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VCU Department of Otolaryngology, Virginia Commonwealth University VCU Department of Otolaryngology VCU Medical Center VCU

VCU Department of Otolaryngology

Head and Neck Surgical Oncology

Demographics

  • Head and neck carcinoma accounts for approximately 5.6% of all new cancers.
  • The gender ratio is 5:1 male to female but an increasing percentage of women are being affected. As an example, in 1990, 23% of patients presenting to MCV/VCU with laryngeal carcinoma were women. In 1995, female patients accounted for 46% of our new laryngeal cancer cases. This is most likely the result of increased cigarette consumption by women.
  • Overall, the incidence rate of laryngeal carcinoma has declined slightly nationwide to 3.8/100,000 persons. The incidence rate for Virginia is 4.6/100,000 persons. The highest rates for the state are in Norfolk (8.2/100,000 persons) and Richmond (7.1/100,000 persons). The lowest rate in the state is in Northern Virginia (2.7/100,000 persons).
  • Head and neck cancer is generally considered a disease of the 5th and 6th decade of life although it does occur at younger ages.

 

Risk Factors and Etiology

Cigarettes and alcohol

Head and neck cancer is primarily a disease of cigarette and alcohol consumption. Moreover, a synergistic effect seems to exist between alcohol and tobacco with regards to carcinogenesis. Accordingly, until recently, the incidence of laryngeal carcinoma has increased for both men and women, but overall the increase has been greater for women. By contrast, malignant salivary gland tumors are not believed to be related to cigarette consumption, and have declined in the general population. It is important to note that cigarette use carries with it the risk of multiple primary tumors and about 10% of head and neck cancer patients manifest second tumors at the time of presentation.

Cigarette smoking is addictive and roughly 40% of patients treated for head and neck cancer continue to smoke. In a study recently published by the Department of Otolaryngology - Head and Neck Surgery at MCV/VCU, the cessation rate for head and neck cancer patients was 69% at 18 months after a cancer diagnosis. (Laryngoscope, 107:888-892, 1997) Treatment using combined modality therapy (radiation and surgery with or without chemotherapy) and total laryngectomy were positive predictors for smoking cessation. Past excessive alcohol consumption was a negative predictive factor. Unfortunately, as a consequence, patients with early stage lesions who are the most likely to benefit from prolonged smoking cessation are the least likely to quit. Frequent, short duration counseling beginning at the time of tumor diagnosis was found to be the best practical approach to achieve smoking cessation in head and neck cancer patients.

Interestingly, the number of cigarettes consumed by the average smoker has increased dramatically over the years. The average number of cigarettes consumed daily in 1935 was approximately 11.5 and increased to 33.3 in 1979. This may be attributed to the increasing use of filtered cigarettes. While smokers now inhale less smoke per cigarette the number of cigarettes consumed has consequently increased. The proportion of low tar cigarettes in the marketplace has also increased. Unfortunately, the definition of low tar is arbitrarily set at 15 mg per cigarette and recent evidence has suggested that decreased tar has not led to a diminution in the incidence of smoking related diseases.

Approximately 75 to 80% of all patients with oral carcinoma are noted to consume alcohol, particularly hard liquor. The disease is six times more common in drinkers than non-drinkers. Alcohol probably acts in various ways to induce oral carcinoma. First, ultrastructural analysis of the oral mucosa in non-smoking alcoholic patients demonstrates epithelial dysplasia, including an increase in nuclear atypia, prominent nucleoli and fragmentation of the basal cell layer. This suggests that alcohol alone is carcinogenic. Alcohol and tobacco, as mentioned, are synergistic in the induction of carcinoma. This may be related to increased solubility of tobacco related carcinogens. Finally, alcohol is known to cause nutritional deficiencies, which may result in diminished immune response to cancerous cells.

Smokeless tobacco

Despite overall little change in the rate of smokeless tobacco use, there has been a marked change in the age distribution of the users. In particular, consumption in the age group of 40 years and above has diminished while regular use by children in grades three to twelve is estimated at 17% for boys and 2% for girls. Over six million Americans above the age of 12 years are regular users. Smokeless tobacco has been directly linked to oral carcinomas.

