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JADA Specialty Scan - O & M Pathology
JADA Specialty Scan

Hypodontia and environmental risk factors

Dentist checking patient mouth close-up

Tooth agenesis is a common dental developmental defect. Hypodontia, defined as missing 1 to 6 permanent teeth, is the most common form of tooth agenesis. In a clinical study published online May 23 in Journal of Dental Research, researchers explored the association between nonsyndromic hypodontia and environmental risk factors, including smoking and consumption of alcohol and caffeine during pregnancy. This study evaluated new patients and those receiving treatment at an orthodontic clinic at the University of Otago in Dunedin, New Zealand. Inclusion criteria were 9 years or older, availability of a good-quality baseline panoramic radiograph, and willingness to participate and provide informed consent. Exclusion criteria were teeth missing owing to trauma or extraction and craniofacial syndromes.

One investigator examined patients’ pretreatment panoramic radiographs for missing permanent teeth (excluding third molars). A tooth was recorded as congenitally missing if neither the tooth nor its developmental crypt was present. The investigator also reviewed treatment records to verify that the missing teeth had not been extracted. The final study group consisted of 89 patients, of whom 47 (53%) had agenesis of 1 or more premolars, 29 (33%) had permanent lateral incisor agenesis, 12 (13%) had a combination of premolar and lateral incisor agenesis, and 1 (1%) had premolar, permanent lateral incisor, and mandibular second molar agenesis. The researchers also recruited 253 control participants matched by age and sex to the study group. They had all of their permanent teeth, as assessed by review of panoramic radiographs.

The researchers obtained sociodemographic information from participants and their mothers by means of a questionnaire. Using self-reports, they gathered data about maternal smoking habits (including exposure to second-hand smoke and number of cigarettes smoked per day) during pregnancy, as well as consumption of alcohol (in glasses per week) and caffeine (yes or no). Mothers who smoked for at least 1 month during pregnancy were considered to have been exposed to active smoking. The study findings showed a statistically significant association between hypodontia in patients and maternal smoking habits during pregnancy. Specifically, 10.1% of mothers in the study group smoked between 1 and 9 cigarettes per day compared with 5.1% of mothers in the control group, the authors wrote. Moreover, heavy smoking (> 10 cigarettes per day) was reported by 10.1% of mothers in the study group but only by 3.6% of mothers in the control group.

The authors pointed out several study strengths. First, they adjusted for several confounding factors associated with cigarette smoking, such as alcohol consumption. Second, the strength of the association between heavy smoking during pregnancy and hypodontia (P = .007) suggests a possible biological gradient, which is a known criterion of disease causation by an exposure. Third, the investigators examined risk factors other than smoking, such as caffeine consumption.

Regarding study limitations, the authors noted that the self-reported exposure data might have been affected by recall bias. In addition, having a control group made up of healthy patients with no missing teeth introduced the risk of differential recall bias, because mothers of patients with hypodontia may have a more vivid recollection of exposures than mothers of patients in the control group. Alternatively, social desirability bias might have been introduced if mothers of case patients underreported exposures to smoking or alcohol during pregnancy. The authors speculated that direct damage of neural crest cells from oxidative stress agents such as smoking might help explain a causal relationship between hypodontia and smoking. However, prospective observational studies with larger sample sizes are needed.

Read the original article here.


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


Establishing a prognostic gene signature in patients with squamous cell carcinoma of the tongue

Image of dentist examining a patient's tongue

Squamous cell carcinoma of the tongue (TSCC) is the most common malignancy of the oral cavity. Locally advanced cases are generally associated with a poor prognosis. Microarray studies, a laboratory tool used to detect the expression of thousands of genes at the same time, have identified useful biomarker candidates for cancer of the larynx and other head and neck cancers. However, few biological markers of TSCC that predict patient prognosis have been identified, and their validity is largely unknown. The objective of this study, published online June 27 in Oncotarget, was to establish a prognostic gene signature in patients with locally advanced TSCC who underwent surgical treatment.

The investigators conducted this retrospective study using discovery and validation cohorts. The discovery study consisted of 26 patients with locally advanced TSCC (pStage III/IV) who had undergone surgical resection of the primary tumor at the National Cancer Center Hospital East in Kashiwa, Japan, from November 2009 through January 2013. Histopathologic classification and TNM staging of the tumor specimens were performed according to the World Health Organization classification and Union for International Cancer Control, respectively. For the validation study, the researchers selected published microarray gene expression profile data and accompanying prognostic data from 3 oral squamous cell carcinoma patient cohorts.

The researchers extracted RNA from the surgically resected tissue samples and used commercially available and widely accepted arrays (GeneChip Human Genome U133 Plus 2.0 [Affymetrix] with GCS 3000Dx) to analyze gene expression. To confirm the cDNA microarray findings, a pathologist who was masked to patients’ clinical outcomes performed immunohistochemical staining in a separate cohort of 127 patients who were compatible with the discovery cohort in terms of clinicopathologic factors.

