2021, Number 3
Periodontal disease associated with non-surgical oncologic treatment: a review of the literature
Full text
Language: English/Spanish [Versión en español]
References: 27
Page: 272-279
PDF size: 158.39 Kb.
ABSTRACT
Introduction: Periodontitis is a multifactorial chronic inflammatory disease characterized by the loss of tooth support. It can be aggravated depending on the patients' systemic condition; procedures can alter periodontal support structures in situations such as cancer treatment. This paper aims to review in the literature the relationship of periodontal disease with cancer treatment in the literature. Material and methods: For the present review, a search was carried out in the databases (SciELO and MEDLINE) using the keywords for SciELO: antineoplastic agents, radiotherapy, periodontal disease, neoplasms, periodontitis and for the MEDLINE database: "antineoplastic agents", "radiotherapy", "periodontal disease", "neoplasms" and "periodontitis". According to the inclusion criteria, the research consulted for this article consisted of systematic reviews, meta-analysis, experimental, observational, and descriptive studies, prioritizing articles from the last seven years, without language restrictions or animal studies. Conclusions: Cancer treatment generates a proinflammatory cellular status that aggravates periodontal disease, increasing the risk of destruction of periodontal tissues. Adequate clinical management is recommended to control the adverse effects on the periodontium.INTRODUCTION
The relationship between periodontitis and cancer is not new. Many studies have revealed the increase of gum disease and the supporting tissue of the oral cavity, and in a significant amount, the risk of appearance of different tumors. It is said that this association could be due to the high and continuous presence of inflammatory mediators derived from bacterial aggression in periodontitis. Likewise, the relationship between cancer and periodontal disease could be because this disease and its treatment bring different symptoms and signs that affect the oral cavity, adapting the environment to become the ideal host for various periodontal pathogens.1
Intensive treatment of a disease such as cancer produces unavoidable effects that can be very toxic; some may be irreversible in normal cells, especially in rapid turnover such as those of the oral epithelium. There is considerable evidence showing the symptomatic effects during and after the cancer treatments, which develop in the patient a significant discomfort and oral disability causing several oral conditions, including periodontal disease. Furthermore, the oral cavity is considered sensitive to chemotherapy and radiation's direct and indirect toxic effects. This is because the risks are increased by other factors such as complex and diverse microbiota, trauma to oral tissues during standard oral function, fungal infections (such as candidiasis), and other bacterial infections. Added to all this is cancer patients' frequently inadequate oral hygiene because their immunosuppressive and psychological condition does not allow their oral health to be a priority.2
In these systemically compromised patients, the physician and dentist's role is essential to determine the best treatment plan and its possible complications. The primary purpose is the constant improvement of the quality of life since an attack of physical irritation, chemical agents, and microbial organisms can trigger painful or infectious conditions in an oral cavity with low biological recovery potential, damaging general and oral levels could become severe and irreversible.3
PERIODONTAL DISEASE
"Periodontitis is a chronic multifactorial inflammatory disease associated with dysbiotic plaque biofilms and is characterized by progressive destruction of tooth support. Its primary features include loss of periodontal tissue support, manifested through clinical attachment loss (CAL) and radiographically assessed alveolar bone loss, presence of periodontal pocketing and gingival bleeding".4,5 This disease is a one of the most important causes of tooth loss in adults.6 It is calculated to have a 45 to 50% prevalence in general, with the most severe form affecting 10 to 12% of the world's population, being the sixth most common disease.7 In periodontitis, pathogenic microorganisms interact with host tissues and cells, causing the release of a broad array of inflammatory cytokines, chemokines, proteolytic enzymes, reactive oxygen species, and other mediators that lead to local irreversible degeneration of the periodontal structures. The systemic dissemination of infectious agents and inflammatory mediators from the oral environment may cause an elevated and sustained systemic inflammatory condition, promoting the pathogenesis of inflammatory processes and cancer.6
CANCER AND RISK FACTORS
Cancer is a disease characterized by alterations in the pathological tissue growth of abnormal cells and is a set of vague clinical manifestations depending on where they are located.8 Bad habits such as smoking (the most crucial risk factor for cancer and the cause of at least 22% of cancer deaths worldwide), alcohol consumption, poor diet, and physical inactivity are the main risk factors for cancer in the world, as well as for other non-communicable diseases.9