Human Papilloma Virus (HPV 16 and 18)

Human papilloma virus is widely distributed and has species and site specificity. Human papilloma virus affects the skin, anogenital epithelium, and upper aerodigestive tract epithelium and is associated with various histologic lesions at these sites. HPV 6, 11, 16, and 18 are often isolated from the genital and aerodigestive tract. HPV 6 and 11 are usually associated with benign lesions such as papillomata. HPV 16 and 18 have been identified in premalignant and malignant lesions. It has been proposed that the reservoir for HPV 6, 11, 16, 18, 31, 32, and 35 is the anogenital region and HPV 1, 2, 3, 4, and 5 reside in the skin. Further analysis of the role of HPV in head and neck cancer is ongoing.

Other

More than one third of patients with carcinoma of the lip have an outdoor occupation. Prolonged exposure to sunlight seems to play a major role in the genesis of squamous cell carcinoma of the lip, especially the lower lip. Syphilis was thought previously to play an important role in oral carcinoma but less so today. Poor oral hygiene may be an etiologic factor in the development of oral cavity cancer. Ill fitting dentures and jagged fractured teeth causing chronic mucosal irritation have also been implicated in the genesis of oral carcinoma. Dietary deficiencies such as iron deficient anemia and riboflavin deficiency have been noted. Even recurrent herpes stomatitis type-I has been observed in patients with oral carcinoma. Finally, environmental carcinogens such as sulfa, petroleum products and epoxy resins are suspect in head and neck carcinoma.

 

Histopathology

  • Histology (microscopic cellular appearance)

    Normally, ciliated pseudostratified columnar epithelial cells line the respiratory tract with the exception of the vocal cords, which are covered by non-keratinizing squamous epithelium. The remainder of the upper aerodigestive tract, including the pharynx is also covered by non-keratinizing squamous epithelium. Premalignant lesions demonstrate hyperkeratosis, hyperplasia and dysplasia. The terms leukoplakia and erythroplakia are gross descriptions meaning white plaque and red plaque respectively and not histologic diagnoses. Moreover, 10% of leukoplastic lesions are noted to contain malignant cells as opposed to 30% of erythroplastic lesions. The majority of head and neck cancers arise from this squamous epithelium and are called squamous cell carcinoma .

 

Parameters of Prognosis

  • Tumor stage is of primary importance in determining treatment options and the prognosis of head and neck carcinoma. The TNM system is used. The T signifies the tumor size, N the status of the neck lymph nodes, and M the presence or absence of distant metastatic disease. It is important to note that once regional lymph node involvement occurs, the survival rate drops by 50%.
  • Tumor differentiation (how much like normal cells the tumors appears) while useful is not as important a prognostic factor. This is certainly true with squamous cell carcinoma.
  • Tumor host interactions may be important in the prognosis of head and neck cancer. The manner and extent to which the immune system responds to cancer is of interest. Studies, including those examining tumor associated tissue eosinophilia (TATE) have demonstrated some fascinating results.
  • The more eosinophilic infiltration (a type of white blood cell) of the tumor, the better the prognosis. Presumably, this indicates a greater host response to tumor.
  • On the other hand, diffuse inflammatory and fibrous tissue infiltration at the tumor site known as desmoplastic reaction is thought to indicate a worse prognosis.
  • Perineural invasion at the tumor site (extension of tumor around nerves) has been associated with more extensive local and regional disease and therefore a worse prognosis.
  • Vascular invasion (extension into blood vessels) is an important step in the development of metastasis. Although most circulating tumor cells do not develop into metastasis, the greater the number released into the vascular system the higher the likelihood.

 

Presentation and Warning Signs

  • Primary tumor location (where the tumor started)
    • Specific head and neck tumors often have a distinctive history at presentation. Vocal changes lasting more than two weeks in a smoker should elicit an examination for laryngeal carcinoma. Given this early symptom, patients tend to present earlier with laryngeal carcinoma than with other lesions of the head and neck and therefore often have a better prognosis. Moreover, the lymphatic supply to the larynx is not as great as in other head and neck regions and therefore regional metastasis may occur later.
    • Difficulty swallowing may be the initial presentation for pharyngeal (upper throat) or hypopharyngeal (lower throat) tumors; however, a common presentation for hypopharyngeal lesions is the unfortunate finding of a metastatic neck node. Non-healing oral ulcers are suspicious for oral carcinoma. On physical examination squamous cell carcinoma of the head and neck may appear as an exophytic (a mass), ulcerative ( a crater) or infiltrative (diffuse thickening) lesion.
  • Metastatic disease (spread of tumor)
    • Metastatic disease in the head and neck tends to occur in a predictable and systematic fashion. Regional neck metastasis most commonly occurs to the jugular digastric lymph nodes, but various lymph node chains might be affected depending on the primary tumor location and size.