Analysis of the 26 primary tumors based on cDNA microarray findings and protein expression analysis identified 2 distinct molecular profiles associated with different prognoses, including recurrence-free survival, regardless of clinicopathologic characteristics. Researchers were then able to identify 30 prognostic genes associated with recurrence, which were validated in a separate cohort. Several genes identified are known to affect biological behavior of squamous cell carcinoma. The authors suggested that, while the results are promising with respect to the potential for identifying patients who may need more aggressive treatment, prospective studies need to be conducted. It will be important to determine if more intensive postoperative treatment of patients with TSCC with molecularly unfavorable tumors, as defined in this study, will significantly improve rates of relapse and death.

The authors concluded that the successful translation of gene expression profiles to protein expression and the identification of a biomarker suitable for use in routine examination may open the door to developing more personalized treatments with an impact on prognosis for patients with TSCC.

Read the original article here.

American Academy of Oral & Maxillofacial Pathology logo

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.


Sequence analysis of genes in patients with fractures but no extraskeletal signs of osteogenesis imperfecta

Image close up of little boy's broken leg in a cast plaing with his brother

Osteogenesis imperfecta (OI) is the most common genetic bone fragility disorder and is associated with fractures and extraskeletal findings such as discoloration of the sclera and dentinogenesis imperfecta. In patients younger than 21 years with repeated long-bone fractures or vertebral compression fractures but without extraskeletal signs of OI, confirming an underlying genetic bone fragility disorder would be important in establishing a diagnosis, identifying at-risk family members, and carrying out genetic counseling. In this study, researchers assessed patients with a history of repeated long-bone fractures or vertebral compression fractures but no extraskeletal signs of OI by sequence analysis of genes known to be associated with OI. The findings were published in the July issue of Osteoporosis International.

The study comprised 94 patients (age range, 3 months to 20 years) with a significant fracture history—defined as 1 or more long-bone fractures of the lower extremities, 2 or more long-bone fractures of the upper extremities, or 1 or more vertebral compression fractures—but with no obvious extraskeletal symptoms. Patients also had no family history of OI. The researchers measured patients’ height and converted height and weight to age- and sex-specific z scores. They performed dual-energy x-ray absorptiometry in the anteroposterior direction at the lumbar spine. In addition, 2 evaluators independently assessed the lateral spine radiographs for vertebral fractures.

The authors performed sequence analysis of OI-related genes.

The sequence analysis detected disease-causing genetic variants in 26 of 94 patients (28%). Mutations were found in 5 genes: COL1A1 (NM_000088.3), COL1A2 (NM_000089.3), LRP5 (NM_002335.2), BMP1 (NM_001199.3,NM_006129.4), and PLS3 (NM_001136025.4). Seven of the COL1A1/COL1A2 mutations affected triple helical glycine residues, 2 were splice-site mutations, and 2 led to premature termination codons. All but 1 of these COL1A1/COL1A2 mutations are listed in the Osteogenesis Imperfecta Variant Database as known causes of OI. The authors pointed out that the p.Arg1036Gln change in LRP5, which was found in 5 patients, was the single most frequently observed disease-causing mutation in this study.

The authors compared clinical characteristics between 3 genotypic groups: patients with mutations in COL1A1/COL1A2, patients with LRP5 mutations, and patients in whom no mutation was found. All 3 groups had low lumbar spine areal BMD z scores. Patients with LRP5 mutations also had significantly elevated weight z scores, whereas patients with COL1A1/COL1A2 mutations had low height z scores. In addition, patients with COL1A1/COL1A2 mutations had more long-bone fractures (P = .03) than patients in whom no mutations were detected.

Because the genetic information can have important implications for patients and their families, the authors recommend molecular diagnosis in patients younger than 21 years with a significant fracture history but without extraskeletal manifestations of OI.

Read the original article here.


Investigating familial aggregation of oropharyngeal squamous cell carcinoma in a Utah population

Graphic image of a family tree

Each year, more than one-half a million cases of squamous cell carcinoma (SSC) of the head and neck are estimated to occur worldwide. Environmental risk factors include smoking and alcohol consumption, as well as human papillomavirus (HPV) infection in oropharyngeal SCC. In this study, published online October 11 in Head & Neck, researchers used the Utah Population Database (UPDB) to define the familial aggregation and risk to relatives of patients with oropharyngeal SCC (OSCC).

The UPDB consists of a population-based computerized genealogy of Utah beginning in the mid-1880s. These genealogical data have been linked to various statewide databases, including the Utah Cancer Registry, the authors wrote.