Cancer treatment. The fundamental objective of oncologic treatment is to restrict the reproductive potential of tumor cells to induce cell death through apoptosis, necrosis, mitotic catastrophe, and autophagy.10,11 The problem is that cancer treatment mainly targets the tumor cells. Nevertheless, they also act upon rapid-dividing body cells (hair follicles, bone marrow, digestive system, reproductive system, skin, and normal cells close to the tumor).10,11
A correct diagnosis is the first step to establishing a good and effective oncological treatment plan. Each type of cancer requires a specific protocol that may include one or more modalities, such as surgery, radiotherapy or chemotherapy, palliative care, and psychosocial support. The protocol will help cure cancer or prolong the patient's life as much as possible.9,10,12 Together with the prognosis, this protocol will depend on the histological type and the clinical stage, which must be taken into consideration when establishing the therapeutic dosage and number of programmed cycles administered by the specialist.10
It is estimated that of the 60% of patients with cancer who are systemically treated, 40% present oral toxicity, even if the region is not involved in the initial lesion.10,12 Although no technology can entirely protect normal tissues from the side effects of cancer treatment, patients will always experience some degree of therapy-associated toxicity.11
Types of cancer treatment. In most cases, the first step consists of a surgical stage, which involves the resection of the entire tumor and surrounding tissue. In addition, it may include removing lymph nodes, followed by a complete histological examination by step, which has implications for prognosis and the usage of chemotherapy or radiotherapy, alone or in combination.12 It is used in radio-resistant tumors.12,13
Chemotherapy consists of the administration of cytotoxic drugs to interpose, destroy and inhibit the potential growth and reproduction of tumor cells in cancer patients; the administration timing depends on the type, extension of cancer, expected drug toxicities, and the necessary time to recover from these toxicities.12,13 This treatment is classified according to the purposes such as total tumor control, decreasing metastasis, minimizing tumor size, improve the patient's quality of life.14 Chemotherapeutic drugs must be administered, even though they may damage cells in all phases, with undesirable consequences.13,15
On the other hand, radiotherapy applies ionizing radiation to tumors. It is used exclusively at the site of origin, and its objective varies depending on when it is administered.12 It is used for small tumors, individually or in combination with chemotherapy, in cases where the patient presents larger cancerous tumors or to alleviate cancer symptoms, such as pain, hemorrhages, swallowing difficulty, and problems caused by bone metastasis. The damage will depend on factors related to the treatment, such as the type of radiation used, the total dose, or the radiated area.13 The mechanism of action uses ionized atoms, which have the radioactive capacity to cause sublethal cellular damage by generating lesions at the genetic (DNA) and chromosomal levels, causing unspecific and non-selective cell death due to the accumulated radiation.14
Radiation presents different effects according to the time they occur: acute effects: they occur during treatment, are generally reversible, result from the aggravation of pre-existing symptoms or secondary to edema; early delayed: they appear within a few weeks or up to 2-3 months after initiation of radiotherapy; late delayed: they appear three months to 12 years after radiotherapy –generally within the first three years–, usually due to brain areas' necrosis and irreversible).14
NON-
Oral complications related to antineoplastic therapies may be manifestations before the disease or secondary to non-surgical cancer treatments.16 Among the immediate and most frequent complications are mucositis, dysgeusia, and xerostomia; during therapy, bacterial infections such as caries and periodontal disease may appear, aggravated if they were already preexisting.17,18 Gingivitis and periodontitis due to non-surgical cancer treatment appear as secondary lesions due to aggravation of periodontal inflammatory processes before or after therapy. They appear unexpectedly and acutely in the first cycle of treatment and progress with abundant symptoms when they are super-infected by the presence of pre-existing pathogenic microflora in the mouth. Consequences are manifested with tooth mobility until the progressive loss of the teeth.2,19
After treatment, proinflammatory molecules and molecules that activate proteolytic enzymes (such as metalloproteinases) are expressed in the oral mucosa, producing epithelial lesions (ulcers), allowing access and colonization of microorganisms that infect the area and intensify the inflammatory process. In addition, the therapy affects the salivary glands by decreasing saliva production. A few days after starting the treatment, there is a change in the saliva composition, increasing the concentration of sodium and changing from neutral pH 7 to slightly acidic pH 5, thus turning the oral cavity into a suitable environment to promote colonization. These changes accompanied by an alteration in dietary habits, the direct effects of ionizing radiation on the microbiota, and poor oral hygiene contribute to the imbalance of the oral micro-ecosystem giving rise to dental caries, periodontal disease, oral mucositis, and xerostomia, especially after three months of treatment.13,14,18,20,21
