Head and neck cancer

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**Head and neck cancer**
*Classification & external resources*
ICD-10	C07-C14, C32, C33

Head and neck cancers are malignant growths originating in the lip and oral cavity (mouth), nasal cavity, pharynx, larynx, thyroid, paranasal sinuses, salivary glands and cervical lymph nodes of the neck. Head and neck cancers are most commonly squamous cell carcinomas, originating from the squamous cells that line the upper aerodigestive tract.

[edit] Tumor locations

The term throat cancer is sometimes used as a layman's term for a cancer of the larynx or pharynx, a cancer that has metastasized to the lymph nodes of the neck, or even esophageal cancer. Epithelial neoplasms of the head and neck arise from the mucosal surfaces in the head and neck area and typically are squamous cell in origin. This category includes tumors of the paranasal sinuses, the oral cavity, and the nasopharynx, oropharynx, hypopharynx, and larynx. Tumors of the salivary glands differ from the more common carcinomas of the head and neck in etiology, histopathology, clinical presentation, and therapy. Other tumors arising in the head and neck include adenocarcinomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas. Rarer still are melanomas and lymphomas of the upper aerodigestive tract.

[edit] Oropharynx

(C10) Oropharyngeal cancer begins in the oropharynx, the middle part of the throat that includes the soft palate, the base of the tongue, and the tonsils.

[edit] Nasopharynx

(C11) Nasopharyngeal cancer begins in the nasopharynx, the upper part of the throat behind the nose.

[edit] Hypopharynx

The hypopharynx includes the pyriform sinuses, the larynx, the posterior pharyngeal wall, and the postcricoid area. Tumors of the hypopharynx frequently have an advanced stage at diagnosis, and have the most adverse prognoses of pharyngeal tumors. They tend to metastasize early due to the extensive lymphatic network around the larynx. (C32) Laryngeal cancer begins in the larynx, the part of the throat that contains the vocal cords and is used for breathing, swallowing, and talking.

[edit] Nasal cavity tumors

[edit] Oral cavity tumors

[edit] Salivary gland tumors

(C07-C08) The salivary glands give rise to a variety of uncommon tumours including adenocarcinomas, pleomorphic adenomas, and adenoid cystic carcinomas.

[edit] Tracheal cancer

(C33) Cancer of the trachea is a rare cancer that may also be considered throat cancer.

[edit] Incidence and Epidemiology

The number of new cases of head and neck cancers in the United States was 40,490 in 2006, accounting for about 3% of adult malignancies. 11,170 patients died of their disease in 2006.^[1]. The worldwide incidence exceeds half a million cases annually. In North America and Europe, the tumors usually arise from the oral cavity, oropharynx, or larynx, whereas nasopharyngeal cancer is more common in the Mediterranean countries and in the Far East. In Southeast China and Taiwan, head and neck cancer, specifically Nasopharyngeal Cancer is the most common cause of death in young men. ^[2] African Americans are disproportionately affected by head and neck cancer, with younger ages of incidence, increased mortality, and more advanced disease at presentation. ^[3]

[edit] Etiology

Alcohol ^[4] and tobacco use are the most common risk factors for head and neck cancer in the United States. Alcohol and tobacco are likely synergistic in causing cancer of the head and neck. ^[5] Smokeless tobacco is an etiologic agent for oral and pharyngeal cancers.^[6] Cigar smoking is an important risk factor for oral cancers as well.^[7] Other potential environmental carcinogens include marijuana and occupational exposures such as nickel refining, exposure to textile fibers, and woodworking. Cigarette smokers have a lifetime increased risk for head and neck cancers that is 5- to 25-fold increased over the general population.^[8] The ex-smoker's risk for squamous cell cancer of the head and neck begins to approach the risk in the general population twenty years after smoking cessation. The high prevalence of tobacco and alcohol use worldwide and the high association of these cancers with these substances makes them ideal targets for enhanced cancer prevention.

