P16 expression in subsets of Head and Neck squamous Cell Carcinoma in Kenyatta National Hospital
Background: Traditionally head and neck squamous cell carcinoma (HNSCC) has been regarded as a homogenous group of tumours that differ only by anatomic site. However, numerous studies have indicated that this is not the case. Recognition of distinct molecular profiles now allows further classification of HNSCC into distinct subgroups that differ with respect to risk factors, pathogenesis, and clinical behavior. Among these subgroups is the Human papilloma virus (HPV) associated HNSCC which have been found to differ from the non HPV-associated HNSCC in that HPV-HNSCC affects younger patients, respond better to chemotherapy and radiotherapy and have a better 5 year survival rate independent of tumour stage. These subgroups cannot be readily differentiated morphologically on routine Hematoxylin and Eosin (H/E).Cellular tumour markers such as P16 Immunohistochemistry may be used to separate these groups of tumours. This study set out to identify the HPV associated HNSCC by P16 immunohistochemistry. This is due to the over expression of P16 tumour suppressor protein P16INK4A in these tumours. Several studies have found P16 immunohistochemistry has high sensitivity, specificity, positive and negative predictive value of P16 expression in relation to HPV status. P16 immunohistochemistry has been found to be a more cost effective method and it has been proposed to be used as a 1st line marker Objective: To determine P16 expression and the prevalence of HPV- associated tumours in subsets of Head and Neck Squamous cell carcinoma (Oral, Oropharyngeal, Laryngeal carcinomas) reported at KNH. Design: Laboratory-based, descriptive cross sectional study. Setting: The University of Nairobi (UON), Department of Human Pathology, and the Kenyatta National Hospital (KNH) Nairobi, Kenya Study population: A hundred and three cases reported as HNSCC (Oral, Oropharyngeal, Laryngeal carcinomas) Methods: A hundred and three previously diagnosed HNSCC from 2008-2013 were analyzed for P16 expression by Immunohistochemistry on formalin fixed paraffin wax embedded tumor tissue blocks. P16 expression was correlated with age, sex, anatomic site of tumor and histological differentiation. Results xi The majority were males 76(74%) while females accounted for 27(26%). M: F was 2.8:1. Mean age was 57.4 with (SD 14).Most of the tumours were from the oral cavity 45(43.7%) followed by larynx 39(37.9%) and pharynx 19(18.4%). Majority of the tumours were well differentiated 65(63 %) followed by the moderately well differentiated tumours 29 (28%), while the poorly differentiated tumours were 8 (8%).Immunohistochemistry was carried out in all the cases, 15 (15%) were found to be positive for P16. The oral cavity had the highest frequency 7(46.67%), followed by larynx 4(26.67%) and lastly pharynx 4(26.67%).Majority of p16 positive HNSCC were found in males 10(67%). With regard to age, the highest frequency of p16 HNSCC occurred in those more than 60years 6 (40%), followed by 51-60 age group 5 (33%).However when cases are reclassified to above 60 years and below 60 years of note is the below 60 year cases are the majority (60%). Majority of the p16 positive HNSSC were well differentiated 9 (60%) followed by the moderately well differentiated carcinomas 4(26%). The poorly differentiated tumours had an increased likelihood of having HPV (OR 2.1, 95% C.I 0.4-11.9).
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