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JADA Specialty Scan - O & M Pathology
JADA Specialty Scan

HPV vaccination and oropharyngeal cancers

Human papillomavirus (HPV) vaccination may be effective in reducing the incidence of oropharyngeal carcinoma (OPC), specifically those cancers of the base of tongue and tonsils that are associated with high risk HPV infection, a team of scientists from the U.S. and Europe reported. “Clearly worthwhile in our view,” is their interpretation of the research on usefulness of vaccination for both boys and girls for the purpose of OPC prevention.  

Published in the Oct. 28, 2015, online edition of Oral Oncology, the team conducted a literature review to describe available human papillomavirus vaccines, experiences with cervical and anogenital prevention programs and the possible role of vaccination in the prevention of high risk HPV-related (HR HPV) OPC.

Two available prophylactic HPV vaccines have demonstrated high efficacy in preventing anogenital HPV infection and consequent development of anal and cervical pre-cancers. However, the impact of vaccination on actual HPV-related cancer rates will not be observable for many years as it may take several decades after infection for cancer to develop.

Nevertheless, the researchers found encouraging evidence in the body of literature to date. Randomized controlled trials (RCTs) have confirmed effectiveness of prophylactic HPV vaccination in reducing cervical cancer risk in young women, as measured by reduction in persistent infection and pre-cancerous changes. Existing RCTs have also shown that both commercially available vaccines — Cervarix and Gardasil — provide additional protection against disease caused by HR HPVs outside the cervix, including anal cancer and genital warts in both women and men.

Although efficacy against recurrent respiratory papillomas, oral HPV infection and HR HPV-related cases of OPC has not been fully evaluated, the authors noted that recent research suggests that HPV vaccination seems effective in preventing oral HPV infection in women and that efficacy is also likely among men.

It is reasonable to expect that these vaccines might also be able to prevent oropharyngeal HPV 16/18 infection because most HPV-related OPC are caused by HPV-16, a genotype covered by both vaccinations, they said. “However, as prevention of oropharyngeal HPV infection by HPV vaccination has not been evaluated in randomized trials designed for this question, the value of vaccination as a prophylactic measure for OPC is still unproven,” they said.

Two studies suggesting that vaccination might be effective in OPC prevention were described. In one, prevalence of oral HPV 16/18 infection was shown to be much lower among young women in the vaccine arm (one of 2,910 subjects) compared to the control arm (15 of 2,924) of the study. In another study — cross-sectional — prevalence of oral HPV infection was significantly lower among vaccinated women age 14-59 than in unvaccinated women.

However, the hope that these vaccines will also prevent oropharyngeal HPV infection and thus HPV-related OPC must be tempered with important considerations, according to the researchers. Among them, there is limited data on vaccine efficacy for oropharyngeal HPV infections. Another is that, “although it is generally assumed that HPV-mediated carcinogenesis in cervical and oropharyngeal mucosa is comparable, this may not be the case at all,” authors said. Also, because the oropharyngeal sites where HPV causes cancer are difficult to inspect and typically require examination by an otolaryngologist or head and neck surgeon, the ability to detect minimal or precancerous lesions in asymptomatic patients is limited.

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

Antiangiogenesis therapy and MRONJ

An in-depth report of the literature on the development of osteonecrosis of the jaws in patients who received medications to suppress growth of new blood vessels was published in the November 2015 issue of Oral & Maxillofacial Surgery Clinics of North America.

Although it is well-recognized that antiresorptive medications, such as bisphosphonates and denosumab play a crucial role in medication-related osteonecrosis of the jaws (MRONJ), recent research has shown that angiogenesis suppression may also be predictive of ONJ. Many traditional chemotherapeutic agents have antiangiogenic properties and there is evolving data to suggest increased incidence of MRONJ and worsening of the condition in patients who receive antiresorptive medications in conjunction with medications that target angiogenesis. Simultaneous use of multiple therapies complicates identification of the causative agent or agents responsible for osteonecrosis in these patients.

