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JADA Specialty Scan - O & M Pathology
JADA Specialty Scan

Smokeless tobacco use and coronary heart disease mortality

Few epidemiologic studies regarding smokeless tobacco (ST) use and health outcomes have been conducted in the United States. The authors used a longitudinal study design to estimate mortality risks in a large sample of people participating in the National Longitudinal Mortality Study (NLMS). The study was published in the July 15 issue of International Journal of Cancer.

The study sample consisted of a subset of people from the NLMS who completed a single Tobacco Use Supplement to the Current Population Survey (TUS-CPS) from 1985 through 2011. The final sample (n = 349,282) was limited to current ST users, former ST users, and never ST users. Excluded from all analyses were people who had ever smoked 100 or more cigarettes or had ever used cigars or pipes, the authors wrote.

The researchers linked NLMS records to cause-specific mortalities via the National Death Index. They selected 5 outcomes based on associations with ST use in published epidemiologic studies: mortality from cancer of the oral cavity or pharynx; mortality from pancreatic cancer; mortality from esophageal cancer; mortality from cerebrovascular disease (stroke); and mortality from coronary heart disease (CHD). Three additional outcomes were all-cause mortality, mortality attributed to all malignant neoplasms, and mortality attributed to malignant neoplasms of digestive system organs, wrote the authors.

At the end of the study on December 31, 2011, most participants (91.7%) were alive. The median and maximum follow-up times were 8.8 and 26.3 years, respectively. Because the study excluded people who had ever smoked cigarettes, cigars, or pipes, the majority (60.2%) of participants were female. However, men were the predominant users of ST (4.8% versus 0.7%). Other demographic variables associated with ever use of ST were non-Hispanic white, younger than 35 years, and high school graduate or less, the authors wrote.

The results of log-rank tests of survival indicated statistically significant differences between current ST users, former users, and never users for only 2 of the 8 outcomes: all-cause mortality (P < .001) and CHD mortality (P < .0001). Pairwise comparisons of the 3 groups revealed statistically significant differences between current ST users and never users for all-cause mortality (P = .03) and CHD mortality (P = .001). The researchers also observed significant differences between former and current ST users for all-cause mortality (P < .001) and CHD mortality (P < .0001).

After adjusting for covariates in the regression models, the researchers observed that the association between current ST use and all-cause mortality was no longer statistically significant (hazard ratio, 1.01 [95% confidence interval, 0.93 to 1.10]). In contrast, the association between current ST use and CHD mortality remained statistically significant after adjusting for covariates (hazard ratio, 1.24 [95% confidence interval, 1.05 to 1.46]). The authors reported that the “adjusted estimate indicates that current ST users [had] a 24% increased risk of dying from CHD relative to the never tobacco users.”

One important limitation of this study was the absence of known CHD risk factors in the TUS-CPS, the authors pointed out, which “raises the possibility of a noncausal association.” These risk factors should be adjusted for in observational studies.

The authors concluded that the elevated risk of CHD mortality among ST users in the study is generally consistent with the findings of other US longitudinal studies. In addition, the “24% increased risk [of] CHD mortality among current ST users is very similar in magnitude to the CHD risk from exposure to secondhand smoke,” the authors noted.

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


Associate Consulting Editor: Zoya Kurago, DDS, PhD
Associate Professor of Oral Biology, Oral Health and Diagnostic Sciences,
Graduate Studies, Pathology
Department of Oral Health and Diagnostic Sciences
Dental College of Georgia, Augusta University

Oral opportunistic infections: diagnosis and treatment considerations

Oral opportunistic infections (OIs) are initiated by exogenously acquired pathogens or resident host flora. In this review article, the authors examine the pathogens and microbiology of oral OIs, diseases observed with oral OIs, risk factors for disease development and progression, and diagnosis and treatment considerations. The study was published in the April issue of Dental Clinics of North America.

Oral OIs are associated with specific pathogens, including many bacteria, yeast, viruses, and parasites. Examples include Prevotella, Staphylococci, Candida, herpes simplex virus, Epstein-Barr virus, and Trichomonas. These microorganisms have unique genotypic and phenotypic compositions and virulence factors. Some possible modes of transmission for acquired OI pathogens are sexual, zoonotic, saliva, blood, food, and droplets.

OIs can be diagnosed via biological, serologic, histologic, or molecular methods. Because of possible false-negative findings and cross-reactivity, practitioners should correlate results with clinical findings and use a combination of diagnostic tests. For dentists in private practice, “one challenge in clinical diagnostic microbiology of oral OIs is limited knowledge of commercial laboratories able to perform all needed tests,” the authors wrote.