Dietary factors may contribute. Excessive consumption of processed meats and red meat were associated with increased rates of cancer of the head and neck in one study, while consumption of raw and cooked vegetables seemed to be protective.^[9] Vitamin E was not found to prevent the development of leukoplakia, the white plaques that are the precursor for carcinomas of the mucosal surfaces, in adult smokers. ^[10] Another study examined a combination of Vitamin E and beta carotene in smokers with early-stage cancer of the oropharynx, and found a worse prognosis in the vitamin users. ^[11]

Betel-nut chewing is associated with an increased risk of squamous cell cancer of the head and neck. ^[12]

Some head and neck cancers may have a viral etiology. The DNA of human papillomavirus has been detected in the tissue of oral and tonsil cancers, and may predispose to oral cancer in the absence of tobacco and alcohol use. Epstein-Barr virus (EBV) infection is associated with nasopharyngeal cancer. ^[13] Nasopharyngeal cancer occurs endemically in some countries of the Mediterranean and Asiat, where EBV antibody titers can be measured to screen high-risk populations. ^[14] Nasopharyngeal cancer has also been associated with consumption of salted fish, which may contain high levels of nitrites.

[edit] Prognosis and staging

Although early-stage head and neck cancers (especially laryngeal and oral cavity) have high cure rates, up to 50% of head and neck cancer patients present with advanced disease. ^[15] Cure rates decrease in locally advanced cases, whose probability of cure is inversely related to tumor size and even more so to the extent of regional node involvement. Consensus panels in America (AJCC) and Europe (UICC) have established staging systems for head and neck squamous cancers. These staging systems attempt to standardize clinical trial criteria for research studies, and attempt to define prognostic categories of disease. Squamous cell cancers of the head and neck are staged according to the TNM classification system, where T is the size and configuration of the tumor, N is the presence or absence of lymph node metastases, and M is the presence or absence of distant metastases. The T, N, and M characteristics are combined to produce a “stage” of the cancer, from I to IVB. ^[16]

[edit] Diagnosis

[edit] Symptoms

Presenting symptoms include

Mass in the neck
Neck pain
Swallowing difficulty (dysphagia)
Painful swallowing (odynophagia)
Weight loss
Bleeding from the mouth
Sinus congestion, especially with nasopharyngeal carcinoma

[edit] Diagnostic approach

A patient usually presents to the physician complaining of one or more of the above symptoms The patient will typically undergo a needle biopsy of this lesion, and a histopathologic diagnosis thereby made. Imaging studies such as CT Scans, MRIs of the neck, or combined PET-CT scans are critical in assessing for local or regional metastasis. Finally, after all the staging information is available, a multidisciplinary discussion of the optimal treatment strategy will be undertaken between the radiation oncologist, surgical oncologist, and medical oncologist.

[edit] Head and Neck Cancer Treatment

[edit] General considerations

Improvements in diagnosis and local management, as well as targeted therapy, have led to improvements in quality of life and survival for head and neck cancer patients since 1992 ^[17]

After a histologic diagnosis has been established and tumor extent determined, the selection of appropriate treatment for a specific cancer depends on a complex array of variables, including tumor site, relative morbidity of various treatment options, patient performance and nutritional status, concomitant health problems, social and logistic factors, previous primary tumors, and patient preference. Treatment planning generally requires a multidisciplinary approach involving specialist surgeons and medical and radiation oncologists.

Several generalizations are useful in therapeutic decision making, but variations on these themes are numerous. Surgical resection and radiation therapy are the mainstays of treatment for most head and neck cancers and remain the standard of care in most cases. For small primary cancers without regional metastases (stage I or II), wide surgical excision alone or curative radiation therapy alone is used. More extensive primary tumors, or those with regional metastases (stage III or IV), planned combinations of pre- or postoperative radiation and complete surgical excision are generally used. Survival and recurrence risk has been roughly equivalent between surgical and radiation-based approaches, with a head-to-head comparison in only one randomized study^{[citation needed]}. More recently, as historical survival and control rates are recognized as less than satisfactory, there has been an emphasis on the use of various induction or concomitant chemotherapy regimens.

Patients with head and neck cancer can be categorized into three clinical groups: those with localized disease, those with locally or regionally advanced disease, and those with recurrent and/or metastatic disease. Comorbidities (medical problems in addition to the diagnosed cancer) associated with tobacco and alcohol abuse can affect treatment outcome and the tolerability of aggressive treatment in a given patient.

