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O83 No relationship between HPV and Oral Squamous Cell Carcinoma (OSCC) in patients who do not use tobacco and alcohol
84 18/27 patients and 17/18 of surviving patients have had a preservation of the (pharyngo)larynx. The most common toxicities were nausea and vomiting and mucositis. Conclusion: Organ preservation, with multimodality treatment, may be achievable in some of the patients with respectable, advanced upper aerodigestive tract cancers without compromise the survival. Keywords: induction chemotherapy, advanced cancer, chemoradiotherapy, neck dissection O83 No relationship between HPV and Oral Squamous Cell Carcinoma (OSCC) in patients who do not use tobacco and alcohol T.J.H. Siebers *, M.A.W. Merkx, P.J. Slootweg, W.J.G. Melchers, P. van Cleef, P.C.M. de Wilde. Radboud University Nijmegen Medical Centre, Netherlands Introduction: The relationship between human papillomavirus (HPV) and SCC is well documented, particularly in the oropharynx. This HPV expression seems to depend on the anatomical location of the primary tumor. Regarding the oral cavity, the presence of HPV genome has been reported with various percentages and genotyping patterns. However, it has been suggested that only a minority of the OSCC is associated with oncogenic HPV-16, -18, -31, and -33. The controversy in the literature about the various percentages of HPV in OSCC’s may be due to different detection methods and their sensitivity. The aim of this study was to evaluate the role of HPV in 7 consecutive non-smoking and non-drinking patients (2004 2005) with an OSCC located at the tongue. Materials and Methods: Histological paraffin embedded specimen were tested for the detection and genotyping of HPV16, -18, -31, and -33. Both ISH and HPV SPF10 Line Blot 25 PCR, assays were used [1,2]. Results: In none of the patients with OSCC of the tongue HPV16, -18, -31, -33 was found using ISH and PCR. Conclusion: With ISH as well as PCR, no HPV was detected in OSCC of the tongue, in non-drinking and non-smoking patients. Because of these results it is questionable whether HPV plays a role in the development of OSCC. Keywords: OSCC, HPV Reference(s) [1] Melchers WJ, Bakkers JM, Wang J, de Wilde PC, Boonstra H, Quint WG, Hanselaar AG. Short fragment polymerase chain reaction reverse hybridization line probe assay to detect and genotype a broad spectrum of human papillomavirus types. Clinical evaluation and follow-up. Am J Pathol. 1999;155(5):1473 8. [2] Li G, Sturgis EM. The role of human papillomavirus in squamous carcinoma of the head. Curr Oncol Rep. 2006;8(2):130 9. O84 Follow-up and management of oropharyngeal and laryngeal dysplasia: a 10-year case series J. Smith *, T. Rattay, H. Mehanna, M. Iles. University Hospital Coventry and Warwickshire NHS Trust, United Kingdom Objectives: To identify the current follow-up and management of oropharyngeal and laryngeal dysplasia. To compare this practice with an evidence-based follow-up protocol. Design: Retrospective case series of oral and laryngeal dysplasias attending University Hospitals Coventry and Warwickshire. Selection criteria: Included: new histological diagnoses of oropharyngeal or laryngeal dysplasia: 1994 and 2005. Excluded: previous or simultaneous SCC. Outcome measures: Risk factors, success of risk factor intervention. Grade of dysplasia and change in grade. Duration and interval of follow-up. Progression to cancer. Treatment.
Oral and Symposium abstracts, Saturday 19 May Data collection and Analysis: Identification through histology records. Notes were analysed and outcome measures recorded. Results: Of 149 cases, 31 were excluded and 4 lost to follow-up. 79 patients had dysplasia of the larynx; 35 had oropharyngeal dysplasia. Risk factors were documented in 90% of cases, risk factor intervention in 30%. The proportions of mild, moderate, severe dysplasia and CIS were consistent with other published series. Number of follow-up visits during the first two years correlated with dysplasia grade. When compared with an evidence-based protocol, total duration was of follow-up was short in over 80% of patients. Oral dysplasia was followed-up more frequently and longer than laryngeal dysplasia, but had a higher malignant transformation rate and shorter time interval to malignant progression. In both groups, progression was not associated with grade. Conclusion: Documentation of risk factors and intervention is poor. Dysplasias were not followed entirely according to evidence-based guidelines. We have commenced prospective review of our current practice. There is a need for more awareness amongst clinicians of the high potential for progression to cancer and of best evidence guidelines for follow-up. Keywords: dysplasia, follow-up, progression to SCC O85 Cell cycle protein expression patterns in HPV-containing and -lacking tonsillar squamous cell carcinomas and association with prognosis: a role for p21? J. Mooren1 *, J. Manni2 , H. Hafkamp2 , B. Klingenberg1 , A. Voogd1 , F. Bot2 , S. Claessen1 , A. Hopman1 , F. Ramaekers1 , B. Kremer2 , E.J. Speel1,2 . 