Patients with compromised immunity are most susceptible to developing an OI. Thus, comorbidities such as human immunodeficiency virus (HIV), cancer, diabetes, and neutropenia can “play a significant role in susceptibility to oral OI and the course of disease,” the authors pointed out. For example, patients who have undergone transplantation or hemodialysis experience multiorgan disturbances that affect the occurrence of secondary clinical oral manifestations as well as the prevalence and species composition of oral pathogens, the authors wrote.

Examples of OIs that can manifest in the oral cavity and oropharynx are bacterial OIs such as actinomycosis and osteomyelitis, fungal OIs such as candidiasis and histoplasmosis, viral OIs such as herpes zoster virus–associated aggressive periodontitis and Kaposi sarcoma, and parasitic infections such as Chagas disease and toxoplasmosis. Although many of these infections can affect regions other than the oral cavity, some (for example, osteomyelitis in medication-related osteonecrosis of the jaw) affect the oral cavity almost exclusively, the authors wrote. In the context of HIV, early diagnosis of infection and immunosuppression and access to medical care and antiretroviral treatment are important in preventing HIV-related oral disease.

Oral lesions associated with OIs can have a broad range of presentations, such as ulcers, plaques, cysts, wart-like lesions, erosions, granulomas, nodules, sequestrae, and abscesses. The authors noted that “none of these are pathognomonic for a specific disease, but can aid in identifying causes and guide further testing” such as culture, biopsy, or both. The researchers described a patient with a nonhealing area of necrotizing ulcerative gingivitis unresponsive to local treatment and antibiotics; on biopsy, the area was found to represent histoplasmosis, a deep fungal infection. Without the biopsy, the organisms and diagnosis could easily have been missed, and even with the biopsy, the diagnosis was challenging, the authors pointed out.

Achieving improved patient outcomes in cases of oral OI requires a clinical risk assessment and history with review of systems, along with accurate diagnosis, treatment, and follow-up, the authors wrote. Because many of the oral OI-associated pathogens are transmissible or communicable, “infectious disease paradigms apply and consultation may be appropriate in some cases,” the authors wrote.

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Examining the increasing incidence of oral tongue cancer in the United States

The incidence of oral tongue cancer in the United States has reportedly increased in recent years despite significant reductions in tobacco use. The main objective of this study was to identify the demographic subgroups and birth cohorts that have experienced an increase in oral tongue cancer. The second objective was to compare the findings with those for oropharyngeal cancer to determine whether similar birth cohorts experienced an increase in these cancers. The study was published in the April issue of Oral Oncology.

The researchers obtained cancer incidence information from the National Institutes of Health National Cancer Institute’s Surveillance, Epidemiology, and End Results program database from 1973 through 2012. For all analyses, they divided oral cavity cancer sites into 2 groups: oral tongue cancer (anterior two-thirds of the tongue) and other oral cavity cancer sites. In addition, the researchers evaluated oropharyngeal cancers that were potentially associated with human papillomavirus (HPV) (base of tongue, lingual tonsil, soft palate and uvula, tonsil, oropharynx, and Waldeyer tonsillar ring). They conducted analyses separately according to sex and race (white, black, and other).

From 1973 through 2012, 16,206 cases of oral tongue cancer, 67,789 cases of oropharyngeal cancer, and 56,168 cases of other oral cavity cancers were reported, the authors wrote. Most cases across all sites occurred among men (58.5-74.9%) and whites (84.0-88.2%). However, women accounted for a relatively high proportion of oral tongue cancers (41.5%), the authors noted.

The study findings showed that the incidence of oral tongue cancer increased significantly among white women from 1973 through 2012 (annual increase, 0.6%; P < .001) and among white men from 2008 through 2012 (annual increase, 5.1%; P = .004). The magnitude of the absolute increase was similar between white men and women (2.5 versus 2.6 cases per million, respectively). The investigators did not observe an increase in the incidence of oral tongue cancer among men or women of other racial groups.

The investigators found that the overall increase in the incidence of oral tongue cancer among white men and women varied by age, with increases being most apparent among people younger than 50 years (1973-2012, annual increase, 0.7% [P = .02] in men and 1.7% [P < .001] in women).
Regarding the incidence of oropharyngeal cancer, the researchers also observed statistically significant increases among white men (1973-1998 annual increase, 0.8%; 1998-2009 annual increase, 3.8%) and white women (1995-2012 annual increase, 0.7%). However, the magnitude of the increase from 1973 through 2012 was substantially greater among white men than among white women. Among people younger than 50 years, the incidence increased significantly from 1973 through 2004 among white men and from 1973 through 2012 among white women, the authors wrote. Although significant increases in oropharyngeal cancer were also observed among black men, black women, and men of other races, only white men and white women experienced significant increases in the incidence of both oral tongue and oropharyngeal cancers, the authors explained.

