Probes for HPV

The favorable features of high-risk human papillomavirus (HPV) in the head and neck are limited to those harboring transcriptionally-active HPV, which occur predominantly in the oropharynx (OP). Factors rendering the OP susceptible to HPV oncogenesis are largely unexplored. The role of cytokeratin 7 (CK7) in predisposition to HPV and cancer in the cervix has been evaluated. However, its significance in the H&N is unknown. CK7 immunohistochemistry was performed on a tissue microarray cohort of OP and non-oropharyngeal (NOP) squamous cell carcinomas (SCC) with known clinical follow-up and HPV E6/7 mRNA status. Expression was graded based on the distribution (1 ≤ 33%, 2 = 33-66%, 3 ≥ 66%) and intensity (1 = weak, 2 = strong) with combined score of ≥ 2 considered positive. Survival analysis was performed. Seventy-four NOPSCCs and 204 OPSCCs were studied. HPV was positive in 2.7% of NOPSCCs and 70.9% of OPSCCs. CK7 was positive in 23.0% of OPSCCs and 14.8% of NOPSCCs (p = 0.2), and in 24.1% of HPV positive versus 17.2% of negative patients (p = 0.2). There was no correlation with age, race, gender, HPV status, histologic type, tumor subsite, treatment, stage, or co-morbidities, and CK7 expression was not significantly associated with overall or disease specific survival. In our series, CK7 is positive in ~ 25% of H&N SCCs, although usually only focally. While CK7 has been suspected to be overexpressed selectively in HPV-related OPSCCs due to their origination from tonsillar crypt epithelium, we did not find any significant difference by anatomic H&N subsite, nor by HPV status, for its expression and found no association with patient survival.

Primary carcinomas of the urethra are rare and poorly understood lesions, hence their clinical and pathologic spectrum is not completely defined. We analyzed a series of 130 primary urethral tumors and classified 106 of them as primary urethral carcinomas. The age at diagnosis of patients with primary urethral carcinomas ranged from 42-97years (mean: 69.4yrs.; median: 70yrs). There were 73 males and 33 female patients with a ratio of 2.2:1. In male patients the tumors most frequently developed in the bulbous-membranous segment of the urethra. In female patients the entire length of the urethra was typically involved. Microscopically, they were poorly differentiated carcinoma with hybrid squamous and urothelial features and developed from precursor intraepithelial conditions such as dysplasia and carcinoma in situ, which were frequently present in the adjacent urethral mucosa. High risk HPV infection could be documented in 31.6% of these tumors. Follow-up information was available for 95 patients. Twenty-three patients died of the disease with a mean and median survival of 39 and 21months respectively. Urethral carcinomas are aggressive tumors with high propensity for regional and distant metastases with mean and median survival of 39 and 21months respectively. Our observations have important implications for the management of patients with primary carcinoma of the urethra by defining them as a unique entity linked to HPV infection.