Spanning a Spectrum of Issues Related to Head and Neck Cancers


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Five recent articles in JAMA Otolaryngology–Head & Neck Surgery1-5 span a spectrum of issues related to head and neck cancers. These include risk factors, concentration of care to teaching hospitals, avoiding venous thromboembolism, and encouraging patients to eat and do swallowing exercises to maximize chances of returning to a regular diet after treatment.

HPV Is a Major Risk Factor

More than 90% of head and neck surgeons responding to an online survey said that they discussed risk factors for head and neck cancer, and specifically human papillomavirus (HPV), with their patients.1

“The relationship of human papillomavirus to oropharyngeal carcinogenesis is now well established, with 40% to 80% of cases of oropharyngeal squamous cell carcinoma in the United States estimated to be related to HPV,” the authors stated. The incidence of oropharyngeal squamous cell carcinoma has also been increasing, “a trend now attributed to the HPV epidemic,” they added, rising 225% between 1988 and 2004 in the United States.

The survey was available online to all 1,081 members of the American Head and Neck Society and had an overall response rate of 27.5%. Most of those responding (80.4%) were fellowship-trained head and neck surgeons, and most (78.1%) practiced in the United States.

Less than 50% of survey respondents reported discussing the importance of the HPV vaccination for preadolescents. The most common reason for not mentioning it, selected from the survey list by 38.7% of respondents, was “Vaccine is not appropriate for most adults so my patients are not interested.” The next most common reason, chosen by 16.7%, was “Safety and effectiveness of vaccine are not yet proven.”

The article pointed out that there are two HPV vaccines licensed by the U.S. Food and Drug Administration, Gardasil and Cervarix, both effective against HPV type 16, as well as other types. The Centers for Disease Control and Prevention currently recommends routine HPV vaccination for girls and boys aged 11 to 12 years, but the three-shot series can be started as early as age 9. “Catch-up immunization is recommended to age 26 years for women and age 21 years for men,” the authors wrote. “With more than 90% of HPV-positive [oropharyngeal squamous cell carcinoma] attributable to HPV 16, it is possible that the HPV vaccination will have an impact on [prevention of the disease]; currently, however, there is no evidence that HPV vaccines are effective against oral HPV infection.”

Among survey respondents with daughters, 68.9% indicated that they intend to or have had their children vaccinated. For those with sons, the percentage was 55.8%. “This is in spite of the young average age of the respondents’ children, which would indicate that for many, vaccination would still be possible,” the authors noted.

Dental Caries Not a Risk Factor

An inverse relationship between dental caries and head and neck squamous cell carcinoma was “an unexpected finding” of a case control study involving 399 patients with newly diagnosed primary head and neck squamous cell carcinoma and 221 controls. The finding was unexpected, the investigators explained, “because dental caries has been considered a sign of poor oral health.”2

The study included all patients seen at the Roswell Park Cancer Institute Department of Dentistry and Maxillofacial Prosthetics between June 15, 1999, and September 14, 2007, except those who had a history of cancer, dysplasia, or immunodeficiency, or were younger than 21. Among the patients with head and neck squamous cell carcinoma, 37.8% had oropharyngeal squamous cell carcinoma, 36.6% had oral cavity squamous cell carcinoma, and 25.6% had laryngeal squamous cell carcinoma.

Compared to controls, patients with head and neck squamous cell carcinoma had a significantly lower mean number of teeth with caries, crowns, endodontic treatments, and fillings, but more missing teeth. After adjustment for age at diagnosis, sex, marital status, smoking status, and alcohol use, those in the upper third in the number of caries, crowns, and endodontic treatments were less likely to have head and neck squamous cell carcinoma than those in the lower third. “Missing teeth was no longer associated with [head and neck squamous cell carcinoma] after adjustment for confounding,” the researchers reported.

The inverse relationship between dental caries and head and neck squamous cell carcinoma persisted even among those who had never smoked and never drank alcohol. The association remained significant among patients with oral cavity and oropharyngeal squamous cell carcinoma but not among those with laryngeal squamous cell carcinoma.