The authors concluded that, in contrast to the role of high-risk HPV in oropharyngeal cancer, the risk factors “contributing to the rise in oral tongue cancer cases among young white men and women in the United States are not currently known.” They noted that molecular studies indicate that HPV does not play a major etiologic role in oral tongue cancer. Therefore, studies are needed to generate and test hypotheses regarding risk factors for oral tongue cancer.

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Oral bisphosphonate–associated risk factors for MRONJ after tooth extraction

Tooth extraction has been implicated as a trigger in the development of medication-related osteonecrosis of the jaw (MRONJ). In this study, researchers examined the risk factors for MRONJ after tooth extraction in patients receiving oral bisphosphonate (BP) treatment. The findings were published online April 27 in Osteoporosis International.

In this nonrandomized, retrospective cohort study, researchers pooled individual patient data from 9 institutions belonging to the Japanese Study Group of Co-operative Dentistry with Medicine. The study comprised 2,458 tooth extractions in 1,175 patients (1,014 women, 161 men). The mean (standard deviation [SD]) age of patients was 70.7 (11.7) years, with a range from 23 to 102 years. The mean (SD) duration of oral BP use was 38.5 (37.7) months. The researchers excluded patients receiving intravenous BP treatment, denosumab, or antiangiogenic agents.

The researchers used univariate and multivariate analyses to evaluate risk factors for MRONJ after tooth extraction. Demographic variables included medical background; type and duration of oral BP use; discontinuation of oral BP treatment (that is, a drug holiday) before tooth extraction and duration of discontinuation; any additional surgical procedures, such as an incision, bone removal, and intentional relaxation incision; removal of bone edges; root amputation or suturing; antibiotic administration before extraction; bone loss around the tooth; duration of follow-up; and primary wound healing with no sign of infection. The researchers also evaluated the reason for tooth extraction, number of extracted teeth, and extraction site.

Postextraction MRONJ was diagnosed in 41 cases (1.7%) in 35 patients. The mean (SD) time until diagnosis was 9.5 (4.2) weeks. Patients who developed MRONJ were significantly older than those who did not. Of the 41 cases diagnosed with MRONJ, 20 were managed with conservative treatment (use of an antiseptic mouthrinse, administration of systemic antibiotics, or debridement of separated necrotic bone), 13 were managed with conservative surgical treatment (removal of necrotic bone only), and 8 were managed with extensive surgical treatment (removal of necrotic and surrounding bone), the authors wrote.

The study findings showed that extraction of a tooth in the mandible (P = .04) or in any molar region (P = .001) was a significant predictor of MRONJ, as was extraction of a single tooth (P = .008). Root amputation and an open wound were also significantly associated with the development of MRONJ (P = .046 and P = .012, respectively). However, the authors observed no significant associations between procedure-related factors (such as an incision and bone removal) or use of a pre-extraction drug holiday and the development of MRONJ. They pointed out that “no patients developed MRONJ after receiving complete wound closure with relaxation (relieving) incisions and/or removal of bone edges.”

The multivariate logistic regression analysis confirmed that root amputation (odds ratio [OR], 6.64; P = .001), single-tooth extraction (OR, 3.70; P = .001), bone loss or severe tooth mobility (OR, 3.60; P = .005), and an open wound (OR, 2.51; P = .026) were each significantly associated with MRONJ.

On the basis of the study findings, the researchers recommended use of a minimally traumatic extraction technique, removal of bone edges, and mucosal wound closure.

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AAOMP begins planning for 2019 annual meeting

Mark your calendar for the AAOMP 2019 Annual Meeting in Miami, FL, June 7 – June 12. Watch for more information coming soon at the American Academy of Oral and Maxillofacial Pathology website,


Mark your calendar for the 2018 Joint AAOMP and IAOP meeting
Join AAOMP and the IAOP for our Joint Meeting June 22-June 28, 2018 at the Westin Bayshore Hotel in Vancouver, BC, Canada. Visit for more details.


JADA+ Specialty Scans and JADA+ Scans

JADA+ Specialty Scans and JADA+ Scans are quarterly newsletters updating dentists on the latest research in selected specialties and disciplines in dentistry. ADA Publishing and the consulting editors from the represented specialties and disciplines aggregate and summarize research from previously published materials, each item attributed to its publication of origin. JADA+ Scan specialties and disciplines include endodontics, oral pathology, orthodontics, pediatric dentistry, periodontics, prosthodontics, radiology, cosmetic/esthetic and osseointegration. 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. View past issues here.

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