Available via license: CC BY
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EDITED AND REVIEWED BY
Ali-Farid Safi,
Craniologicum - Center for Craniomaxillofacial
Surgery, Switzerland
*CORRESPONDENCE
Nathaniel S. Treister
ntreister@bwh.harvard.edu
SPECIALTY SECTION
This article was submitted to Oral Cancers, a
section of the journal Frontiers in Oral Health
RECEIVED 05 December 2022
ACCEPTED 19 December 2022
PUBLISHED 26 January 2023
CITATION
González-Arriagada WA, Ottaviani G, Dean D,
Ottaviani G, Santos-Silva AR and Treister NS
(2023) Editorial: Oral complications in cancer
patients.
Front. Oral. Health 3:1116885.
doi: 10.3389/froh.2022.1116885
COPYRIGHT
© 2023 González-Arriagada, Ottaviani, Dean,
Ottaviani, Santos-Silva and Treister. This is an
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comply with these terms.
Editorial: Oral complications
in cancer patients
Wilfredo Alejandro González-Arriagada1,2 , Giulia Ottaviani3,
David Dean4, Giulia Ottaviani5, Alan Roger Santos-Silva6
and Nathaniel S. Treister7*
1
Facultad de Odontología, Universidad de los Andes, Las Condes, Chile,
2
Centro de Investigación e
Innovación em Biomedicina, Universidad de los Andes, Las Condes, Chile,
3
Anatomic Pathology, Lino
Rossi Research Center, Department of Biomedical, Surgical and Dental Sciences, Università degli
Studi di Milano, Milan, Italy,
4
Department of Oral Medicine, Fred Hutchinson Cancer Center,
University of Washington, Seattle, WA, United States,
5
Department of Medicine, Surgery and Health
Sciences, University of Trieste, Trieste, Italy,
6
Oral Diagnosis Department, Oral Medicine
(Stomatology), Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba, Brazil,
7
Division of Oral Medicine and Dentistry, Brigham and Women’s Hospital and Harvard School of
Dental Medicine, Boston, MA, United States
KEYWORDS
cancer therapy, chemotherapy, oral complications, oral mucositis, oral health,
radiotherapy, xerostomia, immune checkpoint inhibitors
Editorial on the Research Topic
Oral complications in cancer patients
Cancer is the second leading cause of death worldwide and future projections place it as
the leading cause by 2040 (1,2,Salazar-Gamarra et al.). Current strategies of treatment
include surgery, chemotherapy, radiotherapy, cellular therapies—e.g., stem cell
transplantation, chimeric antigen receptor (CAR)-T therapy, bone-modifying agents,
immune checkpoint inhibitors (ICIs), and others. These therapies, especially in
advanced cancers, produce direct and indirect toxicities involving the oral cavity and
neighboring regions. For this reason, it is essential to recognize the role that trained
dentists provide in the multidisciplinary teams that treat cancer patients (Harris et al.).
Roles include comprehensive dental evaluation and treatment to decrease infection risk
prior to initiation of cancer therapy (Yong et al.), intra-therapy assessment to mitigate
acute oral toxicities, and long-term follow-up posttreatment therapy to diagnose and
manage late complications including, in some cases, prosthodontic rehabilitation
(Salazar-Gamarra et al.). The inclusion of dentistry in this multidisciplinary approach
is highly beneficial to the patient, but is not yet universal (3).
Oral complications associated with cancer therapy are frequent and can be classified
as early or late onset. Early, or acute complications, are those that begin during therapy
and resolve within 1 month of completion. Acute complications include oral mucositis,
dysgeusia, hyposalivation, candidiasis, radiodermatitis, and dysphagia. Late, or chronic
complications, develop after completion of therapy and in some cases may be
permanent. Chronic complications include hyposalivation, trismus, radiation caries,
osteonecrosis, and dysphagia, among others. In addition, head and neck cancers often
require surgery to treat the primary tumor and regional metastases (neck dissection),
resulting in permanent physical sequela requiring multidisciplinary therapy to address
TYPE Editorial
PUBLISHED 26 January 2023
|
DOI 10.3389/froh.2022.1116885
Frontiers in Oral Health 01 frontiersin.org
functional and social impacts. This topic was chosen to provide
new insights into the epidemiology, pathobiology, impact, and
management of oral toxicities in cancer patients with the goal
of improving patient quality of life.
Mucositis is the principal dose-dependent oral complication
of cancer therapy and may lead to interruption of the treatment.
Oral mucositis (OM) may trigger febrile neutropenia and
blood stream infection and is also commonly associated with
feeding problems and the introduction of enteral nutrition
(Zecha et al.). Oral mucositis is associated with increased
use of hospital resources, physician and multidisciplinary
consultations, and prolonged hospitalization (including
treatment in intensive care units), increasing cost of care, and
the economic burden to patients, in both private and public
health systems across various cancer treatment modalities (4).
Photobiomodulation, delivered intraorally and extraorally, has
shown promising results in OM, including different
management approaches, both preventive and curative (Adnan
et al). It has also been reported to prevent severe hyposalivation
related to radiation therapy (Gobbo et al).