“Prospective data are needed to help define whether the incidence of osteonecrosis is the same, additive, or synergistic when antiresorptive agents are used in combination with medications with antiangiogenic properties,” the author of the report advised.

The report showed that various medications are suspected to have a role in ONJ pathogenesis in patients taking antiangiogenic medications with and without concomitant use of antiresorptive medications, including:

  • vascular endothelial growth factor inhibitors; e.g. Bevacizumab;
  • tyrosine kinase inhibitors; e.g. Sunitinib, Sorafenib, Panzopanib, and Axitinib;
  • mammalian target of rapamycin inhibitors; e.g. Everolimus, Temsirolimus, and Sirolimus;
  • immunomodulatory agents with an antiangiogenic profile; e.g. Thalidomide, Lenalidomide, and Pomalidomide.

Read the original article.


Managing patients with potentially precancerous oral lesions

The risk that a potentially malignant disorder (PMD) of the mouth will become a squamous cell carcinoma is unpredictable. Despite clinicians’ ability to identify PMDs, estimates of transformation to malignancy for precursor lesions are wide ranging and retrospective.

Currently accepted treatment for clinically suspicious lesions includes performing an incisional biopsy for histological assessment and grading of dysplasia followed by excision of high-risk lesions and long-term follow-up. Although it is generally believed that the more severely dysplastic the lesion the greater the risk, studies show that conditions which are not classically dysplastic, such as lichenoid lesions, may also undergo malignant transformation. In addition, other disorders such as proliferative verrucous leukoplakia have a high risk of malignant transformation, often in the absence of dysplasia.

Do lesions previously considered innocuous have an increased risk for malignancy? What percentage of oral squamous cell carcinomas develop from PMDs?

A team of scientists in the U.K. sought answers to these questions and published their findings in the November 2015 issue of the British Journal of Oral and Maxillofacial Surgery.

To evaluate the association between precursor lesions and the long-term risk of development of squamous cell carcinoma, scientists retrospectively reviewed the records of 58 patients who had developed SCC at the same site as a previously identified and biopsied oral lesion. They analyzed histopathological reports and diagnoses for both the precursor and subsequent cancerous lesions and case notes were reviewed with respect to age, sex, smoking and alcohol habits. Information about the appearance and site of the precursor lesion, interventions performed, time to development of SCC and differentiation and staging of the tumor was analyzed.

During the 12-year period, only 25 (43 percent) of the 58 cases of SCC developed at the site of previously diagnosed dysplastic epithelial lesions (comprising all grades of dysplasia or carcinoma-in-situ). Of those SCCs that developed at sites without previous epithelial dysplasia, the single most common precursor lesion, in 19 patients of the 38 patients (33 percent), was hyperkeratosis with lichenoid inflammation only. In this group, SCC arose most often on the ventrolateral tongue and floor of the mouth, with a mean malignant transformation time of 29.2 months.

“While the histopathological findings on the precursor lesions did not significantly influence the time to malignant transformation or the staging of tumours, one of our most interesting observations was the high number of non-dysplastic lichenoid lesions that progressed to invasive carcinoma,” authors noted in their discussion. Regarding the time to malignant transformation, they said their findings, which demonstrate a much shorter period than reported by others, indicate that long-term follow-up, probably in specialist clinics, is necessary for patients with clinically suspicious lesions, irrespective of the initial histopathological diagnosis.

“Our findings that incisional biopsy and grading of dysplasia are not always reliable diagnostic or predictive tools add considerable weight to anecdotal reports that cancer may arise in the absence of recognizable dysplasia,” authors said among conclusions.” They called for clinical vigilance and active surveillance of all clinically suspicious oral lesions, irrespective of the initial histological results.

Read the original article.


Oral lichen planus and thyroid disease

Genetics, systemic diseases, medications, dental materials and microbes have all been cited in past decades as potential factors in the etiology of oral lichen planus (OLP). A growing body of newer evidence suggests a connection between thyroid disease and this common condition. Further, a thyroid medication — levothyroxine — has also been significantly associated with OLP.

