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JADA Specialty Scan - O & M Pathology
JADA Specialty Scan

Changes seen in oral cancer trends

Recent trends show a dramatic rise in the incidence of oropharyngeal squamous cell carcinoma (OP-SCC), with a marked increase in lesions related to human papillomavirus infection. Nevertheless, oral cavity squamous cell carcinoma (OC-SCC) remains the most common malignancy of the head and neck. Although the oral cavity and oral pharynx are separate regions that border each other yet do not overlap, the tumors are often reported about in aggregate with other pharyngeal or head and neck malignancies. Anatomic subsite definitions are sometimes unclear or may not enable distinction between the oral cavity and the oropharynx.

Recognizing evidence supporting that tumors at these two sites are distinct and unique, with differing development and causes, treatment and prognosis, a team of scientists at the University of South Carolina, Charleston, reviewed the latest evidence on OC-SCC and OP-SCC, particularly comparing and contrasting tumors at both sites with respect to epidemiology, etiology, risk factors, early diagnosis and treatment. The research, updating a review in 2002, was published July 27 in the online edition of CA: A Cancer Journal for Clinicians.

Authors defined the oral cavity as including the labial mucosa, buccal mucosa, floor of the mouth, alveolar ridge and gingiva, anterior two-thirds of the tongue, hard palate and retromolar trigone. They outlined that the oropharynx consists of the soft palate, base of tongue, palatine tonsils, palatoglossal folds, valleculae and posterior pharyngeal wall.

Although many regions have reported decreasing or stabilizing trends for OC-SCC, others have exhibited markedly increasing trends. Authors said significant epidemiologic shifts can be accounted for as they seem to reflect dynamic risk factor trends. The traditional modifiable risk factors include tobacco and alcohol use.

However, over the past several decades, human papillomavirus (HPV) has emerged as a major etiologic factor for OP-SCC. The authors note evidence showing that in regions such as North America, Australia and parts of Europe, a dramatic increase in HPV-positive tumors accounts for rising OP-SCC incidence. In contrast, regional variations in trends for OC-SCC and HPV-negative OP-SCC are largely consistent with tobacco use trends, a traditional major risk factor. The majority of HPV-related head and neck squamous cell cancer arises in the oropharynx, particularly the palatine and lingual tonsils. In contrast, only a small proportion of squamous cell cancers in the oral cavity appear to be caused by HPV.

“Interestingly, the prevalence of high-risk HPV DNA in oropharyngeal and oral cancers appears to vary by geographic region,” researchers reported. For OP-SCC, prevalence has been reported to be highest (approximately 60 percent) in North America; intermediate (approximately 36 percent to 45 percent) in Asia, Oceana and Europe; and low (approximately 15 percent) in South and Central America.

“Remarkably, in the United States, HPV has been estimated to account for approximately 16 percent of OP-SCCs in the early 1980s compared with >60 percent of cases in more recent studies,” authors reported. They also noted that the risk profile for HPV-positive oropharyngeal carcinomas differs from that for HPV-negative tumors. Although there is a male predilection in both, HPV OP-SCCs are more likely to occur in patients who are white, somewhat younger (median age, 54 years vs. 58 years for HPV-negative OP-SCCs) and of higher socioeconomic status. HPV-positive OP-SCC also is also strongly associated with an increased number of lifetime sexual or oral sexual partners. Authors said more research is needed to clarify interactions between HPV, tobacco and alcohol,

The availability of vaccines targeting high-risk HPV subtypes offers great promise in controlling the rise of OP-SCC in the future, authors surmised based on their assessment of the results from a clinical trial in Costa Rica. The study reported high rates of vaccine efficacy against two types of HPV oral infection four years after vaccination. “However, prevention of OP-SCC is not yet an approved indication for HPV vaccination, and further studies are ongoing,” authors said. “In addition, there is a need to address barriers to vaccination.”

