Cancer (Head and Neck)

Squamous cell carcinomas of the head and neck collectively refer to cancers arising from the squamous cell layer of the mucosal surfaces in the oral cavity and oropharynx.¹ Head and neck cancers can also begin in the salivary glands, paranasal sinuses or nasal cavity, but are relatively uncommon.¹ Although they border each other, the oral cavity (OC) and oropharynx (OP) are separate, non-overlapping anatomic regions (Table; Figure).^{2, 3}

Table. Anatomic Distinctions Between the Oral Cavity and the Oropharynx

Diagram of the oral cavity and oropharynx from the Centers for Disease Control and Prevention

Squamous cell carcinoma (SCC) is the most common malignancy in the OC and pharynx, accounting for 90% of cancers of the head and neck, after excluding non-melanoma skin cancers.² The American Cancer Society’s estimated number of new OC and pharynx cancer cases in the U.S. in 2022 is 54,000, while the estimated number of deaths from oral cavity and pharyngeal cancers in 2022 is 11,230.⁴ These estimates account for 2.8% of all cancers diagnosed and 1.8% of all cancer deaths, with over twice the number of new oral cavity and pharyngeal cancer cases and cancer deaths projected to occur in men than in women.⁴

Data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program indicate that, from 2009 to 2018, there was a statistically significant annual percentage increase in the incidence of squamous cell carcinoma of the tongue (1.5%), tonsil (1.7%) and oropharynx (4.2%); and a decrease in the annual percent change in incidence of cancer of the lip (down 1.9%), floor of the mouth  (down 3.8%) and hypopharynx (down 2.7%).⁵

According to a 2022 study, the most common subsite of OC-SCC in the U.S. is the tongue (41.7%), and the overall incidence of oral tongue SCC has steadily increased among American men and women of all ages, with an average annual percentage increase of 1.8%.⁶ The 5-year relative survival rate for those with localized oral cavity or pharynx cancer at diagnosis is 85%, compared with only 40% in patients whose cancer has metastasized.⁷

The major risk factors for OC-SCC and OP-SCC are tobacco use,^{2, 8-10} alcohol consumption,^{2, 8, 11-14} interaction between heavy use of tobacco and alcohol together,^{15, 16} and chewing betel quid (“paan,” often practiced in Asian, migrant Asian, and other communities).²  Human papillomavirus (HPV) infection is a major risk factor for oropharyngeal cancer and is also a risk factor for a small percentage of cancers at other anatomic sites of the head and neck (see following section “Focus on HPV in Oropharyngeal Cancer”).^{2, 17-21} A 2016 study reported that nearly 37 percent of oral cavity and pharyngeal cancer cases are attributable to alcohol consumption, with higher risks reported among moderate to heavy drinkers of alcohol.²²

Ultraviolet exposure may be the likely risk factor associated with SCC of the lip.²³ In the United States, male adults in older age groups have been reported to have increased risk of OC/OP-SCC.²⁴ Smoking-associated risk appears to be dose dependent and correlates with daily or cumulative cigarette consumption.² For patients who quit smoking, the risk for OC-SCC and OP-SCC declines over time and may approach that of nonsmokers after 10 or more years of cessation.^{2, 10, 25} The risk of head and neck cancer 20 or more years following cessation of alcohol consumption appears to approach the risk of those who have never consumed alcohol.²⁶

Oncogenic oral HPV infection (especially HPV-16) has been established as an etiologic risk factor for HPV-positive oropharyngeal cancer.^{2, 17, 18, 27} In the U.S., approximately 3.5 percent of adults have been estimated to have oncogenic oral HPV infection, and the prevalence of this type of infection was most prevalent among adult men who currently smoked and men who reported a greater number of lifetime oral sexual partners.^{28, 29}

Researchers have reported an increasing incidence of oral tongue SCC in the United States³⁰ and globally,³¹ including a 2.3% increase of oral tongue SCC among women.⁶ The reported increase in oral tongue SCC has been suggested to have a different causative mechanism (e.g., genetic abnormalities such as Fanconi anemia, other oncogenic viral infections, or other environmental exposures).³² There is also an increased risk for OC/OP-SCC in patients with certain rare heritable conditions, including Fanconi anemia, dyskeratosis congenita, and Bloom syndrome.^{2 33}