The etiology of oral mucositis has been linked to the direct
effects of chemotherapy and radiation in addition to the effects
of microbiological co-infection, including the oral-gut axis
microbiome. This suggests that control and treatment of
microorganisms could be a novel and successful approach to
reduce mucositis severity (Al-Qadami et al.). Changes in the
microbiome of the oral cavity are related to alteration in saliva,
and probiotics have been proposed as an alternative to reduce
circulating bacteria and candida in the oral environment
(Pispero et al.).
Chronic graft-versus-host disease (GVHD) can broadly
impact the oral cavity and oral function in patients
undergoing allogeneic hematopoietic cell transplantation.
Manifestations include lichenoid mucosal inflammation,
lymphocyte-mediated salivary gland dysfunction and
associated dental caries, taste and smell disturbances, and
trismus. Patients with chronic GVHD are also at increased
risk for oral cavity second primary tumors, particularly oral
squamous cell carcinoma (Dean and Sroussi and Boor et al.).
Immune checkpoint inhibitors have been associated with
similar immune-mediated oral toxicities which are still being
characterized (Klein et al.).
Salivary gland dysfunction is a potentially permanent side
effect of multiple cancer therapies, including head and neck
radiation therapy, chronic GVHD, and ICIs. Hyposalivation
contributes to the development of caries, candidiasis, and
psychological complications related to difficulties in nutrition
and social interaction (Vistoso Monreal et al.). Additionally,
candidiasis is a common opportunistic infection in cancer
patients, secondary to hyposalivation and changes in the
quality of saliva.
Radiation caries is a frequent complication of head and
neck cancer therapy, characterized rapid onset and
destruction of dentition when not promptly diagnosed and
treated. Radiation caries can lead to pain, infection, and
compromised function. Resulting dental extractions are
associated with increased risk of osteoradionecrosis (ORN),
which may require extensive surgical resection (Vistoso
Monreal et al.). Dental restorations in cancer patients have
been shown to have reduced longevity, however, this has yet
to yield technological advancement in dental adhesives,
resins, and other materials specially designed for patients
treated with head and neck radiotherapy (Pedroso et al.). A
similar pattern of rampant caries can be observed in GVHD
patients. Limited opening secondary to trismus can impede
oral hygiene and dental follow-up. Currently, physiotherapy
is the first option, but the results are vague and uncertain,
giving space to the introduction of surgical alternatives
(Smeets et al.).
Osteonecrosis of the jaw can be one of the most impactful
late complications, particularly in more extensive cases.
Medication-related osteonecrosis of the jaw (MRONJ), like
ORN, can be very challenging to manage and may require
aggressive surgical resection (Singh et al.). MRONJ is
characterized by the exposed necrotic bone and may be
related to drug therapy, including antiresorptive and
antiangiogenic targeted therapies (Migliorati). Conservative
therapy is favored as the first-line intervention and may
include irrigation with chlorhexidine, sequestrectomy, and
pharmacological coverage with systemic antibiotics and
pentoxifylline and tocopherol (Migliorati and Singh et al.).
This condition is clinically like ORN, but the differences in
etiology and risk factors may affect its treatment and
prognosis.
Strategies for risk prediction of oral toxicities related to
cancer therapies are needed for a personalized prevention
protocol (Sonis) and they have been primarily used in OM.
Artificial intelligence and machine learning approaches have
been proposed for risk prediction of toxicity for cancer
therapy in patients with head and neck cancer (Fanizzi et al.).
These strategies have great benefits for the patients and
oncologic services because the use of resources is most
efficient and effective, reducing the high costs of prevention
and treatment of collateral effects.
The rapid evolution of oncologic therapies requires
specialists to constantly update themselves to respond to the
requirements of patients and their services. It is important to
draw attention to the fact that many clinical trials report oral
complications in a superficial and protocol-directed manner.
We believe that these toxicities need to be considered during
the study design stage, including oral medicine expertise
within the research team, in order to best characterize these
conditions.
This Research Topic provides a glimpse into this
complex and ever-evolving oncologic realm of clinical oral
medicine.
González-Arriagada et al. 10.3389/froh.2022.1116885
Frontiers in Oral Health 02 frontiersin.org
Author contributions
WG-A wrote the first draft of the manuscript. GO (2nd
author), DD, GO (4th author) and AS-S guided and revised
the manuscript. NT conceptualized and guided the editorial.
All authors contributed to the article and approved the
submitted version.
Funding
GO (2nd author) was supported, in part, by the “Piano di
Sostegno alla Ricerca (PSR) 2020, Linea 2: Dotazione Annuale
per attività istituzionali”, Department of Biomedical, Surgical
and Dental Sciences, Università degli Studi di Milano, Milan,
Italy. WG-A was supported by Fondecyt Regular number
1190775 from Chilean National Agency for Research and
Development.
Conflict of interest
The authors declare that the research was conducted
in the absence of any commercial or financial
relationships that could be construed as a potential
conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of
the authors and do not necessarily represent those of
their affiliated organizations, or those of the publisher, the
editors and the reviewers. Any product that may be
evaluated in this article, or claim that may be made by its
manufacturer, is not guaranteed or endorsed by the
publisher.
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