Detection of Human Papillomavirus and Relevant Tumor Suppressors and Oncoproteins in Laryngeal Tumors

Abstract

Purpose: The mechanism of larynx oncogenesis is complex and controlled by various factors, most of them involved in cell proliferation and apoptosis. In this study, we evaluated the levels of two suppressor proteins (pRb and p53) and two oncogenic proteins (c-Myc and Bcl-2), as well as the apoptotic levels and the presence of human papillomavirus (HPV) in both tumor types. Experimental Design: Low-or high-risk HPV viral DNA was determined by PCR and in situ PCR; the level of cellular proteins was examined by immunohistochemistry; the presence of apoptotic cells was evaluated by in situ cell death detection. Results: Most laryngeal papillomatosis samples contained low-risk HPV determined by both techniques. However, 25% of laryngeal carcinoma samples were positive for HPV employing PCR or in situ PCR. In papillomatosis, pRb and p53 levels were higher than in normal larynxes, whereas laryngeal cancer presented the lowest levels. c-Myc oncogene expression was very low in normal and cancer tissues but highly increased in papillomatosis. Bcl-2 expression was low and showed no significant difference between laryngeal papillomatosis and normal larynxes. By contrast, Bcl-2 was clearly up-regulated in cancer. Normal larynx samples and those from laryngeal papillomatosis exhibited similar relatively high numbers of apoptotic cells, whereas in malignant tumors, these cells were scarce. Conclusion: Our results suggest that HPV is an important risk factor in papillomatosis and in some malignant larynx tumors with a strong participation of cellular genes, specifically involved in proliferation and apoptosis. In benign papillomatosis lesions but not in larynx cancer, high p53 activity might preserve the apoptosis process. In larynx cancer, low p53 levels and high bcl-2 expression may be playing an important role to block apoptosis.Laryngeal carcinoma is a common malignant tumor of the head and neck (1). Besides well-established risk factors like smoking and alcohol abuse (1, 2), the development of laryngeal carcinoma is associated with human papillomavirus (HPV) infection (2, 3). On the other hand, mother-to-child transmission is probably responsible for recurrent laryngeal and pulmonary papillomatosis in infants (4), and actually laryngeal papillomatosis is the most common benign tumor of the larynx in children (5, 6). Laryngeal papillomatosis is induced by low-risk HPV, especially types 6 and 11, and is characterized by recurrence (5, 6). The clinical course is unpredictable but regression may occur following some treatments (7 -9). However, in other cases, the disease has a more aggressive course, recurs more frequently, and can extend well into adult life, requiring repeated surgical procedures. In a small number of patients, laryngeal papillomatosis may develop into squamous cell carcinoma (7 -9).HPV-16 is the most common high-risk virus. Its contribution to neoplastic progression is predominantly through the action of the viral oncoproteins E6 and E7 (10 -14). Expression of these proteins is sufficient for the i...

Two different HPV-11E6 fusion proteins trap p53 in the cytoplasm and induce apoptosis

“…This was supported by Manjarrez, who showed that in papillomatosis, p53 levels were higher than in normal larynxes, indicating that p53 activity might preserve the apoptosis process. 33 Furthermore, the other apoptosis associated proteins, such as bax, Bak, cmyc and cdc2 were also increased in HPV-11E6 expressed cells compared with control cells.…”

Human Papillomavirus in Non-Oropharyngeal Head and Neck Cancers: A Systematic Literature Review

“…The following arbitrary restraints were placed on this review; we excluded nonEnglish manuscripts, manuscripts published before 2000, case reports, and investigations using non-PCR techniques or only in-situ PCR. If data were available using multiple techniques, only the PCR-generated data were extracted [1]. Only data generated from primary squamous cell carcinomas (SCC) were extracted, and we excluded reports if: (1) the detection methods were not well-detailed, and/or (2) HPV data could not be extracted per anatomic site.…”

Low and High Risk Human Papillomavirus in the Oral Mucosa of Mexican Women with Genital Papillomavirus

“…In Mexico, cervical-uterine cancer (CUC) is the most frequent sexually transmitted viral disease and cause of death in women older than 25 years [3,4]. A link between HPV and squamous cell carcinoma of the head and neck was suggested more than 20 years ago [5]. Investigators showed a strong association between high-risk HPV infection and oral squamous cell carcinoma in Mexican, Sweden Japanese, and Chinese populations [5][6][7][8].…”

“…A link between HPV and squamous cell carcinoma of the head and neck was suggested more than 20 years ago [5]. Investigators showed a strong association between high-risk HPV infection and oral squamous cell carcinoma in Mexican, Sweden Japanese, and Chinese populations [5][6][7][8]. So HPV infection is not limited to the genital tract; it can extend to extragenital sites and particularly to the oral cavity, but the mechanism of infection of HPV into the oral mucosa remains unknown.…”

“…The high risk HPV genotypes 16 and 18 are the most common, and have been detected in 95% of women with CUC [17]. Recent studies indicate that these two genotypes are also related with oral cancer or with neck and head cancer [2,5,[19][20][21]. Besides, some risk factors such as smoking, alcohol consumption and sexual habits have also been associated to oral cancer [22][23][24][25][26][27].…”