BackgroundThe past decade has shown a sharp incline in the human papillomavirus (HPV) infection associated oropharyngeal carcinoma cases, especially in men younger than 60 years old. Tonsils are one of the key sites, within the oropharyngeal region, which shows malignant changes due to HPV infection, and there is very limited literature to understand the specific dynamics in the tonsillar areas.ObjectiveThis critical review was undertaken to explore and unravel the bio-molecular interactions and the role of specific proteins associated with HPV infection induced tumorigenesis for the tonsils.DesignA systematic search of the literature was performed utilising keywords and MeSH terms related to HPV and tonsillar carcinoma in PubMed, Scopus, Embase, and Web of Science without restrictions on dates until July 2023. All studies that reported on molecular biomarkers or genes/genetic proteins in the context of HPV associated tonsillar carcinoma were included in the study.ResultsPreliminary searches revealed a total of 2734 studies of which 23 satisfied the final inclusion criteria and were included. More than 25 proteins and biomarkers were identified, and their role in the malignant process was extracted and compiled. This review also presents a short excerpt on each of the molecules identified to provide a better understanding of the pathogenesis.ConclusionGiven the rapidly increasing number of cases, there is an urgent need for more focused research on virally induced tonsillar cancers, to develop a better understanding, and for clarity of management and treatment.