Head and neck cancer.

c-myc, N-myc and L-myc are the three members of the myc oncoprotein family whose role in the pathogenesis of many human neoplastic diseases has received wide empirical support. In this review, we first summarize data, derived mainly from non-clinical studies, indicating that these oncoproteins actually serve quite different roles in vivo. This concept necessarily lies at the heart of the basis for the observation that the deregulated expression of each MYC gene is reproducibly associated with only certain naturally occurring malignancies in humans and that these genes are not interchangeable with respect to their aberrant functional consequences. We also review evidence implicating each of the above MYC genes in specific neoplastic diseases and have attempted to identify unresolved questions which deserve further basic or clinical investigation. We have made every attempt to review those diseases for which significant and confirmatory evidence, based on studies with primary tumor material, exists to implicate MYC members in their causation and/or progression.

MYC oncogenes and human neoplastic disease

Head and Neck Cancer Most head and neck cancers (73% in the United States) are now related to human papillomavirus infection rather than tobacco and alcohol. Primary cancers are largely squamous-ce...

https://www.nejm.org/doi/pdf/10.1056/NEJMra1715715

Head and Neck Cancer

Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity.

Risk factors for squamous cell carcinoma of the oral cavity in young people--a comprehensive literature review.

57 primary tumour samples from Indian oral cancer patients with a 5-15 year tobacco chewing habit, were examined for mutational activation in codons 12, 13 and 61 of the H-ras, K-ras and N-ras oncogenes. The highly sensitive assay based on specific oligonucleotide hybridisation following in vitro amplification of unique sequences by polymerase chain reaction was employed. Mutations were detected in twenty (35%) of the samples and were restricted to H-ras, codons 12, 13 and 61. Two cases had concurrent mutations in codons 12 and 61. The majority of the mutations were at H-ras 61.2 (Glutamine to Arginine) and H-ras 12.2 (Glycine to Valine). Three of the less frequent mutations are apparently novel. Interestingly, eight of the samples with H-ras mutations also showed loss of wild-type H-ras, as judged by absence of signals for wild-type codons 12 or 61 on dot blots. The specific H-ras mutations in these oral malignancies associated with tobacco chewing, may represent an important example of an environmental carcinogen-induced step, in a pathway leading to malignant transformation.

High frequency mutation in codons 12 and 61 of H-ras oncogene in chewing tobacco-related human oral carcinoma in India.

Detection of HPV-16 genome in human oral cancers and potentially malignant lesions from India

We have determined the prevalence of amplification of c-myc, N-myc, L-myc, H-ras, Ki-ras, and N-ras oncogenes in 23 cases of squamous cell carcinoma of the oral cavity, using Southern hybridization analysis of DNA extracted from the primary tumor tissues. Nick-translated oncogene probes and oncogene inserts labeled to high specific activities were used. We observed a 5- to 10-fold amplification of one or more of c-myc, N-myc, Ki-ras and N-ras oncogenes in 56% of the tumor tissue samples, with these oncogenes not being amplified in the peripheral blood cells of the same patients. L-myc and H-ras were not amplified in any of our samples. The oncogene amplifications seemed to be associated with advanced stages of squamous cell carcinomas, with the ras and myc family oncogenes being amplified in stages 3 and 4. Hybridization with N-myc detected an additional 2.3 kb EcoRI fragment, along with the normal 2.1 kb fragment. Our data also demonstrated amplification of multiple oncogenes in the same tumor tissue sample. About 60% of the samples with amplified oncogenes showed simultaneous amplification of 2 or more oncogenes. The results showing different oncogene amplifications in similar tumors, as well as multiple oncogene amplifications in the same tumor, suggest that these oncogenes may be alternatively or simultaneously activated in oral carcinogenesis.

Oncogene amplification in squamous cell carcinoma of the oral cavity

A prospective study of 220 consecutive pectoralis major myocutaneous flaps used for oral cavity reconstruction from March of 1990 to February of 1991 showed that 89 patients (40.5 percent) developed flap-related complications and 33 patients (15 percent) had complications unrelated to the flap; 92 patients (42 percent) had an uneventful recovery and there were 6 (2.7 percent) postoperative deaths. Sixty patients (27 percent) developed flap necrosis, of whom only 6 (2.7 percent) had total flap loss. Major partial loss occurred in 20 patients (9 percent) and minor flap loss occurred in 34 (15.5 percent). Flap necrosis was significantly lower in the purely myocutaneous flaps (p < 0.00000) vis-a-vis the bipedicled and osteocutaneous flaps. Fistula formation, wound infection, dehiscence at the flap margin, and postoperative hematomas occurred with comparable frequency in both groups. The female gender, primary tongue cancer, subtotal or total glossectomy, bipedicling of flaps, prior chemotherapy, and presence of systemic disease (diabetes) emerged as significant risk factors for flap necrosis on multivariate analysis (p < 0.005).

Ashok R. Mehta

Papers

High frequency mutation in codons 12 and 61 of H-ras oncogene in chewing tobacco-related human oral carcinoma in India.

Detection of HPV-16 genome in human oral cancers and potentially malignant lesions from India

Oncogene amplification in squamous cell carcinoma of the oral cavity

Complications of the pectoralis major myocutaneous flap in the oral cavity: a prospective evaluation of 220 cases.

p53 inactivation in chewing tobacco-induced oral cancers and leukoplakias from India