Authors reviewed variations in the incidence, mortality and risk factors of both types of squamous cell cancers from the body of literature, including unclear evidence as to the underlying cause for the increased tongue cancer in the U.S. and other regions. “In particular, a surprising increase in oral tongue cancer has been observed in young females, often with no significant tobacco and alcohol exposure,” authors noted. The vast majority of tongue cancers examined thus far have been negative for high risk HPV. According to SEER data (Surveillance, Epidemiology, End Results), from 2000 through 2012, the incidence of tongue cancer in adults aged 20 to 44 years increased among females but decreased among males in the United States. A pooled analysis of case control studies by the International Head and Neck Cancer Epidemiology Consortium showed adults aged 45 years and younger exhibited a higher proportion of oral tongue cancers compared with adults older than 45 years. Also in that study, the associations of smoking and drinking with oral cavity cancer were weaker in young adults compared with older adults.

A major risk factor for both OC-SCC and OP-SCC continues to be tobacco and alcohol consumption, with combined cigarette smoking and alcohol consumption exhibiting a synergistic effect, increasing relative risk for head and neck squamous cell carcinoma. Multicenter studies in Europe and Asia and pooled analysis of European and American case control studies show that more than half of oral cavity and oropharyngeal cancer cases are attributed to tobacco and/or alcohol. Betel quid chewing — a common practice in many parts of Asia, particularly Southeast Asia, as well as in migrant Asian communities around the world — boosts the risk for OC-SCC drastically. In Southeast Asia, 75 percent of males affected by oral cancer have a history of combined smoking-drinking-betel quid exposure.

Among conclusions authors said it is important for clinicians to be aware of the differences between oral cavity and oropharynx head and neck cancers so that appropriate patient education and multidisciplinary care can be provided to optimize outcomes. They asserted: “HPV vaccines may have the greatest potential to reduce the morbidity and mortality from OP-SCC, which has been increasing in incidence in the United States and other developed nations.”

Read the original article.


Consulting Editor: Paul C. Edwards MSc, DDS, FRCD(C)
Editor, American Academy of Oral and Maxillofacial Pathology
Professor, Dept. of Oral Pathology, Medicine, Radiology
Indiana University School of Dentistry

Associate Consulting Editor: Lynn W. Solomon DDS, MS
Chair, Research and Scientific Affairs Committee,
American Academy of Oral and Maxillofacial Pathology
Associate Professor, Dept. of Oral Diagnostic Sciences,
Nova Southeastern University College of Dental Medicine

E-cigarette use may hinder college student smokers from quitting

As use of electronic cigarettes continues to climb, especially among youth and young adults, researchers at Wake Forest (N.C.) School of Medicine sought to determine whether there was a relationship between e-cigarette use and smoking cessation in a sample of college student smokers. They published their findings in the August 2015 issue of the American Journal of Public Health.

Researchers studied students from seven colleges in North Carolina and four in Virginia, between the fall of 2010 and the fall of 2013, using one baseline survey and five follow-up surveys. Participants chosen from the Smokeless Tobacco Use in College Students study were first-year college students who were current smokers and reported no history of e-cigarette use in the initial survey. The baseline survey was conducted in their first fall semester, and five follow-up surveys were conducted each semester through the fall of their senior year.

Researchers invited 4,902 eligible students to participate in the longitudinal cohort study and 3,146 (64.2 percent) completed the baseline survey. Of this group, 669 (21.3%) were current cigarette smokers with no history of e-cigarette use at baseline. Follow-up surveys had a retention rate between 78.2 percent and 80.1 percent. Researchers’ surveys measured demographics (gender, race, ethnicity and mother’s educational level), membership in Greek letter organizations, tobacco use (smoking and smoking frequency) and e-cigarette use.

At wave 6 — the final survey — researchers also questioned participants on lifetime use of smokeless tobacco, including chew, dip, snus, hookah tobacco, little cigars, cigarillos and large cigars; exposure to peers’ smoking and family smoking; and reasons for e-cigarette use.

