Chronic oral diseases secondary to COVID-19 infection or vaccination: clinical cases and a narrative review.

OBJECTIVES: Autoimmune activation by COVID-19 infection/vaccination has been postulated to be responsible for initiating or reactivating multiple types of oral mucosal immune disorders. These include oral lichen planus (OLP); oral pemphigoid, either bullous pemphigoid (BP) or mucous membrane pemphigoid (MMP) with oral involvement; pemphigus vulgaris (PV) with oral involvement; or Sjögren's disease. In addition, chronic conditions such as oral burning, xerostomia or changes in taste and/or smell have also been linked to COVID-19 infection/vaccination. DATA SOURCES: Part 1 (mucosal conditions): an English-language literature review of Pubmed, Web of Science, Scopus, and Embase was performed searching cases of OLP, oral BP, MMP, PV and COVID-19 infection/vaccination, with additional cases from the authors' clinical practice presented. Part 2 (non-mucosal conditions): Cases of initiated or flared Sjögren's disease, chronic oral burning, or xerostomia after COVID-19 infection/vaccination from the authors' clinical practice were aggregated. Our literature review discovered 29 cases of OLP following COVID-19 infection/vaccination. For BP, 10 cases were identified after infection/vaccination. The number of PV cases following infection/vaccination were 28. The majority of mucosal cases were reported after vaccination. Most reported initial disease, but a substantial amount included recurrences of existing diseases. Non-mucosal disease: Sjögren's disease, chronic oral burning, or xerostomia after COVID-19 infection/vaccination cases totaled 12 cases identified from the authors' clinical practice, with the majority occurring after infection. CONCLUSIONS: Chronic conditions after infection with COVID-19 or vaccination remain relatively rare and self-limited, yet reinforce the importance of comprehensive history taking involving COVID-19 to differentiate potential etiologic factors for these conditions.

Clinical and Psychosocial Impact of Communication about Oral Potentially Malignant Disorders: A Scoping Review.

Delivering bad news has been widely studied in cancer, thus, this scoping review aims to identify the available evidence concerning the communication of oral potentially malignant disorders (OPMDs) and their clinical and psychosocial impacts. A search was performed using electronic databases (Medline/PubMed, Scopus, Embase, and Web of Science) and one grey literature database (Google Scholar). Studies focused on communicating the diagnosis of OPMDs and the patients' perceptions were included. Study selection and data extraction were performed by two authors in a two-phase process. Five publications were included in the qualitative analysis. Differences regarding the study design, population, OPMDs assessed, and outcomes of professional-patient communication were found in each study. Protocols for OPMD communication have not yet been reported and there is a need to standardize strategies as communication skills may provide better clinical outcomes for patients diagnosed with potentially malignant disorders. Although future studies are needed, a brief list recommending the aspects that must be communicated is proposed.

Clinical outcomes of dental implants in head and neck cancer patients: An overview.

OBJECTIVE: The aim of this study was to evaluate the clinical outcomes of dental implants (DIs) in patients with head and neck cancer (HNC) treated with radiotherapy (RT), isolated chemotherapy, or bone modifying agents (BMAs). STUDY DESIGN: This study was registered in the Prospective Register of Systematic Reviews (CRD42018102772); conducted via the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist; and based on PubMed, Scopus, Embase, Cochrane Library, Web of Science, and gray literature searches. The selection of studies was performed in 2 phases by 2 independent reviewers. The risk of bias (RoB) was assessed by the Measurement Tool to Assess the Methodological Quality of Systematic Reviews 2. RESULTS: Twenty systematic reviews were included in the qualitative analysis. The majority scored as having high RoB (n = 11). Primary DIs placement in the mandible of patients with HNC subjected to RT doses <50 Gy was associated with better survival rates. CONCLUSIONS: The placements of DIs could be considered safe in patients with HNC in sites of alveolar bone that received RT (≤5000 Gy); however, no conclusions could be made in patients with cancer managed by chemotherapy or BMAs. Due to the heterogeneity of studies included, the recommendation for DIs placement in patients with cancer should be carefully considered. Future better controlled randomized clinical trials are required to provide enhanced clinical guidelines for best patient care.

The Intersectionality between Race, Ethnicity, and Residential-Level Socioeconomic Status in Disparities of Head and Neck Cancer Outcomes: A SEER Study.

