Head and neck cancer.

Head and neck squamous cell carcinomas (HNSCCs) are caused by tobacco and alcohol consumption and by infection with high-risk types of human papillomavirus (HPV). Tumours often develop within preneoplastic fields of genetically altered cells. The persistence of these fields after treatment presents a major challenge, because it might lead to local recurrences and second primary tumours that are responsible for a large proportion of deaths. Aberrant signalling pathways have been identified in HNSCCs and inhibition of epidermal growth factor receptor (EGFR) has proved a successful therapeutic strategy. In this Review, we discuss the recent literature on tumour heterogeneity, field cancerization, molecular pathogenesis and the underlying causative cancer genes that can be exploited for novel and personalized treatments of patients with HNSCC.

The molecular biology of head and neck cancer

Background Patients with head-and-neck cancers who are free of disease after local therapy remain at high risk for both recurrent and second primary tumors Retinoids have proved efficacious in the treatment of premalignant oral lesions and are promising agents for the prevention of epithelial carcinogenesis Methods We prospectively studied 103 patients who were disease-free after primary treatment for squamous-cell cancers of the larynx, pharynx, or oral cavity After completion of surgery or radiotherapy (or both), these patients were randomly assigned to receive either isotretinoin (13-cis-retinoic acid) (50 to 100 mg per square meter of body-surface area per day) or placebo, to be taken daily for 12 months Results There were no significant differences between the two groups in the number of local, regional, or distant recurrences of the primary cancers However, the isotretinoin group had significantly fewer second primary tumors After a median follow-up of 32 months, only 2 patients (4

https://www.nejm.org/doi/pdf/10.1056/NEJM199009203231205

Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck.

Head and neck cancers include neoplasms of the oral cavity, pharynx, and larynx. The risk of these cancers is strongly associated with smoking and alcohol ingestion. There have been important advances in understanding of the molecular pathogenesis and progression of head and neck cancer and also in approaches to therapy, which include innovations in surgery, radiation therapy, and cytotoxic-drug therapy.

https://www.nejm.org/doi/pdf/10.1056/NEJMra001375?listPDF=true

The concept of "field cancerization" was first introduced by Slaughter et al. [D. P, Slaughter et al., Cancer (Phila.), 6: 963-968, 1953] in 1953 when studying the presence of histologically abnormal tissue surrounding oral squamous cell carcinoma. It was proposed to explain the development of multiple primary tumors and locally recurrent cancer. Organ systems in which field cancerization has been described since then are: head and neck (oral cavity, oropharynx, and larynx), lung, vulva, esophagus, cervix, breast, skin, colon, and bladder. Recent molecular findings support the carcinogenesis model in which the development of a field with genetically altered cells plays a central role. In the initial phase, a stem cell acquires genetic alterations and forms a "patch," a clonal unit of altered daughter cells. These patches can be recognized on the basis of mutations in TP53, and have been reported for head and neck, lung, skin, and breast cancer. The conversion of a patch into an expanding field is the next logical and critical step in epithelial carcinogenesis. Additional genetic alterations are required for this step, and by virtue of its growth advantage, a proliferating field gradually displaces the normal mucosa. In the mucosa of the head and neck, as well as the esophagus, such fields have been detected with dimensions of >7 cm in diameter, whereas they are usually not detected by routine diagnostic techniques. Ultimately, clonal divergence leads to the development of one or more tumors within a contiguous field of preneoplastic cells. An important clinical implication is that fields often remain after surgery of the primary tumor and may lead to new cancers, designated presently by clinicians as "a second primary tumor" or "local recurrence," depending on the exact site and time interval. In conclusion, the development of an expanding preneoplastic field appears to be a critical step in epithelial carcinogenesis with important clinical consequences. Diagnosis and treatment of epithelial cancers should not only be focused on the tumor but also on the field from which it developed.

https://cancerres.aacrjournals.org/content/canres/63/8/1727.full.pdf

A Genetic Explanation of Slaughter’s Concept of Field Cancerization: Evidence and Clinical Implications

https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/1097-0142%28195309%296%3A5%3C963%3A%3AAID-CNCR2820060515%3E3.0.CO%3B2-Q

“Field cancerization” in oral stratified squamous epithelium. Clinical implications of multicentric origin

â€ ̃¿ @ Data from Majarakis, Slaughter, and Cole. The subject of carcinoma of the thyroid gland has created more of a controversy in the literature in recent years than its numerical incidence warrants. Actually, thyroid cancer is one of the less common forms of malignant neoplastic disease. as compared with cancer of the skin, breast. lung, uterine cervix, and gastrointestinal tract. However, the importance of the problem lies in the fact that. froni this recent spate of published studies, a clinical pattern has evolved whereby one more form of major cancer can he recognized in an early, curable, and easily treatable stage. Furtherniore, it is entirely possible that this pattern of clinical approach may add thyroid cancer to the list of those ma lignant tumors to which the emerging con cept of true cancer prevention may he applicable.

Danely P. Slaughter

Papers

“Field cancerization” in oral stratified squamous epithelium. Clinical implications of multicentric origin

Carcinoma of the thyroid gland