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O199. Molecular characterization of HPV16-associated squamous cell carcinomas of the oropharynx and larynx
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122
Oral abstracts / Oral Oncology Supplement 3 (2009) 56–122
Conclusion: This review has found sufficient evidence to support a global immunisation programme to help achieve a reduction in HPV-related malignant disease of the future. doi:10.1016/j.oos.2009.06.282
O198. Etiologic significance of human papilloma virus in oropharyngeal squamous cell carcinoma in relation to tobacco and alcohol F. Farshadpour a, S. Konings a, J.S. Speel b, P. Slootweg a, R. Koole a,*, J.A. Kummer a a b
University Medical Center Utrecht, Netherlands University Medical Center Maastricht, Netherlands
Introduction: Tobacco and alcohol are known risk factors for development of oropharyngeal squamous cell carcinoma (OSCC). Increasing evidence shows that Human Papilloma Virus (HPV), particularly high-risk types HPV-16 and HPV-18, are also etiologically involved in the development of OSCC. A small proportion of patients with OSCC are lifelong non-smoking and non-drinking (NSND) patients. We hypothesized a higher HPV incidence for this NSND group. Therefore a matched pair analysis was performed to compare the presence of HPV-DNA in OSCC of 13 NSND patients with 13 patients who had a history of smoking and drinking (SD). Methods: Groups were matched on sublocation of tumor, tumor stage, age at incidence (±5 years) and sex. PCR tests on HPV-DNA, FISH analysis and p16 immunostaining were performed on paraffin embedded material of these patients. Results: NSND patients had significantly higher HPV-positive tumors than SD patients (n = 11; 84.6% vs. n = 3; 23.1%; p = 0.002). Eleven HPV-positive tumors had a positive p16 immunostaining (78.6%), p16 immunostaining was not found in any HPV-negative tumors. Discussion: HPV is strongly associated with NSND patients with OSCC. Routine HPV screening and specific HPV related therapeutic options should be considered in this distinct population without other known risk factors. doi:10.1016/j.oos.2009.06.283
O199. Molecular characterization of HPV16-associated squamous cell carcinomas of the oropharynx and larynx D. Holzinger a,b, G. Halec a,b, M. Schmitt b, M. Pawlita b, F.X. Bosch a,* a Molecular Biology Laboratory, Department of Otolaryngology, Head and Neck Surgery, Heidelberg University, Germany b Division of Genome Modifications and Carcinogenesis, DKFZ, Heidelberg, Germany
Introduction: Human papillomavirus type 16 (HPV16) has been causally linked with a subset of oropharyngeal squamous cell carcinomas (OPSCC). In a further HPV16 DNA positive OPSCC subset, and in HPV16 DNA positive SCC of the larynx (LSCC), the role of HPV16 is unclear. Since HPV DNA genotyping alone is insufficient to define the role of the virus in HNSCC, we included molecular and also analysed their interactions. Methods: HPV DNA content of 208 fresh-frozen OPSCC and of 94 formalin-fixed paraffin-embedded LSCC was determined by multiplex papillomavirus genotyping (MPG). HPV16 DNA positive tumours were analysed by NASBA and hybridization for expression of E6*II and also integration-associated HPV16 mRNA. Expression of proteins p53, p16INK4a, pRb and Cyclin D1 was examined by immunohistochemistry on tissue microarrays.