Findings in current literature suggest that thyroid disorders might be involved in the etiology of OLP, although the authors emphasize that these study designs did not establish causality. Using a large data set of clinical information systematically collected over 20 years, scientists from the University of Gothenburg, in Sweden, compared the incidence and type of thyroid disease in patients with OLP with a sample of people in the general population. They also examined the clinical characteristics of OLP patients with and without thyroid disease.

Scientists collected data from 1,611 patients with OLP and 1,615 patients from the general population. Patients with concomitant OLP and thyroid disease who were taking levothyroxine were also compared with an age- and gender-matched group of patients with OLP without any known thyroid disease or history of using levothyroxine. Ultimately, 108 patients with OLP who were taking levothyroxine were compared with 110 age- and gender- matched patients with OLP not taking the medication.  

Results showed that the prevalence of levothyroxine use among patients with OLP was 10.6 percent compared with 2.5 percent in the general population. Eighty-two (82) of the 108 patients with OLP taking levothyroxine reported that thyroid disease and starting levothyroxine therapy preceded the onset of OLP.

Clinical characteristics of OLP lesions were not significantly different between individuals with OLP taking levothyroxine and those not taking medication. However, at reexamination, patients not taking levothyroxine were significantly more likely to present with erythematous-appearing lesions and complain of more severe symptoms. Additionally, the clinical characteristics of OLP lesions differed between the groups at the follow-up examination six to seven years later. The lesions in the levothyroxine-taking patients with OLP were more reticular and less erythematous at the reexamination compared with the primary examination. In patients with OLP who were not taking levothyroxine, the number of plaque-like lesions increased and the number of reticular and ulcerative lesions decreased. The severity of OLP symptoms decreased from the primary examination to the reexamination in the OLP group taking levothyroxine.

Researchers acknowledged that their study did not seek to establish an etiologic association between thyroid disease and OLP. “However, the fact that 76 percent of the OLP/levothyroxine+ patients reported a diagnosis of thyroid disease with the initiation of levothyroxine use preceding the onset of OLP suggests that some biologic mechanism involved in hypothyroidism could also play a role in the development of OLP, at least in a subgroup of patients.”

Also, scientists found that the course of OLP lesions was different between the OLP patients taking levothyroxine and those not taking it. The severity of lesions was lower and symptoms milder in the OLP group taking levothyroxine when comparing oral status between the primary exam and the re-exam. Authors deduced that patients with concomitant OLP and thyroid disease may represent a specific subgroup of OLP patients with a different clinical presentation of lesions over time.

Among conclusions authors said, “Thyroid disease was more prevalent in patients with OLP than in patients in the general population.”

The report was published in the November 2015 issue of Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.

Read the original article.

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 20-25, 2016.

For more information, visit the AAOMP website.


ADA Clinical Kit covers medical conditions, soft tissue disease

The ADA now offers a kit of two valuable books to aid in clinical diagnosis and treatment. The ADA Clinical Kit includes a new edition of the ADA Practical Guide to Patients with Medical Conditions plus the ADA Practical Guide to Soft Tissue Oral Disease, at a savings of $20 off individual prices.

The Soft Tissue Oral Disease book takes readers through screening examinations, description and documentation, differential diagnosis and guidelines for observation and referral. Well suited as a clinical handbook or review guide, it is replete with color photos, case studies and discussion, along with synopses of best current treatments based on up‐to‐date literature.

Patients with Medical Conditions new second edition updates all the protocols and guidelines for treatment and medications and adds more information to aid with patient medical assessments. The book clearly organizes individual conditions under three headings: background, medical management and dental management. Written by more than 25 expert academics and clinicians, the evidence-based guide takes a patient-focused approach to help practitioners deliver safe, coordinated oral health care for patients with medical conditions.

Sample pages and a table of contents from the Medical Conditions book can be viewed here; for the Soft Tissue book, view them here. To order the ADA Clinical Kit, call 1-800-947-4746 or go to adacatalog.org. Readers who use the code 15423E before Dec. 4 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 fourth 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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