BACKGROUND: Head and neck cancer (HNC) mortality differs by race, ethnicity, and socioeconomic status (SES). However, it is unclear whether the relationship between race/ethnicity and HNC-specific mortality varies according to the residence-level SES. METHODS: Data from the Surveillance Epidemiology and End Results database included participants with primary HNC between 2006 and 2017 (followed through 2018) to assess the joint association of race/ethnicity and census-tract level SES Yost-index groups (quintiles) with all-cause and HNC-specific mortalities. Relative survival rates at 1, 5, and 10 years were calculated. Multivariable Cox proportional hazard regression models estimated hazard-ratios and 95% confidence intervals for all-cause mortality, and Fine-Gray subdistribution hazard models for HNC-specific mortality. Cumulative incidence curves for HNC-specific deaths were estimated. RESULTS: 76,095 patients were included in the analysis: 63.2% were <65 years, 73.4% male, and 11.3% non-Hispanic (NH) Black. Most patients (58.3%) were diagnosed at regional or distant stages and 20.6% died of HNC. The five-year relative survival rate increased with SES group, with 51.6% in the lowest SES group, and 74.1% in the highest SES group. NH-Black patients had higher risk of all-cause and HNC-specific mortality than NH-White patients, regardless of the SES group. NH-Asian/Pacific Islander and Hispanic patients had higher risk of HNC-specific mortality in some SES groups. CONCLUSIONS: NH-Black patients of all SES strata had significantly worse outcomes. Other factors, such as healthcare quality, may be associated with persistent disparities. IMPACT: The study highlights the persistence of significant racial disparities in HNC survival across socioeconomic categories. There is need to consider additional factors underlying these disparities.

Photobiomodulation therapy in management of cancer therapy-induced side effects: WALT position paper 2022.

Disclaimer: This article is based on recommendations from the 12th WALT Congress, Nice, October 3-6, 2018, and a follow-up review of the existing data and the clinical observations of an international multidisciplinary panel of clinicians and researchers with expertise in the area of supportive care in cancer and/or PBM clinical application and dosimetry. This article is informational in nature. As with all clinical materials, this paper should be used with a clear understanding that continued research and practice could result in new insights and recommendations. The review reflects the collective opinion and, as such, does not necessarily represent the opinion of any individual author. In no event shall the authors be liable for any decision made or action taken in reliance on the proposed protocols. Objective: This position paper reviews the potential prophylactic and therapeutic effects of photobiomodulation (PBM) on side effects of cancer therapy, including chemotherapy (CT), radiation therapy (RT), and hematopoietic stem cell transplantation (HSCT). Background: There is a considerable body of evidence supporting the efficacy of PBM for preventing oral mucositis (OM) in patients undergoing RT for head and neck cancer (HNC), CT, or HSCT. This could enhance patients' quality of life, adherence to the prescribed cancer therapy, and treatment outcomes while reducing the cost of cancer care. Methods: A literature review on PBM effectiveness and dosimetry considerations for managing certain complications of cancer therapy were conducted. A systematic review was conducted when numerous randomized controlled trials were available. Results were presented and discussed at an international consensus meeting at the World Association of photobiomoduLation Therapy (WALT) meeting in 2018 that included world expert oncologists, radiation oncologists, oral oncologists, and oral medicine professionals, physicists, engineers, and oncology researchers. The potential mechanism of action of PBM and evidence of PBM efficacy through reported outcomes for individual indications were assessed. Results: There is a large body of evidence demonstrating the efficacy of PBM for preventing OM in certain cancer patient populations, as recently outlined by the Multinational Association for Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Building on these, the WALT group outlines evidence and prescribed PBM treatment parameters for prophylactic and therapeutic use in supportive care for radiodermatitis, dysphagia, xerostomia, dysgeusia, trismus, mucosal and bone necrosis, lymphedema, hand-foot syndrome, alopecia, oral and dermatologic chronic graft-versus-host disease, voice/speech alterations, peripheral neuropathy, and late fibrosis amongst cancer survivors. Conclusions: There is robust evidence for using PBM to prevent and treat a broad range of complications in cancer care. Specific clinical practice guidelines or evidence-based expert consensus recommendations are provided. These recommendations are aimed at improving the clinical utilization of PBM therapy in supportive cancer care and promoting research in this field. It is anticipated these guidelines will be revised periodically.

Alveolar bone histological necrosis observed prior to extractions in patients, who received bone-targeting agents.

