BACKGROUND: Human papilloma virus (HPV) is an important risk factor for head and neck cancer, specifically oropharyngeal cancer, but its association with oral tongue squamous cell carcinoma (SCC) is uncertain. The objectives were to determine the HPV16 prevalence in oral tongue SCCs, its integration status and to correlate the expression of oncogenic proteins with targets. METHODS: In this case-control study with oral tongue SCC cases (n=60) and normal oral mucosa (n=46), HPV positivity was determined by polymerase chain reaction (PCR) using consensus and HPV 16 type specific primers and p16 immunohistochemistry (IHC). The viral integration status was determined with primers specific to the E2 gene and in situ hybridization (ISH). Immunohistochemical analysis of HPV oncogenic proteins (E6, E7) and their target proteins (p53, pRb, cyclinD1, p16, Notch-1, EGFR) proteins was carried out in HPV positive cases. The data was analyzed with SPSS software (v 11.0). Survival analysis was carried out by the Kaplan-Meier method. RESULTS: HPV16 was detected in 48% (n=29) of the cases and none of the controls by PCR assay (p<0.001) while p16 IHC, as a surrogate HPV marker, detected 33% (n=18) of the cases; 18% (n=10) were detected by both the methods. Integration was observed in 83% (n=24) by E2-PCR and 67% (n=18) by ISH. The E6-p53 pathway was active in 33% of the cases; E7-pRb in 52% and both in 11%. HPV positivity was associated with well-differentiated cancers (p=0.041) and low recurrence rate (p=0.014). CONCLUSION: Our study confirms a positive correlation of HPV infection with oral tongue cancer.
BACKGROUND:Human papilloma virus (HPV) is an important risk factor for head and neck cancer, specifically oropharyngeal cancer, but its association with oral tongue squamous cell carcinoma (SCC) is uncertain. The objectives were to determine the HPV16 prevalence in oral tongue SCCs, its integration status and to correlate the expression of oncogenic proteins with targets. METHODS: In this case-control study with oral tongue SCC cases (n=60) and normal oral mucosa (n=46), HPV positivity was determined by polymerase chain reaction (PCR) using consensus and HPV 16 type specific primers and p16 immunohistochemistry (IHC). The viral integration status was determined with primers specific to the E2 gene and in situ hybridization (ISH). Immunohistochemical analysis of HPV oncogenic proteins (E6, E7) and their target proteins (p53, pRb, cyclinD1, p16, Notch-1, EGFR) proteins was carried out in HPV positive cases. The data was analyzed with SPSS software (v 11.0). Survival analysis was carried out by the Kaplan-Meier method. RESULTS:HPV16 was detected in 48% (n=29) of the cases and none of the controls by PCR assay (p<0.001) while p16 IHC, as a surrogate HPV marker, detected 33% (n=18) of the cases; 18% (n=10) were detected by both the methods. Integration was observed in 83% (n=24) by E2-PCR and 67% (n=18) by ISH. The E6-p53 pathway was active in 33% of the cases; E7-pRb in 52% and both in 11%. HPV positivity was associated with well-differentiated cancers (p=0.041) and low recurrence rate (p=0.014). CONCLUSION: Our study confirms a positive correlation of HPV infection with oral tongue cancer.
Authors: Huaising C Ko; Paul M Harari; Ryan M Sacotte; Shuai Chen; Aaron M Wieland; Menggang Yu; Andrew M Baschnagel; Justine Y Bruce; Randall J Kimple; Matthew E Witek Journal: J Cancer Res Clin Oncol Date: 2017-07-27 Impact factor: 4.553