Focusing on malignant sublingual gland tumors
Research published in the February 2016 issue of Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology focused on sublingual gland tumors — the least commonly occurring of the major salivary gland tumors, yet the most frequently malignant. Despite malignancy rates of 70 to 90 percent, their low incidence limits evidence regarding treatment modalities, survival rates and prognostic factors.
Finding that most of the literature consists of case reports and single institution studies analyzing salivary gland tumors in general, rather than sublingual gland tumors specifically, researchers at the University of California, Los Angeles School of Dentistry sought to determine the demographic characteristics, prognostic factors and optimal treatment outcomes for patients with primary malignant tumors of the sublingual gland.
To investigate, they used data from 210 patients in the U.S. National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) cancer registry that had a diagnosis of a primary malignant sublingual gland tumor. The researchers’ reasoning was that the database had the capability to help elucidate ambiguity with greater statistical power than previous studies because of the larger sample size. In fact, to the authors’ knowledge, the study is the largest population-based analysis of prognostic factors for survival in patients with a diagnosis of a sublingual gland tumor. They analyzed factors contributing to overall and disease-specific survival rates, including age, sex, stage, surgery, histologic subtype and treatment modality.
Results showed that, of the 210 patients in the SEER database with a diagnosis of primary epithelial sublingual gland tumors from 1973 to 2011, the mean patient age was 59 years. Some 53 percent of the patients were female and 47 percent were male. More than three-quarters (77 percent) were white. Mucoepidermoid carcinomas and adenoid cystic carcinomas made up the largest proportion of cancers at 39 percent and 35 percent, respectively. The majority of patients (94 percent) were treated with surgery, and 51 percent had radiation therapy.
In their discussion, the authors noted that compared with the literature, squamous cell carcinoma presented with a higher than expected frequency in their study. They were surprised that only 29 percent of tumors presented at stage III or IV, whereas 32 percent of tumors presented at stage I or II. The stage at presentation was unknown for 39 percent of cases studied. In the previous literature, sublingual gland tumors had been reported to typically present at an advanced stage because they generally manifested as asymptomatic swellings in the floor of the mouth and were often clinically misdiagnosed as a cyst or benign tumor. “Thus, strict screening and early detection of sublingual gland tumors may lead to improved prognosis for patients diagnosed with a sublingual gland tumor,” researchers advised.
Being female was a significant prognostic factor for overall survival and disease-specific survival at five years, an outcome that correlated with survival data in some previous research that analyzed salivary gland tumors as a group. Lower stage at presentation significantly increased both overall survival and disease-specific survival, and this finding is consistent with previous studies analyzing salivary gland tumors overall and sublingual gland tumors specifically.
Surgical therapy significantly improved both overall and disease-specific survival, which is consistent with previous literature. For adenoid cystic carcinomas, radiation therapy improved survival. “The use of adjuvant therapy has been reported to be a positive prognostic factor in previous studies because it has been found to improve locoregional control, but controversy still remains as to its benefit with regard to overall or disease-free survival,” the authors said.
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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
New research on HPV-associated head and neck cancers
A large research project to assess the prevalence of human papillomavirus (HPV) –related markers in samples of head and neck cancers (HNCs) was pursued by a multinational team of researchers.
Strong evidence demonstrating that high risk-HPV (HR-HPV) subtypes are involved in the development of a subset of oropharyngeal cancers (especially base of tongue and tonsil) has emerged during the past 15 years. However, the fraction of HNCs for which HPV infection is the indisputable triggering carcinogenic event is unknown. “The presence of HPV-DNA in HNCs is not sufficient to prove viral causation as it might just reflect a transient infection unrelated to the carcinogenic process,” researchers noted. A study was conducted to explore markers associated with biological and oncogenic activities of HPVs identified in these cancers. Their findings were published online Jan. 28 in Journal of the National Cancer Institute.
With an ultimate goal of generating “robust estimates of the HPV-attributable fractions (HPV-AFs) in HNCs by anatomic site, sex and geography,” scientists collected archived cancer samples of the oral cavity, pharynx and larynx cancers from pathology departments in 44 centers from 29 countries in Europe, Africa, Asia and America. They assessed levels of six markers associated with HPV carcinogenesis using a single protocol to standardize the entire process from sample selection and processing to pathology review and testing.