OBJECTIVE: We reported the alveolar bone histology prior to dental extractions in cancer patients, who received bone-targeting agents (BTA). SUBJECTS AND METHODS: Fifty-four patients were included. Patients underwent extractions, and bone biopsies were taken. RESULTS: Extractions were performed due to pain, swelling, purulence, fistula, and numbness, not responding to treatment, in 40 patients (group A); extractions due to asymptomatic, non-restorable teeth, were performed in 14 patients (group B). Complete alveolar jaw bone histological necrosis was observed in 28 of 40 (70%) patients of group A and none of group B (p < .001). The development of clinical osteonecrosis (MRON) was assessed in 44 patients; 10 patients, who were also treated with Low Level Laser Treatments-LLLT, were excluded from this analysis, as the alternative therapies were a confounding factor. Twelve patients, with alveolar bone histological necrosis prior to extraction, developed medication-related osteonecrosis of the jaw (MRONJ) compared with two patients with vital or mixed vital/non-vital bone (p < .0007). BTAs >1 year and concurrent targeted therapy were also significantly associated with MRONJ (p = .016 and p = .050). CONCLUSION: Pain, swelling, purulence, fistula, and numbness were significantly associated with complete bone histological necrosis prior to extractions and increased MRONJ development. Research is justified to explore whether histological necrosis represents an early stage of osteonecrosis.

Medication-Related Osteonecrosis of the Jaws.

Medication-related osteonecrosis of the jaw is an oral complication in cancer patients being treated with either antiresorptive or antiangiogenic drugs. The first reports of MRONJ were published in 2003. Hundreds of manuscripts have been published in the medical and dental literature describing the complication, clinical and radiographic signs and symptoms, possible pathophysiology, and management. Despite this extensive literature, the pathobiological mechanisms by which medication-related osteonecrosis of the jaw develops have not yet been fully delineated. The aim of this manuscript is to present current knowledge about the complication ragarding to the definition, known risk factors, and clinical management recommendations. Based on this current state of the science, we also propose research directions that have potential to enhance the management of future oncology patients who are receiving these agents.

Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline.

PURPOSE: To provide guidance regarding best practices in the prevention and management of medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer. METHODS: Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. Guideline development involved a systematic review of the literature and a formal consensus process. PubMed and EMBASE were searched for studies of the prevention and management of MRONJ related to bone-modifying agents (BMAs) for oncologic indications published between January 2009 and December 2017. Results from an earlier systematic review (2003 to 2008) were also included. RESULTS: The systematic review identified 132 publications, only 10 of which were randomized controlled trials. Recommendations underwent two rounds of consensus voting. RECOMMENDATIONS: Currently, MRONJ is defined by (1) current or previous treatment with a BMA or angiogenic inhibitor, (2) exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region and that has persisted for longer than 8 weeks, and (3) no history of radiation therapy to the jaws or metastatic disease to the jaws. In patients who initiate a BMA, preventive care includes comprehensive dental assessments, discussion of modifiable risk factors, and avoidance of elective dentoalveolar surgery (ie, surgery that involves the teeth or contiguous alveolar bone) during BMA treatment. It remains uncertain whether BMAs should be discontinued before dentoalveolar surgery. Staging of MRONJ should be performed by a clinician with experience in the management of MRONJ. Conservative measures comprise the initial approach to MRONJ treatment. Ongoing collaboration among the dentist, dental specialist, and oncologist is essential to optimal patient care.

A Severe, Refractory Case of Mucous Membrane Pemphigoid After Treatment With Pembrolizumab: Brief Communication.

Pembrolizumab is a humanized antibody that targets the programmed death-1 receptor expressed in T cells with high selectivity. This therapeutic is of great importance in cancer immunotherapy yet managing the potential immune-related adverse events remains a concern. Here, we report a rare case of mucous membrane pemphigoid in the oral mucosa, upper respiratory tract, and conjunctiva of a patient with ovarian adenocarcinoma without cutaneous manifestation, which persisted even after pembrolizumab discontinuation. A brief review of pembrolizumab-related bullous pemphigoid cases is presented and possible mechanisms underlying these lesions are discussed.

Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis.

Patients undergoing radiation therapy for the head and neck are susceptible to a significant and often abrupt deterioration in their oral health. The oral morbidities of radiation therapy include but are not limited to an increased susceptibility to dental caries and periodontal disease. They also include profound and often permanent functional and sensory changes involving the oral soft tissue. These changes range from oral mucositis experienced during and soon after treatment, mucosal opportunistic infections, neurosensory disorders, and tissue fibrosis. Many of the oral soft tissue changes following radiation therapy are difficult challenges to the patients and their caregivers and require life-long strategies to alleviate their deleterious effect on basic life functions and on the quality of life. We discuss the presentation, prognosis, and management strategies of the dental structure and oral soft tissue morbidities resulting from the administration of therapeutic radiation in head and neck patient. A case for a collaborative and integrated multidisciplinary approach to the management of these patients is made, with specific recommendation to include knowledgeable and experienced oral health care professionals in the treatment team.

