O & M PathologyJADA Specialty Scan

Inherited factors linked to young adult head and neck cancers

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Some 550,000 new cases of head and neck cancer (HNC) are diagnosed annually worldwide and data shows increased incidence of head and neck neoplasms among young adults. Research published in the International Journal of Epidemiology sought to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients.

Scientists pooled data from 25 case-control studies from the International Head and Neck Cancer Epidemiology (INHANCE) consortium of young adults (45 years of age or younger) and older adults (over 45 years of age). They reviewed 2,010 cases and 4,042 controls in young adults and 17,700 cases and 22,704 controls in older adults and surveyed participants on their history of cigarette smoking, alcohol drinking, diet and family history of cancer.

“To our knowledge, this is the largest study to evaluate the role of the major risk factors for HNC in young adults as well as to compare risks in younger and older patients,” said Tatiana Natasha Toporcov, DDS, PhD, professor, Department of Epidemiology, University of São Paulo School of Public Health, the corresponding author for the study. “The large sample size allowed us to elucidate any differences in the role of risk factors in HNC in young adults according to age group, sex and cancer sub sites.”

Researchers found a higher proportion of oral cavity cancer (especially oral tongue cancer) among the young cases and this proportion was higher among women. They also found that the attributable fraction, or AF, (an estimated proportion of cases which could be avoided if exposures were eliminated) for smoking on the risk of HNC was 20% in young women, 49% in older women, 46% in young men and 64% in older men. The AF for drinking alcohol on the risk of HNC was 5% in young women, 20% in older women, 22% in young men, and 50% in older men. Data showed that eating a diet rich in fruits and vegetables was inversely associated with the risk of HNC in both age groups.

Family history of early-onset cancer was associated with HNC risk only in young adults. The AF for family history of early onset cancer on the risk of HNC was 23% in young adults and 2% in older adults.

"Although they were less likely to be drinkers and/or smokers, alcohol consumption was a risk factor for HNC in young adults,” said Dr. Toporcov. “However, a stronger association with heavy drinking was observed for the older group. Our results also indicate that the inverse association with fruit and vegetable intake is similar among young and older populations. Also, early onset cancer in the family was associated with HNC risk only among young adults.”

Authors say the key messages from the study results include:

“Our results support public health efforts to decrease exposure to major risk factors for HNC in the population regardless of age,” Dr. Toporcov concluded. “However, investigations of the role of other risk factors, such as human papilloma virus and inherited characteristics, on HNC in the younger age group are warranted.”



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


Associate Consulting Editor: Yi-Shing Lisa Cheng, DDS, MS, PhD
Associate Professor, Diagnostic Sciences,
TAMU-Baylor College of Dentistry

Sitafloxacin to treat bisphosphonate-related osteonecrosis of the jaw

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Although American and Japanese dental and health organizations have offered treatment recommendations for bisphosphonate-related osteonecrosis of the jaw (BRONJ), no standard therapy guidelines exist.

In this preliminary study, Japanese researchers sough to establish a treatment approach in which all patients with BRONJ, characterized by exposed, infected bone or intraoral/extraoral fistulas, were treated with sitafloxacin (STFX). Their study was published online in December 2014 in the journal Bone.

Scientists studied 20 BRONJ patients at the Department of Otorhinolaryngology and Oral Surgery, Kyorin Hospital, Tokyo, Japan, between April 2010 and April 2013. Fourteen had an underlying history of cancer, four had primary osteoporosis and two had glucocorticoid-induced osteoporosis.

For this study, scientists used a modified working definition of BRONJ: a greater than 1-month history of severe jaw pain, discharge of pus and current or previous treatment with a bisphosphonate in patients who presented with or without necrotic bone exposure. They excluded patients who exhibited no sign of infection.

The study included 16 patients with BRONJ who had not responded to 1-4 weeks of treatment with common antibiotics prescribed by outside clinicians, and 2 patients who developed BRONJ despite prophylactic treatment with common antibiotics following tooth extraction. Researchers isolated each potentially causative organism from pus collected from an intraoral or extraoral fistula in 10 patients on their first visit, rapidly identified these isolates and performed antimicrobial susceptibility testing of the isolated bacteria to sitafloxacin and the other antimicrobial agents.

They reevaluated patients’ lesions every other week to determine whether epithelialization was present. They performed surgical treatment for 13 patients in whom sequestrae and necrotic soft and hard tissue remained after 4 weeks of STFX administration. Seven cases were treated nonsurgically.

All species in all patients were susceptible to STFX. Scientists say results indicate that STFX, with or without minor surgery, gives a high probability of controlling infection in BRONJ patients with persistent infection despite treatment with common antibiotics, leading to remission and/or complete healing in 95% of patients.



HPV-related cancer outside the oropharynx

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Though research has linked squamous cell carcinoma of the oropharynx with human papillomavirus (HPV), studies on the role of HPV in head and neck squamous cell carcinoma (HNSCC) outside the oropharynx have shown wide contrasts in results.