The HPV vaccine was developed to prevent cervical and other cancers of the reproductive system. The vaccine protects against the types of HPV that can cause oropharyngeal cancers, so it may also prevent oropharyngeal cancers; however, studies have not been done to show this.³⁴

Oncogenic oral HPV infection is a major risk factor for oropharyngeal cancer, rather than oral cancer, per se.^{2, 17, 18, 27, 35, 36}  HPV has emerged as an etiologic factor for OP-SCC of the tonsil and oropharynx,^{18, 35, 37} but not for the totality of tongue cancers.^{38, 39}  Based on data from U.S. cancer registries, an estimated 71% of OP-SCC each year—or over 11,000 cases—are associated with HPV infection.^{40, 41} The vast majority (over 90%) of HPV-positive OP-SCC are associated with HPV-16, a high-risk, HPV subtype that is commonly associated with cervical cancer and other anogenital cancers.^{18, 37, 42, 43}

Oropharyngeal cancer is now considered the most common cancer caused by HPV in the United States, with nearly 81 percent of OP-SCC cases classified as HPV-associated (between 2007 and 2015).⁴⁴ Three analyses of U.S. cancer databases over two time periods (2013-2014 and 2017-2018) indicated that white, non-Hispanic men have higher incidences of oral cavity and pharyngeal cancers in the U.S.^{21, 45, 46} Another study found that the median age of individuals diagnosed with HPV-associated OP-SCC in the U.S. has increased to about 58 years of age, with a growing number of cases across all age groups, including older adults.⁴⁷

Data suggest that oral HPV infection prevalence is lower in men and women who have received HPV vaccination than those who have not.⁴⁸ Although it is possible that the HPV vaccine might also ultimately prevent OP cancers, as the vaccine prevents an initial infection with HPV types that can cause these cancers, current data are lacking regarding prevention of HPV-associated OP cancer.³⁴ Clinical trials designed to answer these questions are currently underway.

HPV Vaccine

In 2020, the American Academy of Pediatric Dentistry (AAPD) issued an updated policy statement on HPV vaccination⁴⁹  as follows:

The AAPD supports measures that prevent [oral and oropharyngeal cancers], including the prevention of HPV infection, a critical factor in the development of oral squamous cell carcinoma.

The AAPD encourages oral health care providers to:

• Educate patients, parents, and guardians on the serious health consequences of [oral and oropharyngeal cancers] and the relationship of HPV to [oral and oropharyngeal cancers].
• Counsel patients, parents, and guardians regarding the HPV vaccination, in accordance with CDC recommendations, as part of anticipatory guidance for adolescent patients. 

In October 2018, the U.S. Food and Drug Administration (FDA) approved a supplemental application for Gardasil 9^® (HPV 9 valent-vaccine, recombinant; Merck & Co., Inc.) expanding the approved use of the vaccine to include women and men aged 27 through 45 years.⁵⁰ Gardasil 9^® was previously approved for use in males and females aged 9 through 26 years.

Two oral lesions that could be precursors to cancer are leukoplakia (white patches) and erythroplakia (red patches).^{2, 52} Although there is a known potential for malignant transformation, the majority of leukoplakias will not progress to cancer.²  Some oral lesions will show a combination of red and white features, termed erythroleukoplakia, speckled leukoplakia, or speckled erythroplakia.² Although less common than leukoplakia, erythroplakia and lesions with erythroplakic components have a much greater potential for becoming cancerous.⁵²

Because these white and/or red mucosal patches have an increased risk of becoming or already harboring invasive carcinoma, they have collectively been classified as “oral potentially malignant disorders.”³³ Any white or red patch/lesion that does not resolve in two weeks should be reevaluated and considered for biopsy to obtain a definitive diagnosis. ⁵²

Other possible signs and symptoms of head and neck cancers that patients may report include: ⁵²