Results: HPV16 DNA was detected in 48% of the OPSCC, and in 24% of the LSCC. Thirty-six percent of the DNA-positive OPSCC had a high viral load (designated HPV++), whereas nearly all DNA-positive LSCC had a low viral load (designated HPV+). From the results obtained so far, RNA expression occurs mainly in HPV++ tumours (6 of 10), whereas in the HPV+ group E6*II RNA expression is infrequent (2 of 12). Most HPV++ OPSCC showed reduced pRb, low Cyclin D1 and p53, and upregulated p16INK4a. In contrast, HPV+ OPSCC more often showed normal pRb, increased Cyclin D1 and p53, and reduced p16INK4a. In the HPV+ LSCC, only the latter pattern was seen which is typical for HPV negative tumours. Discussion: HPV+ OPSCC appear to behave as an intermediate group but are closer to HPV tumours. This questions whether HPV16 plays an active role in these tumours. In LSCC, active involvement of HPV16 appears to be rare. Possibly, HPV16 might act only transiently in these carcinomas. Further analyses will clarify the role of HPV16 in HPV+ carcinomas. doi:10.1016/j.oos.2009.06.284
O200. Prognostic value of HPV and cervical metastasis in oropharyngeal squamous cell carcinomas J.M.J.A.A. Straetmans a,*, N. Olthof a, I. Vos a, E.J.M. Speel a, J. Jong de b, B. Kremer a a b
Maastricht University Medical Centre, Netherlands Maastricht Radiation Oncology Hospital, Netherlands
Objective: In contrast to tumors originating from other sites of the head and neck area, the prognostic value of N-status appears to be controversial in oropharyngeal squamous cell carcinomas (OSCC). Here, we investigated if the presence of HPV16, involved in the carcinogenesis of a subset of OSCC, might be responsible for this observation, also taking into consideration patient treatment. In addition, we analyzed the prognostic value of HPV in OSCC. We focused particularly on analysing tumors from non-smokers to eliminate the strong influence of smoking on patient survival. Material and method: We retrospectively analyzed data of 81 patients with OSCC for survival rates (OS, DSS, DFS) related to nodal status and genomic HPV-16 integration, and corrected them for other clinical parameters. In addition, 44 tumors of non-smokers (23 OSCC, 21 other HNSCC) were analyzed for HPV status (PCR and FISH). Results: Thirty-three out of 81 OSCC were associated with HPV16 (41%). Their primary tumors were significantly smaller (p = 0.04) and were more often treated with surgery followed by radiotherapy compared with HPV-negative OSCC. The percentage of cases of cervical metastasis did not differ in the two groups. HPV presence and not nodal involvement was correlated with a favorable prognosis (p = 0.02). However, within different therapy groups, both parameters did not significantly influence prognosis. In non-smokers only OSCC were positive for HPV DNA (65%) and this group showed a significantly favorable prognosis compared with HPV-negative tumors (p = 0.0495). Conclusion: HPV-positive OSCC show a favorable prognosis in both smokers and non-smokers. Within different therapy groups however, HPV status is not associated with a favorable survival. HPV-positive OSCC appear to metastasize to cervical lymph nodes at less advanced T-stages, and are more often treated with surgery followed by radiotherapy. Because the frequency of HPV-positive OSCC is relatively high, our data suggest that HPV presence significantly reduces the prognostic value of N-status. doi:10.1016/j.oos.2009.06.285
122
Oral abstracts / Oral Oncology Supplement 3 (2009) 56–122
Conclusion: This review has found sufficient evidence to support a global immunisation programme to help achieve a reduction in HPV-related malignant disease of the future. doi:10.1016/j.oos.2009.06.282
O198. Etiologic significance of human papilloma virus in oropharyngeal squamous cell carcinoma in relation to tobacco and alcohol F. Farshadpour a, S. Konings a, J.S. Speel b, P. Slootweg a, R. Koole a,*, J.A. Kummer a a b
University Medical Center Utrecht, Netherlands University Medical Center Maastricht, Netherlands
Introduction: Tobacco and alcohol are known risk factors for development of oropharyngeal squamous cell carcinoma (OSCC). Increasing evidence shows that Human Papilloma Virus (HPV), particularly high-risk types HPV-16 and HPV-18, are also etiologically involved in the development of OSCC. A small proportion of patients with OSCC are lifelong non-smoking and non-drinking (NSND) patients. We hypothesized a higher HPV incidence for this NSND group. Therefore a matched pair analysis was performed to compare the presence of HPV-DNA in OSCC of 13 NSND patients with 13 patients who had a history of smoking and drinking (SD). Methods: Groups were matched on sublocation of tumor, tumor stage, age at incidence (±5 years) and sex. PCR tests on HPV-DNA, FISH analysis and p16 immunostaining were performed on paraffin embedded material of these patients. Results: NSND patients had significantly higher HPV-positive tumors than SD patients (n = 11; 84.6% vs. n = 3; 23.1%; p = 0.002). Eleven HPV-positive tumors had a positive p16 immunostaining (78.6%), p16 immunostaining was not found in any HPV-negative tumors. Discussion: HPV is strongly associated with NSND patients with OSCC. Routine HPV screening and specific HPV related therapeutic options should be considered in this distinct population without other known risk factors. doi:10.1016/j.oos.2009.06.283
O199. Molecular characterization of HPV16-associated squamous cell carcinomas of the oropharynx and larynx D. Holzinger a,b, G. Halec a,b, M. Schmitt b, M. Pawlita b, F.X. Bosch a,* a Molecular Biology Laboratory, Department of Otolaryngology, Head and Neck Surgery, Heidelberg University, Germany b Division of Genome Modifications and Carcinogenesis, DKFZ, Heidelberg, Germany
Introduction: Human papillomavirus type 16 (HPV16) has been causally linked with a subset of oropharyngeal squamous cell carcinomas (OPSCC). In a further HPV16 DNA positive OPSCC subset, and in HPV16 DNA positive SCC of the larynx (LSCC), the role of HPV16 is unclear. Since HPV DNA genotyping alone is insufficient to define the role of the virus in HNSCC, we included molecular and also analysed their interactions. Methods: HPV DNA content of 208 fresh-frozen OPSCC and of 94 formalin-fixed paraffin-embedded LSCC was determined by multiplex papillomavirus genotyping (MPG). HPV16 DNA positive tumours were analysed by NASBA and hybridization for expression of E6*II and also integration-associated HPV16 mRNA. Expression of proteins p53, p16INK4a, pRb and Cyclin D1 was examined by immunohistochemistry on tissue microarrays.