Researchers in the United Kingdom analyzed cases of patients with HNSCC from 1997-2010 treated at one center to determine incidence of HPV-driven disease outside the oropharynx. Their study was published online in the December 2014 issue of the journal Laryngoscope.

Scientists analyzed 221 samples that were strictly classified to the subsites of oral cavity, larynx or hypopharynx at the time of primary surgery. Formalin-fixed paraffin-embedded samples were subjected to a validated, tiered, diagnostic algorithm of p16 immunohistochemistry, high-risk HPV in situ hybridization and quantitative polymerase chain reaction for HPV E6 DNA. An additional 60 oropharyngeal cases acted as an internal biological control.

Scientists found a 4% incidence of HPV-driven cases across the subsites outside the oropharynx compared to 70% of tumors confined within it. The authors noted that this is the first reporting of a broad range of nonoropharyngeal HPV rates using this validated diagnostic algorithm and it remains unclear whether patients with HPV-driven disease originating outside the oropharynx enjoy the same survival advantage apparent in those patients with HPV-driven oropharyngeal squamous cell carcinomas.

“The small number of HPV-positive cases in nonoropharynx sites does raise questions about the significance of this disease category,” they wrote. “The number of patients in this category remains small, and as mentioned, analysis of pathology, recurrence and prognostic data render meaningful outcome analysis inappropriate. A large multicenter study would be necessary in order to establish if HPV-positive cases from these sites carry a comparable prognostic advantage to those from the oropharynx.”



Steroid inhaler use a risk factor for oral hairy leukoplakia

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Oral hairy leukoplakia (OHL) is a disease of the oral mucosa associated with Eptstein-Barr virus (EBV) infection. EBV is the causative agent of infectious mononucleosis and belongs to the human herpes virus family and occurs in more than 90% of the world’s population. Though OHL was recognized as an opportunistic disease entity in the 1980s associated with the human immunodeficiency virus (HIV) infection, researchers have seen it in patients with a spectrum of immunosuppressive disorders.

Greenspan et al first described OHL in 1984 when they reported a new form of oral leukoplakia found exclusively in homosexual men in the San Francisco area. Since then, the association between OHL and HIV infection or acquired immunodeficiency syndrome has been extensively documented. OHL occurs in up to 50% of patients with untreated HIV infection, mainly affecting those patients with low CD4 counts. OHL has also been reported in individuals with a spectrum of immunosuppressive disorders.

However, OHL has also been identified as a risk factor in patients who have used long-term inhaled, topical and systemic steroids.

For this study, published in the journal Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, scientists in the United Kingdom describe 35 cases of OHL.

They identified patients with non-HIV-association OHL from three centers in the United Kingdom between January 2007 and December 2013. Two oral pathologists reviewed slides and confirmed the diagnosis. Scientists determined patient demographic characteristics, lesion characteristics and medical histories by reviewing biopsy request forms and medical records.
Researchers analyzed the cases of 25 males and 10 females whose average age at the time of diagnosis was 61 years (range 33-86 years). The majority of patients (34 of 35) had lesions located on the tongue, with the lateral border being the site of predilection (25 of 34). Two patients had bilateral lesions affecting the lateral borders of the tongue. The remaining patient had a lesion affecting the floor of the mouth. Twenty-four lesions showed evidence of Candida co-infection.

Twenty-eight patients had intercurrent respiratory problems (asthma or chronic pulmonary disease) requiring regular use of inhaled steroids and four were taking combined inhalation and systemic steroid therapy. Four patients had autoimmune diseases that required treatment with steroids or other immunosuppressant drugs and four patients had diabetes.

“To date, this is the largest case series of non-HIV-associated OHL and confirms the fact that regular use of inhaled high-potency steroids with or without systemic steroids is a risk factor in the development of OHL,” authors concluded. “In the 21st century, the presence of OHL should not be regarded as pathognomic for HIV infection or significant systemic immunosuppression. Local and systemic immunosuppression caused by steroid inhaler use is a risk factor for the development of OHL.”


Pathology CE course, annual meeting planned next month in San Diego

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Join the San Diego County Dental Society and the American Academy of Oral and Maxillofacial Pathology for the daylong continuing education course, Oral Pathology: Helping You Guard Your Galaxy, April 17 at the Manchester Grand Hyatt in San Diego. Drs. Mark Lingen, John Hellstein, John Kalmar and Brad Neville will review the latest on oral cancer and other conditions for dentists and dental specialists, from prevention to diagnosis to management of common and challenging mouth problems dentists regularly encounter in practice. Register or view the program at:


This course is held in conjunction with the AAOMP 69th annual meeting—this year a joint conference with the American Academy of Oral Medicine.

The April 18-24 meeting, Collaboration in Diagnostic Sciences 2015, offers participants a rare opportunity to learn from a cross section of oral medicine specialists and health care experts on a variety of topics that could impact oral medicine and oral pathology. The schedule features continuing education, networking opportunities, an exhibition, social events and more.

Visit http://www.collaborationindiagnosticsciences.com/ to register, view the program or book a room at the Manchester Grand Hyatt.


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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 and maxillofacial pathology, the first 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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