Two other objective measures of long-standing caries history—endodontic treatments and crowns—were also inversely associated with head and neck squamous cell carcinoma. “This supports the validity of the association between dental caries and [head and neck squamous cell carcinoma], suggesting that it is not likely a chance finding,” the authors commented.

“Caries is a dental plaque-related disease. Lactic acid bacteria cause demineralization (caries) only when they are in dental plaque in immediate contact with the tooth surface. The presence of these otherwise beneficial bacteria in saliva or on mucosal surfaces may protect the host against chronic inflammatory diseases and [head and neck squamous cell carcinoma]. We could think of dental caries as a form of collateral damage and develop strategies to reduce its risk while preserving the beneficial effects of the lactic acid bacteria,” the study concluded.

Increasing Concentration of Care

“Head and neck oncologic care is increasingly being regionalized to teaching hospitals and academic centers,” concluded an analysis of all inpatient admissions with a primary head and neck cancer diagnosis contained within the Nationwide Inpatient Sample during the years 2000, 2005, and 2010.3

Over the years, “as expected, and in keeping with a slowly increasing aging population, there were an increasing number of inpatient hospital stays for head and neck cancer,” representing a percentage increase of approximately 29%, the investigators found. They also “found a relative concentration or ‘regionalization’ of inpatient head and neck cancer care evolving by the year 2010, such that almost 80% of inpatient cancer care occurred at teaching hospitals.”

The percentage of admissions to teaching hospitals rose from 61.7% in 2000 to 64.2% in 2005 to 79.8% in 2010, a statistically significant increase (P < .001). “Multivariate logistic regression analysis determined that the increase in proportion of cases at teaching hospitals over the calendar years of the study, particularly for the shift in proportion from 2005 to 2010, remained significant even when adjusting for hospital region, hospital bed size, and expected source of payment (P < .001),” the researchers reported.

The adjusted odds ratio for a head and neck cancer case being admitted to a teaching institution for 2005 vs 2000 was 1.1 (95% confidence interval [CI] = 0.7–1.7), compared with 2.5 (95% CI = 1.6–3.7) for a case being admitted to a teaching institution for 2010 vs 2000.

The percentage of cases in hospitals with a large number of beds also increased from 69.2% in 2000 to 71.4% in 2005 and 73.3% in 2010. The primary expected payer distribution did not change significantly over the study years, holding at about 39.6% for Medicare, 33.3% for private insurance, 17.4% for Medicaid, and 9.7% classified as other.

“On the positive side, regionalization of head and neck cancer care to teaching institutions is likely to offer significant individual patient and societal benefit, although such benefits will need to be confirmed over time,” the authors wrote. The benefits would come from the support staff, adjunct services, and familiarity with recovery for complex head and neck surgical procedures at teaching hospitals and anticipated improved quality and outcomes resulting from high volumes for less commonly performed procedures.

“However, this trend of concentration of care also compels us to reconsider the goals of basic otolaryngology–head and neck surgical training,” the authors stated. “The observed regionalization of complex head and neck cases logically requires revision of what constitutes the basic body of knowledge needed to certify the majority of trainees in otolaryngology vs the more specialized body of knowledge (a step below fellowship education) needed for more-focused, high-volume care.”

Risk of Venous Thromboembolism

Hospitalized patients not routinely receiving anticoagulation therapy following surgery for head and neck cancer are at increased risk of venous thromboembolism, according to results of a prospective study of 100 consecutive patients hospitalized at a tertiary care academic surgical center.4 Researchers measured new cases of venous thromboembolism within 30 days of surgery among patients hospitalized for at least 4 days. The overall incidence of venous thromboembolism was 13%, including 8 patients with clinically significant venous thromboembolism (7 with deep venous thrombosis and 1 with pulmonary embolism) and 5 with asymptomatic lower-extremity superficial venous thromboembolism detected on ultrasonographic evaluation alone.

“Of note, only 4 of the clinically significant [venous thromboembolisms] provoked any signs or symptoms. So it is likely that only these 4 (50%) would have been discovered in the absence of our rigorous prospective [venous thromboembolism] screening,” the researchers stated.

Among the 14% of patients who received some form of postoperative anticoagulation therapy, the rate of bleeding complications (30.1%) was higher than that in patients without anticoagulation therapy (5.6%, P = .01).

