The role of oncogenic human papillomaviruses in tonsillar squamous cell carcinomas with functional inactivation of the retinoblastoma protein

In order to identify squamous cell carcinomas of the head and neck (HNSCC) with common biological and clinical features, we investigated the incidence and properties of carcinomas lacking retinoblastoma protein (pR6) cell cyc le control. Of 208 HNSCC investigated, 23 (11%) showed a lack of pRb expres sion. The majority of these tumors (65%) were tonsillar carcinomas. The pRb -negative tonsillar tumors were all stage IV, had metastasized to lymph nod es at the time of diagnosis and were in general poorly differentiated or un differentiated. Very significantly, the pRb-negative phenotype was strongly associated with the presence of oncogenic human papilloma viruses, implyin g a viral etiology and functional inactivation of pRb by the viral E7 oncop rotein. Despite the very adverse histopathological factors, patients with p Rb-negative tonsillar carcinomas had a better clinical outcome, which was c onsistent with a uniform favorable responsiveness of these tumors to postop erative radiation therapy.