[edit] Surgery for head and neck cancer

[edit] Radiation treatments of head and neck cancer

[edit] Toxicities of treatment

[edit] The role of chemotherapy in head and neck cancer

[edit] Induction chemotherapy

[edit] Concomitant chemoradiotherapy

[edit] Targeted therapy

Targeted therapy, according to the National Cancer Institute, is "a type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells without harming normal cells." Some targeted therapy used in squamous cell cancers of the head and neck include cetuximab, avastin, and erlotinib.

The best quality data are available for cetuximab since the 2006 publication of a randomized clinical trial comparing radiation treatment plus cetuximab versus radiation treatment alone^[18]. This study found that concurrent cetuximab and radiotherapy improves survival and locoregional disease control compared to radiotherapy alone, without a substantial increase in side effects, as would be expected with the concurrent chemoradiotherapy, which is the current gold standard treatment for advanced head and neck cancer. Whilst this study is of pivotal significance, interpretation is difficult since cetuximab-radiotherapy was not directly compared to chemoradiotherapy. The results of ongoing studies to clarify the role of cetuximab in this disease are awaited with interest.

Another study evaluated the impact of adding cetuximab to conventional chemotherapy (cisplatin) versus cisplatin alone. This study found no improvement in survival or disease-free survival with the addition of cetuximab to the conventional chemotherapy. ^[19]

Head and neck cancer clinical trials employing bevacizumab, an inhibitor of the angiogenesis receptor VEGF, are recruiting patients as of March, 2007. No published clinical trial information is available as of that date.

Erlotinib is an oral EGFR inhibitor, and was found in one Phase II clinical trial to retard disease progression. ^[20] Scientific evidence for the effectiveness of erlotinib is otherwise lacking to this point. A clinical trial evaluating the use of erlotinib in metastatic head and neck cancer is recruiting patients as of March, 2007.

[edit] Post-treatment outcome

[edit] Residual deficits

Even after successful definitive therapy, head and neck cancer patients face tremendous impacts on quality of life. Despite marked advances in reconstructive surgery and rehabilitation, intensity-modulated radiotherapy (IMRT) and conservation approaches to certain malignancies, some patients continue to have significant functional deficits.

[edit] Problem of second primaries

Survival advantages provided by new treatment modalities have been undermined by the significant percentage of patients cured of head and neck squamous cell carcinoma (HNSCC) who subsequently develop second primary tumors. The incidence of second primary tumors ranges in studies from 9.1% ^[21] to 23% ^[22] at 20 years. Second primary tumors are the major threat to long-term survival after successful therapy of early-stage HNSCC. Their high incidence results from the same carcinogenic exposure responsible for the initial primary process, called field cancerization.