The mean age of the study participants was 63.5 years. Most participants had a history of smoking (73%) and had a diagnosis of squamous cell carcinoma (78%). “Participants underwent a variety of head and neck cancer surgical procedures, including 80% who had some form of microvascular reconstruction.” As expected, the investigators noted, these patients had moderate functional impairment and moderate to high risk for venous thromboembolism on risk assessment.

“Compliance with [venous thromboembolism] guidelines has historically been poor among otolaryngologists presumably because patients are often able to ambulate soon after surgery, and the potential consequences of airway compromise from bleeding or hematoma are catastrophic. Furthermore, there is relatively little data supporting the use of routine postoperative anticoagulation in head and neck surgery patients,” the investigators noted.

“Our results support the use of routine [venous thromboembolism] chemoprophylaxis in patients with head and neck cancer admitted for more than 72 hours after surgery,” the researchers concluded. “Importantly, these data establish a baseline [venous thromboembolism] rate in high-risk head and neck cancer surgery patients that can serve as a benchmark for future prospective trials of [venous thromboembolism] chemoprophylaxis and risk stratification.”

Eat and Exercise

Patients who eat and adhere to preventive swallowing exercises while being treated with radiotherapy or chemoradiotherapy for pharyngeal cancers “have the highest rate of return to a regular diet and the shortest duration of gastronomy dependence,” according to a retrospective observational study at The University of Texas MD Anderson Cancer Center in Houston.

The study included 497 patients treated with definitive radiotherapy or chemoradiotherapy for pharyngeal cancer. At the conclusion of that treatment, 74% maintained oral intake, 40% full and 34% partial, and 58% reported adherence to swallowing exercises.

Maintenance of oral intake during radiotherapy or chemoradiotherapy and swallowing exercise adherence “were independently associated with better long-term diet after [radiotherapy or chemoradiotherapy] (P = .045 and P < .001, respectively) and shorter duration of gastrostomy dependence (P < .001 and P = .007, respectively) in models adjusted for tumor and treatment burden,” the researchers reported.

“Swallowing is the top functional priority rated by patients with head and neck cancers before and after treatment and is a driver of quality of life in survivors,” the authors noted. “Proactive swallowing therapy is prescribed to provide maximal use of the swallowing mechanism during treatment. Two goals can be given to patients under a ‘use it or lose it’ paradigm: eat and exercise.”

The benefits of maintaining oral intake during radiotherapy and chemoradiotherapy and swallowing exercise adherence have been previously demonstrated, the authors continued, “but to our knowledge, the independent effects of these efforts have not been reported to date. In this study, we found that both swallowing goals—eat and exercise—were independently associated with significantly better swallowing-related end points,” they wrote.

“In addition, subgroup analyses suggested dose-dependent benefits. That is, these data imply that patients who either eat or exercise fare better than those who do neither, and swallowing end points are best among those who both eat and exercise,” they noted. ■

Disclosure: For full disclosures of the study authors, visit archotol.jamanetwork.com.

References

1. Malloy KM, Ellender SM, Goldenberg D, et al: A survey of current practices, attitudes, and knowledge regarding human papillomavirus-related cancers and vaccines among head and neck surgeons. JAMA Otolaryngol Head Neck Surg. August 29, 2013 (early release online).

2. Tezal M, Scannapieco FA, Wactawski-Wende J, et al: Dental caries and head and neck cancers. JAMA Otolaryngol Head Neck Surg. September 12, 2013 (early release online).

3. Bhattacharyya N, Abemayor E: Changing patterns of hospital utilization for head and neck cancer care: Implications for future care. JAMA Otolaryngol Head Neck Surg. September 12, 2013 (early release online).

4. Clayburgh DR, Stott W, Cordiero T, et al: Prospective study of venous thromboembolism in patients with head and neck cancer after surgery. JAMA Otolaryngol Head Neck Surg. September 26, 2013 (early release online).

5. Hutcheson KA, Bhayani MK, Beadle BM: Eat and exercise during radiotherapy or chemoradiotherapy for pharyngeal cancers: Use it or lose it. JAMA Otolaryngol Head Neck Surg. September 19, 2013 (early release online).



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