Publications of Faculty of Medicine:Human Papillomavirus High-risk Genotypes: Relationship to Apoptosis and p53 Expression in Egyptian Patients with Laryngeal Carcinoma: Abstract

Human Papillomavirus High-risk Genotypes: Relationship to Apoptosis and p53 Expression in Egyptian Patients with Laryngeal Carcinoma
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Human papillomavirus (HPV) infection is suspected of causing laryngeal carcinoma. The relationship of HPV-16 and 18 genotypes to apoptosis and p53 protein expression in Egyptian laryngeal carcinoma patients was studied. Biopsy specimens from 82 patients with laryngeal carcinoma and 28 with minimal pathological lesions serving as a control group were examined. In all specimens, HPV-16 and-18 were examined using PCR, p53 expression was studied by immunohistochemistry and DNA fragmentation to assess apoptosis was assayed using a biochemical method and gel electrophoresis. HPV-16 was detected in 51.2% of laryngeal carcinoma patients versus 14.3% of the control group (p=0.001). The surrounding areas of positive tumors were negative in 524% of them. HPV-16 was significantly higher in tumors with higher expression of p53 (p=0.026). An inverse significant relationship was found between HPV-16 and DNA fragmentation in the laryngeal carcinoma group (p=0.022). HPV-18 was detected in only 24% of laryngeal carcinoma patients. p53 protein was expressed in 76.8% of the malignant group with significant increasing positivity with increasing stage of the disease (p =am). Non of the control group was p53-positive. Our results suggest that highly oncogenic types of HPV may play a role in the pathogenesis of laryngeal carcinoma through inactivation of wild-type p53 with subsequent decrease in apoptosis and by induction of p53 mutation, which itself can induce malignant transformation. Increasing evidence suggests that human papillomavirus (HPV) infection is associated with an increased risk of epithelial cancer (1). HPV is a small ( — 7,900 base pairs) double-stranded circular DNA virus belonging to papovaviruses. It is capable of infecting epithelial cells Correspondence to: Samar K. Kassim, Medical Biochemistry Department, Ath Shams Faculty of Medicine, Cairo, Egypt. e-mail: Key Words: HPV-16, HPV-18, apoptosis, p53, laryngeal carcinoma. resulting in a variety of pathological lesions. Under certain yet unknown circumstances, the viral genome may become integrated into the cellular genome, which may lead to malignant transformation (2). Laryngeal cancer is one of those pathological lesions related to HPV infection (3). Among the more than 100 different types of HPV identified, type 16 is the most common high-risk genotype (4). Type 18 is another high-risk genotype (3). The viral genome contains coding regions referred to as open reading frames (ORFs). ORFs that encode nonstructural proteins are referred to as early (E) genes and those that encode structural proteins are termed late (L) genes, in accordance with the time in the viral life cycle that they are expressed (5). Integration disrupts the viral genome in the E1-E2 region, resulting in the failure of transcription of the late genes and possibly in uncontrolled transcription of the E6 and E7 genes (2). Expression of the E6 and E7 proteins of HPV-16 and 18 is sufficient for the immortalization of primary human epithelial cells and induces premalignant 1-WV-associated squamous intra-epithelial lesions (6). It has been well documented that E6 and E7 oncoproteins alter normal cell growth control mechanisms by inactivating two well-characterized tumor suppressor proteins, p53 and retinoblastoma protein, respectively (7). p53 is a cell cycle "checkpoint" protein, important for cell cycle regulation and is functionally inactivated in human cancer at a high frequency (8). The E6 protein of HPV-16 and 18 binds to p53 and targets it for degradation through the ubiquitin pathway (9). E6 viral protein has additional biological and transforming activities that appear independent of p53 (10). It has been reported to interact with a number of cellular proteins including proteins involved in apoptosis such as Bak (11), c-Myc (12) and tumor necrosis factor (TNE)(13). In the present work, we studied the incidence of HPV infection among laryngeal cancer patients in Egypt. The relationship of the HPV genotypes 16 and 18 to apoptosis and p53 protein expression in laryngeal tumor tissues in comparison to benign lesions was addressed. 1109-6535/2004 $2.00+ .40