[edit] References

^ Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun M. "Cancer statistics, 2006". CA Cancer J Clin 56 (2): 106-30. PMID 16514137.
^ Titcomb C (2001). "High incidence of nasopharyngeal carcinoma in Asia". J Insur Med 33 (3): 235-8. PMID 11558403.
^ {{cite journal |author=Gourin C, Podolsky R |title=Racial disparities in patients with head and neck squamous cell carcinoma |journal=Laryngoscope |volume=116 |issue=7 |pages=1093-106 |year=2006 |pmid=16826042
^ Spitz M (1994). "Epidemiology and risk factors for head and neck cancer". Semin Oncol 21 (3): 281-8. PMID 8209260.
^ Murata M, Takayama K, Choi B, Pak A (1996). "A nested case-control study on alcohol drinking, tobacco smoking, and cancer". Cancer Detect Prev 20 (6): 557-65. PMID 8939341.
^ Winn D. "Smokeless tobacco and aerodigestive tract cancers: recent research directions". Adv Exp Med Biol 320: 39-46. PMID 1442283.
^ Iribarren C, Tekawa I, Sidney S, Friedman G (1999). "Effect of cigar smoking on the risk of cardiovascular disease, chronic obstructive pulmonary disease, and cancer in men". N Engl J Med 340 (23): 1773-80. PMID 10362820.
^ Andre K, Schraub S, Mercier M, Bontemps P (1995). "Role of alcohol and tobacco in the aetiology of head and neck cancer: a case-control study in the Doubs region of France". Eur J Cancer B Oral Oncol 31B (5): 301-9. PMID 8704646.
^ Levi F, Pasche C, La Vecchia C, Lucchini F, Franceschi S, Monnier P (1998). "Food groups and risk of oral and pharyngeal cancer". Int J Cancer 77 (5): 705-9. PMID 9688303.
^ Liede K, Hietanen J, Saxen L, Haukka J, Timonen T, Häyrinen-Immonen R, Heinonen O (1998). "Long-term supplementation with alpha-tocopherol and beta-carotene and prevalence of oral mucosal lesions in smokers". Oral Dis 4 (2): 78-83. PMID 9680894.
^ Bairati I, Meyer F, Gélinas M, Fortin A, Nabid A, Brochet F, Mercier J, Têtu B, Harel F, Mâsse B, Vigneault E, Vass S, del Vecchio P, Roy J (2005). "A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients". J Natl Cancer Inst 97 (7): 481-8. PMID 15812073.
^ Jeng J, Chang M, Hahn L (2001). "Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives". Oral Oncol 37 (6): 477-92. PMID 11435174.
^ Pathmanathan R, Prasad U, Sadler R, Flynn K, Raab-Traub N (1995). "Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma". N Engl J Med 333 (11): 693-8. PMID 7637746.
^ Tune C, Liavaag P, Freeman J, van den Brekel M, Shpitzer T, Kerrebijn J, Payne D, Irish J, Ng R, Cheung R, Dosch H (1999). "Nasopharyngeal brush biopsies and detection of nasopharyngeal cancer in a high-risk population". J Natl Cancer Inst 91 (9): 796-800. PMID 10328111.
^ Gourin C, Podolsky R (2006). "Racial disparities in patients with head and neck squamous cell carcinoma". Laryngoscope 116 (7): 1093-106. PMID 16826042.
^ Iro H, Waldfahrer F (1998). "Evaluation of the newly updated TNM classification of head and neck carcinoma with data from 3247 patients". Cancer 83 (10): 2201-7. PMID 9827726.
^ Al-Sarraf M. "Treatment of locally advanced head and neck cancer: historical and critical review". Cancer Control 9 (5): 387-99. PMID 12410178.
^ Bonner J, Harari P, Giralt J, Azarnia N, Shin D, Cohen R, Jones C, Sur R, Raben D, Jassem J, Ove R, Kies M, Baselga J, Youssoufian H, Amellal N, Rowinsky E, Ang K (2006). "Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck". N Engl J Med 354 (6): 567-78. PMID 16467544.
^ Burtness B, Goldwasser M, Flood W, Mattar B, Forastiere A (2005). "Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study". J Clin Oncol 23 (34): 8646-54. PMID 16314626.
^ Soulieres D, Senzer N, Vokes E, Hidalgo M, Agarwala S, Siu L (2004). "Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck". J Clin Oncol 22 (1): 77-85. PMID 14701768.
^ Jones A, Morar P, Phillips D, Field J, Husband D, Helliwell T (1995). "Second primary tumors in patients with head and neck squamous cell carcinoma". Cancer 75 (6): 1343-53. PMID 7882285.
^ Cooper J, Pajak T, Rubin P, Tupchong L, Brady L, Leibel S, Laramore G, Marcial V, Davis L, Cox J (1989). "Second malignancies in patients who have head and neck cancer: incidence, effect on survival and implications based on the RTOG experience". Int J Radiat Oncol Biol Phys 17 (3): 449-56. PMID 2674073.

[edit] See also

oral cancer
cancer of the larynx
thyroid cancer
adenoid cystic carcinoma - a type of salivary gland cancer
Burkitt's lymphoma - a type of lymphoma that affects the head and neck
Dermatofibrosarcoma protuberans - a type of sarcoma that may involve the head and neck
Hodgkin's disease - a lymphoma that often involves the lymph nodes in the neck
paraganglioma - usually found in the head and neck region
skin cancers - may involve the head and neck
Bobby Hamilton - a NASCAR driver who died of head and neck cancer