From a total of 3,680 head and neck samples, 1,374 were from the oropharynx and hypopharnyx, 1,264 from the oral cavity and 1,042 from the larynx. Researchers observed the highest HPV-AFs in the oropharynx, at 22 percent when based on a single biomarker of HR-HPV infection. It was substantially lower in the oral cavity (3 percent) and even lower in the larynx (1.5 percent). Specifically, the probability of an HPV-driven oral cavity cancer was four to seven times lower than that of oropharyngeal cancer. HPV-AFs were highest in South America, central and eastern Europe and northern Europe. Globally, women showed significantly higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central and South America. Subsites within the oral cavity that were more proximal to the oropharynx exhibited higher HPV-AFs than those that were more distal from the oropharynx.
Results also demonstrated differences in HPV-AF estimates by geographic region, sex and age at diagnosis. Researchers speculated that the large and global heterogeneity in HPV-AFs likely reflects trends in temporal, geographical, and sociodemographic shifts in population exposure to both smoking and oral HPV infection, leading to a rapidly evolving epidemiology of HPV-positive HNCs. “It could be hypothesized that the potential carcinogenic effects of highly prevalent tobacco smoking in the oropharynx between the ‘60s and early 1980s dominated over those induced by low prevalent oral HPV infections,” researchers proposed. “Since the 1980s, at least in certain populations, the high smoking/HPV prevalence ratios progressively diminished, and while population exposure to tobacco smoking decreased, exposure rates to oral HPV simultaneously increased because of increasing use of oral sex practices.”
In conclusion, authors said the study presented robust evidence that the fraction of oropharyngeal cancers that were likely driven by HPV infection, mainly HPV16, was substantial (between 18.5 and 22.4 percent), but highly heterogeneous between anatomic subsite, geography and sex. In contrast, the etiologic fraction of HPV in cancers of the oral cavity and larynx was substantially lower than previously reported (4.5 percent) and also less heterogeneous. “Estimation of the real and evolving contribution of HPV to HNCs is key to forecast the future burden of these cancers as well as to inform on the global potential preventative impact of prophylactic HPV vaccination,” the authors advised.
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Common genetic factors in tooth development and distant tumors
Scientists in China predicted that further research on potential risk markers for the development of cancers may lead to a larger role for dentists in caring for overall health. They published their findings online Jan. 13 in Oral Diseases.
Genes, which are active in developmental programs such as odontogenesis, may also exhibit alterations in unrelated processes such as tumorigenesis. Hypodontia, in which patients are missing a tooth or multiple teeth due to a developmental failure, is often associated with genetic factors. Scientists reviewed the evidence associating tooth agenesis with several types of cancer.
For example, 2004 research reported that a gene mutation was responsible for permanent tooth agenesis and colorectal neoplasia in one four-generation family. The study was followed up by 10 years of additional evidence suggesting that hypodontia may be a prospective predictive marker for cancer. A relationship between cleft palate and/or cleft lip and tumor development was published in 2013.
Although these and other studies suggested a possible association between hypodontia and tumorigenesis, the authors acknowledged a lack of consensus on any connection between the two conditions owing to inherent weaknesses in the strength of the published case reports and cross-sectional studies. Specifically, single case reports may not properly reflect populations as a whole, self-reported medical histories that cross-sectional studies rely on may not be precise, and study samples may be too small. The researchers also described two recent studies that argued against an association between tooth agenesis and ovarian and colorectal cancer risk. However, noting that tooth agenesis is a feature of more than 100 syndromes, they did identify seven rare syndromes in which both tooth agenesis and predisposition to cancer are features.
Motivated by knowledge that the identification of risk markers is critical to early stage cancer diagnosis and seeking greater understanding of a possible connection, they conducted a critical review of the molecular association between genes involving both hypodontia and tumor formation. Authors found tooth agenesis genes with close connections to several types of cancer, including breast, colorectal, lung and ovarian.
While acknowledging that the evidence is weak at this point, the authors suggested that there might be common genetic factors affecting both tooth development and some tumors. “Hypodontia has the potential to become a risk marker for future cancer development,” the authors predicted.