The authors examined the variables associated with trying an e-cigarette between baseline and wave 5. Of the 669 participants who were smokers at baseline with no history of e-cigarette use, researchers excluded 73 participants who first tried an e-cigarette between wave 5 and wave 6 and 15 participants who were not current smokers when they first tried e-cigarettes. Of the remaining participants, 323 individuals had sufficient data to determine whether they had tried an e-cigarette while being a current smoker and the researchers studied an analytic sample of 271 participants. Most participants were considered by researchers to be “occasional” smokers.

Just over half (51.7 percent) of participants were female and most were White (89.7 percent) and non-Hispanic (94.1 percent). Nearly 60 percent had a mother with a college degree or higher and less than a quarter had joined a Greek letter organization by wave 6. The percentage of participants who tried an e-cigarette between wave 2 and wave 5 increased from 13.3 percent to 43.5 percent. Those who tried e-cigarettes were less likely to have a mother with a college or higher degree and more likely to smoke cigarettes on more days at baseline, have tried more tobacco products in their lifetime and have family members and friends that smoke.

At wave 6, participants’ responses on why they tried e-cigarettes included curiosity (91.6 percent), having friends that used them (70.2 percent) and believing they were safer than cigarettes (69.9 percent). About half responded that they tried them because they cause less odor and could be used where smoking was not allowed and 31 percent said they used them to cut down on smoking. Only 20.2 percent responded that they tried e-cigarettes to help with smoking cessation.

The authors noted that e-cigarette use in the college student population may be associated more with novelty seeking than as a cessation aide. They also say the data show that not only did using e-cigarettes not deter cigarette smoking, e-cigarettes may have contributed to continued smoking. They called for more research to determine whether continued, higher e-cigarette use, defined as using daily for at least 1 month, is associated with higher rates of smoking cessation among college students.

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Update on major salivary gland cancers

Noting a dearth of prospective evidence regarding cancer of the major salivary glands, a team of scientists conducted a review of contemporary patterns of relapse and prognostic factors for such cancers and published their findings in the August 2015 issue of Oral Oncology.

The relative scarcity and diverse biology of malignancies of the major salivary glands — parotid, submandibular and sublingual — have made progress in their management challenging, according to the authors. Unlike other head and neck cancers, outcomes in salivary cancer have not improved appreciably over time. “Unfortunately, patient heterogeneity and paucity have precluded prospective, randomized trials that could guide us in the integration of systemic therapy into the therapeutic armamentarium, and we must rely on retrospective data,” they said.

The team sought to report on relevant current standards of practice, focusing on prognostic factors for disease recurrence and overall patterns of recurrence within a modern cohort of patients.

To investigate, scientists obtained the records of 112 consecutive patients over the age of 18 who underwent surgical resection for malignancies of the major salivary glands at Emory University, in Atlanta, between January 1997 and September 2010. All patients had primary surgery as their initial treatment. Adjuvant chemotherapy and radiation was dictated at the discretion of the treating physicians and the decision to give that therapy was generally driven by high risk factors — close or positive margins, T3-T4 tumor, perineural invasion, high grade and/or positive lymph nodes. The median follow-up was 55.1 months.

Among results, the median age at diagnosis was 56 years. Adenocarcinoma was the most common histology encountered. Clinical nerve involvement was most common in adenocarcinomas. Patients with clinical nerve involvement were more likely to have high-grade disease. There was no association between histology and the presence of close or positive margins following resection.

Rates of locoregional control at five years were 94.6 percent and 60.4 percent for stages I/II and III/IV respectively. Deep parotid location, male gender, lymph node dissection, facial nerve involvement, advanced T stage, nodal involvement, stage III/V high tumor grade, extracapular extension, adjuvant chemotherapy, positive margin lymphovascular space invasion, older age and larger tumor size was associated with lesser locoregional control. “Notably, close margin (<5mm), perineural invasion and bone invasion were not associated with LRR [locoregional recurrence],” authors said. Clinical nerve involvements, age at diagnosis and tumor size were significant predictors of LRR in all patients.