      For example, oral carcinomas have a tendency to spread to the submandibular and submental (under the jaw bone) lymph nodes on both sides of the neck. Meanwhile, laryngeal carcinomas usually demonstrate initial neck metastasis to the jugular digastric (mid-neck) lymph nodes. Oral carcinomas have a tendency to metastasize earlier than laryngeal carcinomas with approximately 35% lymph node involvement at initial presentation. Metastasis to the supraclavicular( above the collar bone) region indicates a poor prognosis as does large cervical metastasis or bilateral neck disease. Distant metastasis most often manifests in the lungs followed by the liver, bone and brain. Overall, approximately 15 to 20% of patients with head and neck cancer manifest distant metastasis at presentation or within six months of diagnosis.

 

Diagnostic Evaluation

Given the above information, a systematic diagnostic evaluation has evolved.

  • Panendoscopy and biopsy
    Patients undergo open endoscopy, not only to evaluate the extent of the tumor and confirm the histology, but also to exclude the occurrence of additional primary lesions.
  • Radiographs
    A chest x-ray is useful as an initial screening test for metastatic lung disease or a second primary lung tumor. In addition, modern imaging techniques, including CT (computed tomography) scans and MRI scans, are used as an aid in staging head and neck tumors and planning treatment.
  • Liver function tests
    Liver function tests (blood tests) remain as the screening evaluation for liver metastasis although if liver lesions are suspected much more accurate testing, including CT scanning or liver spleen scanning may be employed.
  • Bone scan
    Bone scans are used when clinically indicated by the presence of skeletal pain or pathologic fractures.
  • PET scan
    Positron emission tomography is increasingly being used in patients with identifiable neck metastases to search for an unknown primary tumor, or to evaluate for recurrent tumor in individuals that are difficult to assess due to previous therapy. It also has a role in defining distant metastases. The recent addition of combined PET/CT scanning has further improved this modality's accuracy.

 

Treatment and Survival

Two major modalities are currently employed in the treatment of squamous cell carcinoma of the head and neck: surgery and radiation therapy. Chemotherapy has been utilized as induction therapy or as an adjunct with mixed results. More promising results are being obtained with combined chemotherapy and radiation therapy.

  • Surgery
    Surgery alone is generally reserved for early tumors in regions where significant functional and cosmetic deficits will not result from this treatment.
  • Radiotherapy
    Radiation therapy may be used alone in early tumors, most notably in early laryngeal cancer in order to preserve laryngeal function. It may also be used alone for unresectable tumors. In this instance it may be considered a palliative treatment and not intended as a cure.
  • Combined therapy
    Surgery and radiation are often used together in more advanced lesions. As combined treatment has evolved surgery with postoperative radiation therapy is most often employed. Recent advances in reconstructive surgery have further improved functional and cosmetic outcomes.

    In select instances, promising results are being obtained with combined chemotherapy and radiation therapy in an effort to avoid surgical resection.
  • Chemotherapy
    Although initial good responses have been obtained with induction chemotherapy the long-term outcomes are unclear. In general, it is not recommended to use chemotherapy as a sole treatment with curative intent for head and neck squamous cell carcinoma.

 

The Future

  • Organ preservation
    Ongoing research is being conducted into the use of organ preserving treatment such as combined chemotherapy and radiation therapy in advanced laryngeal carcinoma to avoid surgical removal of the voice box.
  • Cellular and genetic research
    Tremendous effort is being expended in the arena of cellular genetics. Future breakthroughs are likely to occur in this area.
  • Prevention
    A major blow to head and neck cancer could be struck if prevention of the disease is pursued. In particular, while the percentage of adults using cigarettes has declined, many youths continue to pursue the habit as do more women and minorities. Similar statements may be made about the consumption of alcohol.