Low level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 1: mechanisms of action, dosimetric, and safety considerations.

PURPOSE: There is a large body of evidence supporting the efficacy of low level laser therapy (LLLT), more recently termed photobiomodulation (PBM), for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved, may expand the applications for PBM in the management of other complications associated with HNC treatment. This article (part 1) describes PBM mechanisms of action, dosimetry, and safety aspects and, in doing so, provides a basis for a companion paper (part 2) which describes the potential breadth of potential applications of PBM in the management of side-effects of (chemo)radiation therapy in patients being treated for HNC and proposes PBM parameters. METHODS: This study is a narrative non-systematic review. RESULTS: We review PBM mechanisms of action and dosimetric considerations. Virtually, all conditions modulated by PBM (e.g., ulceration, inflammation, lymphedema, pain, fibrosis, neurological and muscular injury) are thought to be involved in the pathogenesis of (chemo)radiation therapy-induced complications in patients treated for HNC. The impact of PBM on tumor behavior and tumor response to treatment has been insufficiently studied. In vitro studies assessing the effect of PBM on tumor cells report conflicting results, perhaps attributable to inconsistencies of PBM power and dose. Nonetheless, the biological bases for the broad clinical activities ascribed to PBM have also been noted to be similar to those activities and pathways associated with negative tumor behaviors and impeded response to treatment. While there are no anecdotal descriptions of poor tumor outcomes in patients treated with PBM, confirming its neutrality with respect to cancer responsiveness is a critical priority. CONCLUSION: Based on its therapeutic effects, PBM may have utility in a broad range of oral, oropharyngeal, facial, and neck complications of HNC treatment. Although evidence suggests that PBM using LLLT is safe in HNC patients, more research is imperative and vigilance remains warranted to detect any potential adverse effects of PBM on cancer treatment outcomes and survival.

Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols.

PURPOSE: There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed. METHODS: Narrative review and presentation of PBM parameters are based on current evidence and expert opinion. RESULTS: PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength, typically between 633 and 685 nm or 780-830 nm; energy density, laser or light-emitting diode (LED) output between 10 and 150 mW; dose, 2-3 J (J/cm(2)), and no more than 6 J/cm(2) on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (<100 Hz); and route of delivery, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations. CONCLUSION: PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes.

Oral Complications of Cancer Therapy: A Summary Guide for the Clinician.

Oral complications of cancer therapy can be so severe that they can lead to the discontinuation of cancer treatment. This can affect prognosis, patient survival, and alter patient quality of life. Early recognition and management of oral complications in cancer patients is a very important part of the overall treatment. Currently, a large number of cancers are treated at the ambulatory level, and when patients develop oral problems they may seek care from their private dentist. The goal of this manuscript is to discuss common oral complications of cancer therapy, and the role the general dentist can play in diagnosis and management.

Development of tools for the oral health and panoramic radiograph evaluation of head and neck cancer patients: a methodological study.

PURPOSE: Describe the methodology used to construct tools for standardized data collection of head and neck cancer patients (HNCP). METHODS: We constructed the Oral Health Evaluation Tool (OHET) and Panoramic Radiograph Evaluation Tool (PRET) for systematic collection of long-term oral clinical/radiographical complications, prevalence, and severity. Tools were pilot-tested in 50 chemoradiation-treated HNCP >6 months post-therapy. RESULTS: Tools allowed for collection of extensive clinical and radiographical data. A medium of 1.9 years had elapsed since chemoradiation completion. Patients had a median of 6 missing teeth, 32.7% had no decay and a medium of 30% had filled surfaces; 42.9% had moderate-to-severe decay. Reduced/thickened saliva was noted in 85.4% and dry mucosa in 93.9%. Gingival bleeding was present in 75.5% HNCP and attachment loss in 86%. Four patients had trismus. CONCLUSIONS: Tools were user friendly and provided comprehensive, reproducible, and inexpensive means to evaluate post-therapy oral health of HNCP. Validation testing is ongoing.

Dental demineralization and caries in patients with head and neck cancer.