Damage to the periodontium. The periodontium is susceptible to high doses of cancer treatment either by chemotherapy or radiotherapy (blood vessels, periosteum, and periodontal ligament are also affected). Changes in cellularity, vascularity, thinning, and disorientation of Sharpey fibers are observed and reduce remodeling and healing potential. Radiographically, a widening of the space corresponding to the periodontal ligament and destruction of the trabeculated bone is observed, which increases the risk of periodontal disease with damage to bone repair.13,14
Generally, in patients not systemically compromised, periodontal destruction is progressive and usually occurs due to the absence or inadequate oral hygiene. In cancer patients, the opposite situation occurs since periodontal destruction arises from an inevitable reduction in salivary volume and changes in its composition, increasing the risk of alveolar bone loss and being more significant at the level of the teeth whose bone was irradiated. In these cases, periodontal disease accelerates. In patients with established chronic periodontitis, it is exacerbated by pain, oral and even systemic infections, causing an increase in morbidity and mortality due to septicemia, mainly in neutropenic patients.13,14,21
Periodontal management before, during, and after cancer therapy. Oral complications with cancer treatment make good oral health an ongoing challenge for dentists.22 Dysbiosis of the physiological habitat of the oral cavity hurts the immune system and even more so in cancer patients in whom it is usually severely compromised.22,23
The goals of oral and dental care are different, and control should be carried out before, during, and after cancer treatment:
- • Before: previous to starting cancer treatment, it is necessary to identify existing oral diseases to treat them and avoid future complications or reduce their severity.24 Removing etiological agents or using 0.12% chlorhexidine rinses is recommended.14,21 Periodontal surgery is not recommended as periodontium is the most common oral and systemic infections site. Teeth with an unfavorable pulp or periodontal prognosis (less than a year in the mouth) or retained teeth included in the radiation area should be extracted 10 days before antineoplastic treatment.14,21 Whether there is a dental implant in the radiation field depends on the professional criteria to remove it, since it is known that metals cause radiation overdose in its area and reduce it in underlying regions.24 Regarding oral hygiene, instruction should be given on toothbrushes, brushing techniques, and toothpaste, avoiding irritating the oral soft tissues.24-26
- • During: it is carried out simultaneously with cancer treatment. The goals are to prevent oral complications and manage the problems.3 This stage is essential and is oriented to executing a strict self-care regime. If necessary, oral hygiene practices should be replaced by the use of gauze, sponges, or cotton swabs impregnated with chlorhexidine (the latter in cases where tissue damage is severe and ulcers, bleeding, and severe pain are present).24,25 If the treatment before cancer therapy has been carried out successfully, at this stage, the dentist will limit himself to performing periodic hygiene controls, radiological controls, and remotivation.3,24,25
- • After: at the end of cancer treatment, the patient's goals will be to maintain healthy teeth and gums and to monitor the long-term side effects of the treatment he has undergone.27 At this stage, the effectiveness of the established oral hygiene measures must be periodically maintained. In addition, oral health status should be monitored; a periodical control is necessary to plan a timely treatment in case of any complication.27 It is not advisable to perform any aggressive intervention such as tooth extractions until six months after the end of chemotherapy or one year after radiotherapy to avoid the risk of osteoradionecrosis.24 The interval between each reevaluation for periodontal control and maintenance of the cancer patient should be every three months to carry out hygiene control and evaluate the use of salivary substitutes that keep the mucosa and gums moisturized.
CONCLUSION
Cancer treatment generates a proinflammatory cellular condition that aggravates periodontal disease, increasing the risk of periodontal tissues destruction. Therefore, adequate clinical management is recommended to control adverse effects on the periodontium.
REFERENCES
Forouzanfar MH, Afshin A, Alexander LT, Biryukov S, Brauer M, Cercy K et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016; 388 (10053): 1659-1724.
Garcia Heredia GL, Osorio Nuñez M, Chong Rivas I, Marinello Guerrero JJ, Garcia del Barco Herrera D. Manifestaciones bucales por radioterapia en pacientes geriátricos con cáncer de cabeza y cuello. Rev Cubana Estomatol. 2017; 54 (4): 1-12. Disponible: http://www.revestomatologia.sld.cu/index.php/est/article/view/1336
Bueno AC, Nogueira MA, Silami de Magalhaes C, Noronha V, Coutens MB, da Silva Freire AR. Enfermedad periodontal en oncológicos: factor indicativo de exodoncias? Acta Odontol Venez. 2010; 48 (1): 66-71. Disponible en: http://ve.scielo.org/scielo.php?script=sci_arttext&pid=S0001-63652010000100011&lng=es.
AFFILIATIONS
1 Residente de Periodoncia. Universidad Peruana de Ciencias Aplicadas. Lima, Perú.
2 Docente de Periodoncia. Universidad Peruana de Ciencias Aplicadas. Lima, Perú.
3 Docente de Ortodoncia. Universidad Peruana de Ciencias Aplicadas. Lima, Perú.
CORRESPONDENCE
Danna Isabella Ysla Huallpa. E-mail: daisays15@gmail.comReceived: Noviembre 2020. Accepted: Octubre 2021.