1 University of Maastricht, Netherlands, 2 Academic Hospital Maastricht, Netherlands Purpose: Tonsillar squamous cell carcinoma (TSCC) may be induced by chemical carcinogens as a result of, e.g., tobacco and alcohol consumption, or by oncogenic human papillomavirus (HPV). HPV presence has been reported to be associated with a favorable patient survival. This study was undertaken because controversial data exist on the expression of key cell cycle proteins in the retinoblastoma (pRb) and p53 pathways in HPV-containing and -lacking TSCC and their impact on patient survival. Methods: Formalin-fixed, paraffin-embedded tissue sections (4 mm thick) of 77 TSCC were analyzed by immunohistochemistry for expression of ki-67, p16INK4A , cyclin D1, pRb, p14ARF , MDM2, p53, p21CIP1/WAF1 and p27KIP1 . The presence of biologically associated HPV16 was determined by HPV-specific fluorescence in situ hybridization. Results were correlated with each other and with patient survival. Results: 75 of 77 (97%) TSCC showed strong, nuclear Ki67 expression in 30 90% of tumor cells. 32 (42%) TSCC were HPV16-positive. The presence of HPV was significantly associated with overexpression of p16INK4A (p < 0.0001), p14ARF (p < 0.0001) and p21CIP1/WAF1 (p = 0.001), and downregulation of pRb (p < 0.0001). p53 and MDM2 accumulation tended to be associated with absence of HPV (P < 0.082). Accumulation of nuclear cyclin D1 and p27KIP1 was detected in 43% and 28% of the tumors, respectively, irrespective of HPV-status. Univariate Cox regression analysis revealed a favorable survival rate for non-smokers (p = 0.016), as well as for patients with TSCC, showing either low/no expression of cyclin D1 (p = 0.034), HPV presence (p = 0.029) or overexpression of p16INK4A (p = 0.035), p14ARF (p = 0.024) or, remarkably, p21CIP1/WAF1 (p = 0.007). Discussion: HPV 16-associated TSCC exhibit overexpression of p16INK4A , p14ARF and p21CIP1/WAF1 and downregulation of pRb. Strong immunostaining for p21CIP1/WAF1 appears to be the most optimal indicator for favorable prognosis in these tumors. Keywords: tonsillar squamous cell carcinoma, human papilloma virus, p21, cell cycle protein
Oral and Symposium abstracts, Saturday 19 May Data collection and Analysis: Identification through histology records. Notes were analysed and outcome measures recorded. Results: Of 149 cases, 31 were excluded and 4 lost to follow-up. 79 patients had dysplasia of the larynx; 35 had oropharyngeal dysplasia. Risk factors were documented in 90% of cases, risk factor intervention in 30%. The proportions of mild, moderate, severe dysplasia and CIS were consistent with other published series. Number of follow-up visits during the first two years correlated with dysplasia grade. When compared with an evidence-based protocol, total duration was of follow-up was short in over 80% of patients. Oral dysplasia was followed-up more frequently and longer than laryngeal dysplasia, but had a higher malignant transformation rate and shorter time interval to malignant progression. In both groups, progression was not associated with grade. Conclusion: Documentation of risk factors and intervention is poor. Dysplasias were not followed entirely according to evidence-based guidelines. We have commenced prospective review of our current practice. There is a need for more awareness amongst clinicians of the high potential for progression to cancer and of best evidence guidelines for follow-up. Keywords: dysplasia, follow-up, progression to SCC O85 Cell cycle protein expression patterns in HPV-containing and -lacking tonsillar squamous cell carcinomas and association with prognosis: a role for p21? J. Mooren1 *, J. Manni2 , H. Hafkamp2 , B. Klingenberg1 , A. Voogd1 , F. Bot2 , S. Claessen1 , A. Hopman1 , F. Ramaekers1 , B. Kremer2 , E.J. Speel1,2 . 1 University of Maastricht, Netherlands, 2 Academic Hospital Maastricht, Netherlands Purpose: Tonsillar squamous cell carcinoma (TSCC) may be induced by chemical carcinogens as a result of, e.g., tobacco and alcohol consumption, or by oncogenic human papillomavirus (HPV). HPV presence has been reported to be associated with a favorable patient survival. This study was undertaken because controversial data exist on the expression of key cell cycle proteins in the retinoblastoma (pRb) and p53 pathways in HPV-containing and -lacking TSCC and their impact on patient survival. Methods: Formalin-fixed, paraffin-embedded tissue sections (4 mm thick) of 77 TSCC were analyzed by immunohistochemistry for expression of ki-67, p16INK4A , cyclin D1, pRb, p14ARF , MDM2, p53, p21CIP1/WAF1 and p27KIP1 . The presence of biologically associated HPV16 was determined by HPV-specific fluorescence in situ hybridization. Results were correlated with each other and with patient survival. Results: 75 of 77 (97%) TSCC showed strong, nuclear Ki67 expression in 30 90% of tumor cells. 32 (42%) TSCC were HPV16-positive. The presence of HPV was significantly associated with overexpression of p16INK4A (p < 0.0001), p14ARF (p < 0.0001) and p21CIP1/WAF1 (p = 0.001), and downregulation of pRb (p < 0.0001). p53 and MDM2 accumulation tended to be associated with absence of HPV (P < 0.082). Accumulation of nuclear cyclin D1 and p27KIP1 was detected in 43% and 28% of the tumors, respectively, irrespective of HPV-status. Univariate Cox regression analysis revealed a favorable survival rate for non-smokers (p = 0.016), as well as for patients with TSCC, showing either low/no expression of cyclin D1 (p = 0.034), HPV presence (p = 0.029) or overexpression of p16INK4A (p = 0.035), p14ARF (p = 0.024) or, remarkably, p21CIP1/WAF1 (p = 0.007). Discussion: HPV 16-associated TSCC exhibit overexpression of p16INK4A , p14ARF and p21CIP1/WAF1 and downregulation of pRb. Strong immunostaining for p21CIP1/WAF1 appears to be the most optimal indicator for favorable prognosis in these tumors. Keywords: tonsillar squamous cell carcinoma, human papilloma virus, p21, cell cycle protein