The researchers defined oropharyngeal cancer cases by primary site according to the International Classification of Diseases for Oncology, Revision 3. Primary sites included the base of the tongue, lingual tonsil, soft palate, uvula, tonsillar fossa, tonsillar pillar, overlapping lesion of the tonsils, tonsils, vallecula, anterior surface of epiglottis, lateral wall of the oropharynx, posterior wall of the oropharynx, branchial cleft, overlapping lesions of the oropharynx, and oropharynx.

The study sample consisted of patients who were diagnosed with OSCC between 1966 and 2012 and for whom genealogy data were available for at least 12 of 14 immediate ancestors. The researchers assigned participants to 1 of 205 cohorts based on sex, 5-year birth-year range, state of birth (Utah or not), and birthplace (urban or rural). They randomly selected matched controls from the same cohort to which the case participant had been assigned. The investigators estimated cohort-specific cancer rates (by site) from the UPDB by dividing the total number of cases by the total number of patients with at least 12 immediate ancestors in the database. Of 288 patients with OSCC, 283 had at least 12 of 14 immediate ancestors recorded in the UPDB. A total of 211 of these 283 patients were male and 72 were female, 120 were diagnosed before age 60 years, 82 were diagnosed from ages 60 through 69 years, and 81 were diagnosed after age 69 years, the authors wrote. Of the 288 cases of OSCC, 60 were classified as localized, 152 as regional, 45 as distant, and 2 as in situ, and 29 cases were missing staging data. At diagnosis, 105 of the 288 cases were classified as well differentiated, 77 were moderately differentiated, 100 were poorly differentiated, and 6 were undifferentiated.

The investigators used the Genealogical Index of Familiarity (GIF) to test for excess relatedness among patients with a diagnosis of OSCC. Results of the GIF test showed significant excess relatedness among the 168 patients with early-onset (that is, diagnosed before age 65 years) OSCC (P = .002). The authors pointed out that most of these cases were observed among siblings. The study findings also showed a significantly elevated relative risk (RR) only among first-degree relatives of patients with OSCC (RR, 5.31; 95% confidence interval, 1.45 to 13.59; P = .0074). In addition, among the 168 patients with early-onset OSCC, the authors identified 42 with high-risk pedigrees (34 with 2 cases of OSCC, 6 with 3 cases, and 2 with 4 cases). Moreover, other cancers, particularly tobacco-related lung cancer, were noted to occur with increased frequencies in patients with oropharyngeal cancer, as well as in their first-, second-, and third-degree relatives.

The study findings suggest that both shared environmental factors—tobacco, alcohol, HPV—and a heritable contribution are likely responsible for the familial aggregation of OSCC and risk of developing additional malignancies. However, the authors cautioned that extrapolations to other populations should not be made without additional evaluation, as the requirements of this study limited the population analyzed to original Utah pioneer pedigrees (exclusively of Northern European ancestry).

The researchers identified several pedigrees that had an excess number of patients with the disease. Future studies of such pedigrees could lead to identification of specific genetic mechanisms underlying the increased risk, the authors wrote. Because of the significant risks of tobacco- and HPV-related malignancies in relatives of patients with OSCC, preventive health and education measures should target family members as well as patients, the authors concluded.

Read the original article here.


2018 AAOMP and IAOP Joint Meeting set for June 2018

American Academy of Oral & Maxillofacial Pathology and International Association of Oral Pathologists logos

Join the American Academy of Oral and Maxillofacial Pathology and the International Association of Oral Pathologists at a Joint Meeting, June 23-June 28, 2018 in Vancouver, BC. The theme will be 21st Century Diagnostics: Molecular Genetics to Immunohistochemistry.

The conference will feature top international presenters speaking on topics including:

  • Soft tissue and bone sarcomas of the head and neck with emphasis on ancillary studies to include IHC and molecular.
  • Tumor microenvironment.
  • Challenging cases in head and neck pathology.
  • Dermatologic tumors for oral and maxillofacial pathologists.
  • Case studies involving head and neck radiology.
  • Molecular alterations in head and neck cancer/salivary gland tumors/thyroid cancer with emphasis on diagnosis and treatment.
  • Odontogenic tumors: molecular pathology to personalized medicine.

For more information, visit

What’s holding you back from using social media for your practice?

Pages from Dental Practice Success digimag

Social media marketing expert Rita Zamora’s new article in the Fall 2017 issue of Dental Practice Success discusses 5 main arguments that many dentists make and how to overcome them.

More than a million millennials are becoming moms each year, according to the National Center for Health Statistics, and the need to be more active on social media will continue to grow, too, she writes. “Now is a great time to step back and consider what might be holding you back from the visibility and word of mouth social media offers.”

Also in this issue of Dental Practice Success: why it’s important to grow your practice in midcareer with retirement in mind, communications strategies that can enhance your staff performance and satisfaction, how to combat stress and much more.

American Academy of Oral & Maxillofacial Pathology logo

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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