Results: HPV16 DNA was detected in 48% of the OPSCC, and in 24% of the LSCC. Thirty-six percent of the DNA-positive OPSCC had a high viral load (designated HPV++), whereas nearly all DNA-positive LSCC had a low viral load (designated HPV+). From the results obtained so far, RNA expression occurs mainly in HPV++ tumours (6 of 10), whereas in the HPV+ group E6*II RNA expression is infrequent (2 of 12). Most HPV++ OPSCC showed reduced pRb, low Cyclin D1 and p53, and upregulated p16INK4a. In contrast, HPV+ OPSCC more often showed normal pRb, increased Cyclin D1 and p53, and reduced p16INK4a. In the HPV+ LSCC, only the latter pattern was seen which is typical for HPV negative tumours. Discussion: HPV+ OPSCC appear to behave as an intermediate group but are closer to HPV tumours. This questions whether HPV16 plays an active role in these tumours. In LSCC, active involvement of HPV16 appears to be rare. Possibly, HPV16 might act only transiently in these carcinomas. Further analyses will clarify the role of HPV16 in HPV+ carcinomas. doi:10.1016/j.oos.2009.06.284
O200. Prognostic value of HPV and cervical metastasis in oropharyngeal squamous cell carcinomas J.M.J.A.A. Straetmans a,*, N. Olthof a, I. Vos a, E.J.M. Speel a, J. Jong de b, B. Kremer a a b
Maastricht University Medical Centre, Netherlands Maastricht Radiation Oncology Hospital, Netherlands
Objective: In contrast to tumors originating from other sites of the head and neck area, the prognostic value of N-status appears to be controversial in oropharyngeal squamous cell carcinomas (OSCC). Here, we investigated if the presence of HPV16, involved in the carcinogenesis of a subset of OSCC, might be responsible for this observation, also taking into consideration patient treatment. In addition, we analyzed the prognostic value of HPV in OSCC. We focused particularly on analysing tumors from non-smokers to eliminate the strong influence of smoking on patient survival. Material and method: We retrospectively analyzed data of 81 patients with OSCC for survival rates (OS, DSS, DFS) related to nodal status and genomic HPV-16 integration, and corrected them for other clinical parameters. In addition, 44 tumors of non-smokers (23 OSCC, 21 other HNSCC) were analyzed for HPV status (PCR and FISH). Results: Thirty-three out of 81 OSCC were associated with HPV16 (41%). Their primary tumors were significantly smaller (p = 0.04) and were more often treated with surgery followed by radiotherapy compared with HPV-negative OSCC. The percentage of cases of cervical metastasis did not differ in the two groups. HPV presence and not nodal involvement was correlated with a favorable prognosis (p = 0.02). However, within different therapy groups, both parameters did not significantly influence prognosis. In non-smokers only OSCC were positive for HPV DNA (65%) and this group showed a significantly favorable prognosis compared with HPV-negative tumors (p = 0.0495). Conclusion: HPV-positive OSCC show a favorable prognosis in both smokers and non-smokers. Within different therapy groups however, HPV status is not associated with a favorable survival. HPV-positive OSCC appear to metastasize to cervical lymph nodes at less advanced T-stages, and are more often treated with surgery followed by radiotherapy. Because the frequency of HPV-positive OSCC is relatively high, our data suggest that HPV presence significantly reduces the prognostic value of N-status. doi:10.1016/j.oos.2009.06.285