“The findings in our contemporary series, which spans a relatively short treatment period, closely follow the studies that precede it regardless of era,” authors said in discussion. “Overall survival at five years in our series was 74.7 percent. Overall rates of distant and locoregional control are similar to previously published series at 79 percent and 82.6 percent respectively. Survival following distant recurrence is exceedingly poor.”

Authors believe their findings to be the first to identify sublingual primary and deep parotid lobe involvement as a predictor of distant metastasis. In their discussion, they noted that one of the most significant advancements of the past decades in management of head and neck cancer has been the adoption of concurrent chemotherapy in both the definitive and postoperative settings.

Authors referred to a present-day examination of the role of concurrent chemotherapy in the setting of high-risk salivary gland cancer: A Randomized Phase II Study of Adjuvant Concurrent Radiation and Chemotherapy vs. Radiation Alone in Resected High-Risk Malignant Salivary Gland Tumors. “The results of this trial will hopefully elucidate the role of concurrent chemotherapy in high-risk patients,” authors said.

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Salivary stone risks examined

Salivary stones, affecting between 1 in 15,000 and 1 in 30,000 individuals, occur most commonly in both men and women over 40 years old, and are primarily located in the submandibular gland. These calcified structures can partially or totally obstruct the ductal system leading to recurrent swelling of the salivary gland, pain and acute or chronic infection. The causes and risk factors predisposing to salivary stone development are unclear.

In a study published in the May 2015 issue of Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Danish researchers sought to identify possible relationships between the presence of salivary stones and systemic diseases, medication, smoking and alcohol consumption.

The scientists conducted a retrospective case control study of patients who had salivary stones surgically removed at three hospitals in the Netherlands from November 2001 through December 2013. A total of 208 patients with salivary stones (112 males and 96 females) with a mean age of 46.8 years (age range 8-87 years) were compared with a control group of 208 sex- and age-matched patients (112 males and 96 females) with a mean age of 46.4 years (age range 8-88 years). The submandibular gland was involved in 85.6 percent of patients; the parotid in 9.6 percent and the sublingual in 2.4 percent.

Researchers found no relationship between salivary stone formation and systemic diseases, including endocrine, cardiovascular, infectious, internal, neurologic, rheumatologic and malignant diseases. Patients with salivary stones used significantly more antibiotics compared with controls and the authors theorize that this result may be due to a relationship between salivary stone formation and sialadenitis, for which a referring dentist or physician may have prescribed antibiotics as initial treatment. They did not observe significant differences for other types of medication. They also found no correlation between salivary stone formation, smoking and alcohol consumption.

In conclusion, the authors said the data “indicate that systemic diseases and use of medication do not play a prominent role in the development of salivary stones. This suggest that local factors, such as anatomic variations of the salivary ducts, an altered biochemical composition of saliva or both are probably more important factors in the development of salivary stones.”

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Mark your calendar for 2016 annual meeting

Please join us for the American Academy of Oral and Maxillofacial Pathology Annual Meeting at the Westin Cincinnati, May 21-25, 2016.

Registrants are also invited to join the AAOMP for a rare opportunity to learn from some of the world's leading oral and maxillofacial pathologists on Friday, May 20, 2016, at the Westin Cincinnati.

Watch for more information.


What is Specialty Scan?

This is one in a series of quarterly newsletters updating dentists on selected specialties in dentistry. Information presented is aggregated and summarized from previously published materials, each item attributed to its publication of origin. This issue of JADA Specialty Scan focuses on oral pathology, the third in the series on this topic for 2015. Other Specialty Scan issues are devoted to endodontics, oral and maxillofacial radiology, orthodontics, pediatric dentistry, periodontics and prosthodontics. The ADA has engaged the specialty organizations in these areas as well as its own Science Institute and Division of Legal Affairs to assist with these newsletters. We welcome feedback on this and all Specialty Scan issues.

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