the natural history of HPV infection in the oropharynx remains inadequately understood [ 14 ].…”

Moderate SCRIB Expression Levels Correlate with Worse Prognosis in OPSCC Patients Regardless of HPV Status

“…Up to 96% of these tumors are HPV16-positive (HPV16+) and, in contrast to cervical cancer, precancerous lesions are hardly detected [ 6 ]. HPV+ HNSCCs seem to differ from HPV-negative (HPV−) ones in genetic, epigenetic, and protein expression profiles, as well as epidemiological factors and clinical characteristics [ 7 , 8 , 9 , 10 ], but the currently available treatments for both groups are almost the same [ 7 , 11 , 12 ]. Similar to cervical infections, the majority of head and neck HPV infections (as high as 80%) are cleared by the immune system in healthy individuals within 6 to 20 months of the initial infection [ 3 , 13 ].…”

“…HR HPVs are associated with nearly 100% of cervical cancer cases, of which, the most notable are HPV16 and HPV18, which alone are responsible for approximately 70% of those cases. On the other hand, oropharyngeal cancers are primarily caused by HPV16 and show low or sporadic association with HPV18 or other HR HPV types [ 9 , 19 , 25 ].…”

Changing the paradigm: Elimination – Not only of cervical cancer

“…There are currently no screening methods and guidelines in place for the early detection of OPC, since the current technologies are inadequate for diagnosing precancer and early OPC and serum biomarkers are still under investigation ( Lim and D'Silva, 2024 ).…”