VIRAL INVOLVEMENT IN ONCOGENESIS OF OROPHARYNGEAL SQUAMOUS CELL CARCINOMA: FROM MOLECULAR MECHANISMS TO THERAPEUTIC STRATEGIES
DAN-ALEXANDRU POPESCU 1, MIRUNA-MARIA APETROAEI-LEUCĂ 1*, MIHAI-DUMITRU TUDOSIE 1,2, SIMONA-ANDREEA RUJAN 1,2, BIANCA-PETRA TAHER 1,2, RALUCA GRIGORE 1,2, ALEXANDRA MARIA MARIN 1, GLORIA-SIMONA BERTEȘTEANU 1,3, DIANA COSMINA DRĂGAN 1, BOGDAN POPESCU 1,2, IRINA DOINIȚA POPESCU 1,2, ȘERBAN VIFOR GABRIEL BERTEȘTEANU 1,²
¹ “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956, Bucharest, Romania
2 Otorhinolaryngology Department, “Colțea” Clinical Hospital, 1 Ion C. Brătianu Boulevard, 030171, Bucharest, Romania
3 Otorhinolaryngology Department, “Carol Davila” Emergency University Military Hospital, 88 Mircea Vulcănescu Street, 010825, Bucharest, Romania
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Cancer is the second leading cause of global mortality, with approximately 20% of cases attributable to infectious agents. Among the seven recognised oncogenic viruses, high-risk human papillomavirus (HPV) has driven an epidemic-like rise in oropharyngeal squamous cell carcinoma (OPSCC) across industrialised nations, even as tobacco-related disease declines. This narrative review provides an integrated, mechanistically grounded synthesis of viral involvement in oropharyngeal carcinogenesis. We discuss the molecular basis of transformation, E6- and E7-mediated inactivation of p53 and Rb within the crypt epithelium of Waldeyer's ring, through the disease's distinctive epidemiology, including the pronounced European gradient and the Romanian context, to its diagnosis, p16-based biomarker classification, and the divergent AJCC 8th edition staging. Particular emphasis is placed on therapeutic management: stage-based standards, the cautionary failure of cetuximab substitution, the rationale for de-escalation, and the emergence of immunotherapy in the curative setting. We conclude by highlighting the principal unmet needs that will shape future practice.