• a lump or thickening in the oral soft tissues
• soreness or a feeling that something is caught in the throat
• difficulty chewing or swallowing
• ear pain
• difficulty moving the jaw or tongue
• hoarseness
• numbness of the tongue or other areas of the mouth
• swelling of the jaw that causes dentures to fit poorly or become uncomfortable

Signs and symptoms that persist for two weeks or more merit further investigation, such as a biopsy or referral to a specialist.⁵²

OP-SCC develops primarily in the palatine tonsils and base of the tongue, often appearing as an ulcerated mass, fullness, or irregular erythematous mucosal change.^{2, 53} OP-SCC tumors are thought to present at a more advanced stage than OC-SCC because of their ability to grow undetected (i.e., without overt symptoms) and their propensity for metastasis.² The most common chief complaints are presence of a neck mass (from metastatic disease), sore throat, and dysphagia.²

In 2017, an expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs published a systematic review/meta-analysis and guideline titled "Evidence-Based Clinical Practice Guideline for the Evaluation of Potentially Malignant Disorders in the Oral Cavity.”^{54, 55} The goal of this clinical practice guideline is to inform clinicians about the potential use of adjuncts as triage tools for the evaluation of lesions, including potentially malignant disorders, in the oral cavity. Among the guideline's recommendations:

• Clinicians should obtain an updated medical, social, and dental history and perform an intraoral and extraoral conventional visual and tactile examination in all adult patients.
• For patients with suspicious lesions, clinicians should immediately perform a biopsy of the lesion or refer the patient to a specialist.
• Salivary and light-based adjuncts are not recommended for evaluating lesions for malignancy. 

The U.S. Preventive Services Task Force (USPSTF)⁵⁶ concluded in 2013 that “current evidence is insufficient to assess the balance of benefits and harms of screening for oral cancer in asymptomatic adults,” although the statement specifically clarifies that, “This recommendation is intended for primary care providers and does not pertain to dental providers or otolaryngologists. Dental care providers and otolaryngologists may conduct a comprehensive examination of the oral cavity and pharynx during the clinical encounter.”

ADA Current Dental Terminology (CDT) code D0120 for “periodic oral evaluation” (established patient) includes “an oral cancer evaluation … where indicated.” CDT code D0150 for “comprehensive oral evaluation” (new or established patient) also includes “an evaluation for oral cancer where indicated.”

The National Institute for Dental and Craniofacial Research (NIDCR)⁵² provides a protocol for dental practitioners for an oral cancer examination based on the standardized oral examination method recommended by the World Health Organization. The NIDCR examination method is “consistent with those followed by the Centers for Disease Control and Prevention and the National Institutes of Health,” and requires adequate lighting, a dental mouth mirror, two 2" x 2" gauze squares, and gloves, and should take approximately 5 minutes.⁵² The NIDCR provides the examination protocol in poster form and also has a pamphlet on oral cancer for patients and a patient education resource for oral cancer and the oral cancer exam; these items are not copyrighted and can be reproduced freely. An additional resource is the video posted by the ADA demonstrating the evaluation of a patient for potentially malignant disorders, showing inspection and palpation elements of the intra- and extraoral examination.

The NIDCR⁵² suggests that a thorough head and neck examination should be a routine part of each patient's dental visit, as follows. Clinicians should be particularly vigilant in checking those who use tobacco or excessive amounts of alcohol.

• Examine your patients using the head and neck examination protocol described by the NIDCR.
• Take a history of their alcohol and tobacco use.
• Inform your patients of the association between tobacco use, alcohol use, and oral cancer.
• Follow-up to make sure a definitive diagnosis is obtained on any possible signs or symptoms of oral cancer.

A 2019 ADA Policy on “Early Detection and Prevention of Oral and Oropharyngeal Cancer” supports prevention education and routine visual and tactile examinations for all patients.⁵⁷

Given that mortality rates from OC/OP-SCC have been fairly stable,²⁴ it has been posited that earlier detection of oral cancers will improve prognosis.  A 2015 systematic review and meta-analysis by Seoane et al.⁵⁸ found that a longer time interval from a patient’s first symptom to referral for diagnosis was a “risk factor for advanced stage and mortality of oral cancer.”

