Prognostic value of p16 expression and alcohol consumption in Japanese patients with oropharyngeal squamous cell carcinoma

Abstract

BACKGROUND:The prevalence and prognostic value of human papillomavirus-related oropharyngeal squamous cell carcinoma (OPSCC) in Japan has not been evaluated. METHODS: Over a 12-year period, the authors used immunohistochemistry to evaluate the expression of p16 (a cyclin-dependent kinase inhibitor and tumor suppressor) in samples from 173 patients with OPSCC at a single institution and to determine its prevalence and influence on disease prognosis. RESULTS: The prevalence of p16-positive OPSCC was 33.7% in tonsillar carcinoma, 28.6% in tongue base carcinoma, 0% in posterior wall carcinoma, and 18.8% in soft palate carcinoma. The prevalence of p16-positive OPSCC tumors increased from 15.2% during 2000 to 2003 up to 33.3% during 2008 to 2011; during the same periods, among nonsmokers, the prevalence of p16-positive OPSCC tumors increased from 21.2% to 27.8%; and, among nondrinkers, prevalence increased from 6.1% to 25%. Multivariate analysis identified p16 expression and alcohol consumption as significant, independent prognostic markers of OPSCC. CONCLUSIONS: The current results suggest that the incidence of human papillomavirus-related OPSCC in Japan is increasing and indicate that p16 expression and alcohol consumption may be significant prognostic markers of survival for patients with OPSCC in Japan. Cancer 2013;119:2005-11. V C 2013 American Cancer Society.KEYWORDS: oropharyngeal carcinoma, head and neck squamous cell carcinoma, p16, human papillomavirus, alcohol consumption, Japan. INTRODUCTIONTobacco smoking and excessive alcohol consumption traditionally have been considered the main risk factors for head and neck squamous cell carcinoma (HNSCC). Oral and oropharyngeal squamous cell carcinoma (OPSCC) are major causes of morbidity, with an estimated annual worldwide incidence of 300,000. Evidence suggests that human papillomavirus (HPV) infection is also an independent risk factor, especially for OPSCC. [1][2][3][4][5][6] Most of the available data on HPVassociated SCC were generated in the United States and Europe. The incidence of HPV-associated malignancies, such as carcinoma of the uterine cervix, varies substantially in different regions of the world; for example, the incidence of HPVrelated cervical/uterine cancer is higher in African and Asian countries than in European countries. 7 Although eastern Asia, including Japan, is known for high epidemics of several oncogenic viral infections, such as Epstein-Barr virus and hepatitis B virus, the status of HPV-related SCC in Asia has not been elucidated.The diagnosis of HPV-related OPSCC can be made using polymerase chain reaction (PCR) analysis to detect HPV DNA 2 ; however, although this is a logical approach, it is quite challenging in clinical practice. Other diagnostic methods are HPV in situ hybridization or quantification of expression of the HPV oncoproteins E6 and E7, which has the major advantage of detecting transcriptionally active HPV. These assays, however, are cumbersome, costly, and require highly trained personnel. 8 A more feasible diagnos...

Association of impaired renal function and poor prognosis in oropharyngeal squamous cell carcinoma

“…Actually, HPV status was examined in 25 patients in 2 institutions; however, only 2 patients (8%) were found to be HPV‐positive. According to other reports, the HPV‐positive rate has been rising sharply in recent years . However, cisplatin has been and will continue to be the most important key drug for the treatment of patients with oropharyngeal SCC, despite the introduction of molecular‐targeted agents for the treatment of oropharyngeal SCC and the increase in HPV‐related oropharyngeal SCC, which has a better prognosis than HPV‐negative oropharyngeal SCC .…”

Successful detection of a minute tonsillar cancer lesion on transoral examination with narrow band imaging: A report of 2 cases

“…In the present cases, a solid tumor grew within the palatine tonsil, which was covered with normal mucosa and showed a minute mucosal defect. Recently, the incidence of HPV‐related oropharyngeal cancer has been increasing; thus, a considerable number of patients showing similar clinical features, such as a minor mucosal defect on the surface of the palatine tonsil, may exist.…”

Clinical Features of Human Papilloma Virus-Related Head and Neck Squamous Cell Carcinoma of an Unknown Primary Site

“…Cohort studies from the 1990s suggested that approximately 50% of OSCC were associated with HPV, whereas more recent studies have suggested that HPV association may account for up to 70-80% of cases in North America and Europe [11,12]. In Asia, the prevalence has been reported to be 30-50% [13,14]. Therefore, a regional difference in the prevalence of HPV-associated OSCC exists.…”

“…In our retrospective study, the exact number of patients with a primary site in the oropharynx was unknown because some occult primary sites may have been controlled without detection because of the application of postoperative radiotherapy. However, this ratio was higher than that of p16 overexpression in Asian OSCC patients (30-50%) [13,14]. A presenting feature of HPV-associated OSCC is the abrupt appearance of an enlarged cervical lymph node and small primary lesion [17,18].…”