Concurrent chemoradiation (CCR) therapy is a standard treatment for patients with locally advanced head and neck cancer (HNC). It is well documented that CCR causes profound acute and late toxicities. Xerostomia (the symptom of dry mouth) and hyposalivation (decreased salivary flow) are among the most common treatment side effects in this cohort of patients during and following treatment. They are the result of radiation-induced damage to the salivary glands. Patients with chronic hyposalivation are at risk for demineralization and dental cavitation (dental caries), often presenting as a severe form of rapidly developing decay that results in loss of dentition. Usual post-radiation oral care which includes the use of fluoride, may decrease, but does not eliminate dental caries associated with radiation-induced hyposalivation. The authors conducted a narrative literature review regarding dental caries in HNC population based on MEDLINE, PubMed, CLNAHL, Cochrane database, EMBASE, and PsycINFO from 1985 to 2014. Primary search terms included head and/or neck cancer, dental caries, dental decay, risk factor, physical symptom, physical sequellea, body image, quality of life, measurement, assessment, cost, prevention, and treatment. The authors also reviewed information from National Institute of Dental and Craniofacial Research (NIDCR), American Dental Association (ADA), and other related healthcare professional association web sites. This literature review focuses on critical issues related to dental caries in patients with HNC: potential mechanisms and contributing factors, clinical assessment, physical sequellea, negative impact on body image and quality of life, potential preventative strategies, and recommendations for practice and research in this area.

Oral and dental late effects in survivors of childhood cancer: a Children's Oncology Group report.

PURPOSE: Multi-modality therapy has resulted in improved survival for childhood malignancies. The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers provide practitioners with exposure- and risk-based recommendations for the surveillance and management of asymptomatic survivors who are at least 2 years from completion of therapy. This review outlines the pathophysiology and risks for oral and dental late effects in pediatric cancer survivors and the rationale for oral and dental screening recommended by the Children's Oncology Group. METHODS: An English literature search for oral and dental complications of childhood cancer treatment was undertaken via MEDLINE and encompassed January 1975 to January 2013. Proposed guideline content based on the literature review was approved by a multi-disciplinary panel of survivorship experts and scored according to a modified version of the National Comprehensive Cancer Network "Categories of Consensus" system. RESULTS: The Children's Oncology Group oral-dental panel selected 85 relevant citations. Childhood cancer therapy may impact tooth development, salivary function, craniofacial development, and temporomandibular joint function placing some childhood cancer survivors at an increased risk for poor oral and dental health. Additionally, head and neck radiation and hematopoietic stem cell transplantation increase the risk of subsequent malignant neoplasms in the oral cavity. Survivors require routine dental care to evaluate for potential side effects and initiate early treatment. CONCLUSIONS: Certain childhood cancer survivors are at an increased risk for poor oral and dental health. Early identification of oral and dental morbidity and early interventions can optimize health and quality of life.

Associations of oral health items of the Vanderbilt Head and Neck Symptom Survey with a dental health assessment.

OBJECTIVES: The Vanderbilt Head and Neck Symptom Survey (VHNSS) version 2.0 oral symptom subscale addresses underreported oral health issues. We report the associations of xerostomia, dental health, dentures and trismus questions with oral examination findings. MATERIALS AND METHODS: Between May 2011 and April 2012, fifty head and neck cancer (HNC) patients treated with chemoradiotherapy completed the 50-item VHNSS survey, an oral health assessment by a dentist, salivary flow, and inter-incisal opening (IIO) measurements. RESULTS: Patient reported "problems with dry mouth" correlated with unstimulated salivary flow (-0.43, p=0.002). "Cracked teeth" (0.55, p=<0.001) or "difficulty chewing due to teeth" (0.43, p=0.004) correlated with urgent/emergent dental issues identified on clinical exam. Scores of >4 on any dental question identified 83% of patients with urgent or emergent needs. The ROC curve separated routine from urgent/emergent dental issues (0.89, p<0.001). IIO correlated with reported jaw movement "limitations" (-0.43, p=0.002). Small numbers of patients with dentures precluded meaningful analysis of this subsample. CONCLUSIONS: Clinically significant oral health issues pertaining to xerostomia, dental health and trismus may be identified using the oral health subscale of the VHNSS version 2.0. MASCC guidelines should be followed by patients with xerostomia. The observation that a score of >4 is highly predictive of dental issues is important and needs further validation. If confirmed, this would be a useful screening tool for identifying and referring HNC patients for dental care. Patients with trismus should receive physical therapy.