A number of adjuncts to the standard clinical examination have been developed and are intended to improve disease detection. These include oral brush cytology, toluidine blue staining, and light-based detection systems to increase the visibility of oral mucosal lesions or provide real-time data on suspicious mucosal lesions.⁵⁹ Diagnostic performance in clinical studies has been inconsistent because results vary according to study settings and the sample populations enrolled.^{59, 60} As noted in the 2017 ADA clinical practice guideline and systematic review,^{54, 55} it is not yet clear whether these ancillary tests are helpful in triaging which patients need diagnostic or therapeutic follow-up, in part because these tests can also yield false-positive results. Diagnostic adjuncts have been evaluated primarily in referral clinic settings or cancer centers and in patients at high baseline risk of disease.⁵⁹ Data from studies in general clinic settings and in patients at low baseline risk of disease are more limited, and additional data are needed to characterize test performance in these populations and settings.⁵⁹

EARLY DETECTION AND PREVENTION OF ORAL AND OROPHARYNGEAL CANCER
(Trans.2019:277)

Resolved, that the American Dental Association recognizes that early oral and oropharyngeal cancer diagnosis has the potential to have a significant impact on treatment decisions and outcomes, and supports routine visual and tactile examinations for all patients, and be it further

Resolved, that the Association supports state and local Association-sponsored education activities to promote the prevention and early detection of oral and oropharyngeal cancer.

American Dental Association
Adopted 2019

HUMAN PAPILLOMAVIRUS (HPV) VACCINATION FOR THE PREVENTION OF INFECTION WITH HPV TYPES ASSOCIATED WITH OROPHARYNGEAL CANCER 
(Trans.2018:351)

Resolved, that the American Dental Association (ADA) adopts the position that HPV vaccination, as recommended by the CDC Advisory Committee on Immunization Practices, is a safe and effective intervention to decrease the burden of oral and oropharyngeal HPV infection; and be it further

Resolved, that the ADA urges dentists, as well as local and state dental societies, to support the use and administration of the HPV vaccine as recommended by the CDC Advisory Committee on Immunization Practices; and

Resolved, that the ADA encourages appropriate external agencies to support research to improve understanding of the natural history of oral HPV infection, transmission risks, screening and testing.

American Dental Association
Adopted 2018

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Guidelines and Additional Clinician Resources:
Evaluation of Potentially Malignant Disorders in the Oral Cavity

• Clinical Recommendations
  
• Systematic Review
  
• Chairside Guide
• Instructional Video

Patient Education:

Reducing the Risk of Oral Cancer (JADA For the Patient Page 2020)

Oral cancer: What to do if something unusual shows up? (JADA For the Patient Page 2017)

Additional ADA Resources:

• Search JADA for articles related to oral or oropharyngeal cancer
• ADA Clinical Evaluators Panel Survey: Human Papillomavirus Vaccine (2020)

ADA Store:

• The ADA Practical Guide to Soft Tissue Oral Disease (Item #P033)

ADA CE Online: HPV Infection, Risk Factors, and HPV-Related Oropharyngeal Cancer

American Cancer Society:

• HPV (Human Papillomavirus)
• Cancer Prevention Through HPV Vaccination: An Action Guide for Dental Health Care Providers (National HPV Vaccination Roundtable)

American Academy of Pediatrics:

• Immunizations
• Oropharyngeal Cancer and HPV Prevention in Children: 5 Key Points that Dental Professionals Need to Know

Centers for Disease Control and Prevention resources:

• Head and neck cancers
• 5 Ways to Boost Your HPV Vaccination Rates
• Human papillomavirus resources for parents and public, healthcare professionals, and partners and programs
• HPV vaccination: What can we do to bring specific partners to the table?
• Promotional flyers and posters regarding HPV vaccination for preteens and teens
• Vaccine “fact sheets” for preteens and teens (including HPV)

National Cancer Institute:  Head and Neck Cancer Fact Sheet

U.S. Department of Health and Human Services:  HPV Vaccine