MOUTH CANCER AND
THE HUMAN PAPILLOMA VIRUS
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Human papillomavirus: its identity and controversial role in oral oncogenesis, premalignant and malignant lesionsInt J Oncol. 2007 Apr;30(4):813-23.Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with a remarkable epithelial cell specificity: they have been reported principally in the ano-genital tract, urethra, skin, larynx, tracheo-bronchial and oral mucosa. More than 100 different HPV types have been identified and classified as high (e.g. 16, 18, 31) or low (e.g. 11, 42, 36) -risk (HR and LR), based on their association with cervical carcinoma. The carcinogenic role of HR-HPV revolves mainly around two of its oncoproteins: HPV-E6 which promotes degradation of the p53 tumour suppressor gene product and HPV-E7 which modifies the pRb tumour suppressor gene product, inhibiting the activity of TGF-beta2. Since these viral oncoproteins are capable of transforming primary human keratinocytes from either genital or upper respiratory tract epithelia, they have been considered to play a role in disrupting cell-cycle regulatory pathways leading to a genetic progression to ano-genital cancer and, possibly, also to oral squamous cell carcinoma (OSCC). Recently, the oncogene HPV-E5 has also been found to transform cells by modulating growth factor receptors. On the basis of the high, although very variable, frequency of HR-HPV in OSCC, an oral malignant potential of HPV infection has been hypothesised but not definitively confirmed.Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx.Int J Cancer. 2003 Apr 10;104(3):336-44./Although studies have established human papillomaviruses (HPVs) as a risk factor for oral and oropharyngeal cancer, it is not clear whether viral infection affects survival in head and neck malignancies. This investigation examined the relationship between HPV and survival in carcinomas of the oral cavity and oropharynx. Formalin-fixed, paraffin-embedded tumor specimens from 139 newly diagnosed cases were tested for HPVs by PCR and DNA sequencing. Patient and tumor characteristics were obtained from questionnaires, pathology reports and cancer registries. Odds ratios (ORs) and relative risks (RRs) were based on logistic and Cox regression models, respectively. HPVs were detected in 21% of the tumors; 83% were HPV-16. Greater risk of HPV infection was associated with males (OR = 2.9), a history of oral-genital sex (OR = 4.2), and oropharyngeal tumors (OR = 10.4). As tobacco usage increased, the odds of HPV detection decreased (OR = 0.97/pack-year). HPV infected patients had better overall survival (RR = 0.3) than those with HPV-negative tumors. There was an interaction between gender and HPV for overall (p = 0.05) and disease-specific (p = 0.03) survival that suggested that HPV infected males had better prognosis than HPV-negative males, but this was not the case among females. HPV status was identified as an independent prognostic factor in oral and oropharyngeal cancers. This result appeared to be gender-specific, suggesting the need for further study of the interaction between HPV and gender on survival.Human papillomavirus-16 in oral squamous cell carcinoma: clinical correlates and 5-year survival.Br J Oral Maxillofac Surg. 2007 Mar;45(2):116-22. Epub 2006 Jun 15. We examined 66 oral squamous cell carcinomas (OSCCs) for human papillomavirus-16 (HPV-16) infection to evaluate its prognostic significance. Cox regression analysis of 5-year survival demonstrated that patients without nodal metastasis or with intratumoural HPV-16 showed better prognoses compared with each counterpart. In Kaplan-Meier survival analysis, nodal status but not HPV-16 status was statistically significant. The 5-year survival rate of HPV-16 positive patients without nodal metastasis (94%) was extremely high, compared with that of HPV-16 negative patients with nodal metastasis (25%). These results suggest that HPV-16 status as well as nodal status may provide prognostic significance in patients with OSCC. |