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Using CBCT to examine periapical lesions and maxillary sinus abnormalities
Evidence shows that periapical inflammation is often responsible for distinct maxillary sinus (MS) changes. Diffuse pain in the posterior maxilla may be difficult to diagnose because of the relationship between the roots of the maxillary posterior teeth and the MS floor.
Normal sinus mucosa is not visualized on radiographs, but when affected by infection or allergy, it may become thicker and therefore visible on images. Periapical infections in the maxilla may spread along several paths depending on tooth position. Bacteria, their toxins and products of pulpal necrosis may spread to adjacent anatomic structures, such as the MS, and lead to inflammation.
A retrospective study published in the January 2016 issue of Journal of Endodontics demonstrated that maxillary posterior teeth with periapical radiolucent lesions have a high frequency of sinus abnormalities. Although the size of a periapical lesion (PL) was not associated with the frequency of sinus abnormalities, a close spatial relationship between the lesion and the sinus was.
Researchers analyzed 321 MSs via cone-beam computed tomography (CBCT). A total of 143 CBCT images showed at least one posterior tooth with a PL, and 178 showed posterior teeth without PLs. The sample consisted of 200 patients (125 female patients and 75 male patients with a mean age of 41.2 years consecutively selected from a private radiology clinic’s database) seen from January 2009 to July 2013.
Using CBCT imaging to investigate the association of PLs and MS changes, researchers recorded abnormalities in the MS observed on CBCT scans and measured distances between the upper lesion edge and the MS floor.
Researchers found that the most common sinus abnormality in the presence of a PL was mucosal thickening.
“Anatomic knowledge about the relationship between the root apex and the sinus floor as well as its cortical thickness is an important factor in evaluating the spread of odontogenic infection, which occurs through cancellous bone, reaches the cortex of the floor bone, and crosses it more or less quickly depending on the characteristics of the offending agent, host resistance, and physical peculiarities of this path (distance, bone porosity, thickness, blood in cortical bone, and lymphatic vessels),” the authors said.
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Resources on enrolling in, opting out of Medicare available
If you send biopsies to an oral pathology laboratory for a Medicare-eligible patient, you must register with the Centers for Medicare & Medicaid Services (CMS) using Form 855I or Form 855O or formally opt out of Medicare for the oral pathologist to get paid for his or her services.
The easiest of these options is to register with CMS as an ordering and referring provider using Form 855O. It is a much shorter and easier form to complete, and doing so will also allow your patients enrolled in Medicare to get any drugs you have prescribed that are covered under Medicare Part D paid for by Medicare. Medicare will not pay for these drugs if you fail to register by June 1, 2016. This will also allow you to submit claims to Medicare Advantage plans, some of which do cover dental services. If you formally opt out of Medicare, Medicare will not cover oral pathology services, but there are still forms that will need to be filled out and you will not be able to submit claims to Medicare Advantage plans.
Please remember, opting out of Medicare is not the same as doing nothing. A decision tree, frequently asked questions and a tutorial video can be found at https://success.ada.org/en/practice/medicare.
Diagnose pathologies confidently, handle medical conditions safely
The ADA Clinical Kit includes two valuable books to aid in clinical diagnosis and treatment: The ADA Practical Guide to Patients with Medical Conditions plus the The ADA Practical Guide to Soft Tissue Oral Disease, at a savings of $20 off individual prices.
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Patients with Medical Conditions is an evidence-based guide that takes a patient-focused approach to help practitioners deliver safe, coordinated oral health care for patients with medical conditions. This new edition updates all protocols and guidelines for treatment and medications and adds more information to aid with patient medical assessments. Written by more than 25 expert academics and clinicians, the book clearly organizes individual conditions by background, medical management and dental management.
To order the ADA Clinical Kit with both books, call 1-800-947-4746 or go to adacatalog.org. Readers who use promo code 16408E before March 11 can save 15 percent on all ADA Catalog products.
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 first in the series on this topic for 2016. Other Specialty Scan issues are devoted to endodontics, oral and maxillofacial radiology, orthodontics, 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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