Oral manifestation of post cancer therapy

Oral cancer has become serious health issues. It is owing to a variety of factors including poor hygiene, tobacco usage, chewing tobacco, smoking, and others. Along with surgery and chemotherapy, the most common treatments include radiation therapy and chemotherapy. Patients with cancer may experience oral toxic effects as a result of antineoplastic therapy such as radiotherapy and chemotherapy. A variety of factors inﬂuence radiation, including the oral mucosa’s fast cell turnover rate, the richness and complexity of the oral microbiota, and soft tissue stress during normal mouth function. The present literature review is for awareness regarding the main oral manifestation secondary to post cancer therapy. This is an Open Access (OA) journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.


Introduction
Oral cancer is a major health issue that affects people all over the world. It is a major global health concern, with over half a million new cases diagnosed each year, and its prevalence appears to be rising in emerging nations. 1,2 It is three to seven times more common in India than it is in resource-rich countries. In India, after cervical and breast cancer, oral cancer is the third most frequent malignancy among women. 3 Oral problems can occur with any treatment for head and neck cancer, including surgery, radiation therapy, chemotherapy etc. Oral mucosal problems may potentially be a result of more targeted therapy. Epidermal growth factor inhibitors cause erythematous mucosal reactions, tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors which can also cause isolated aphthous-like lesions and emerging immunotherapies which can cause lichenoid reactions are among these medications. Furthermore, the long-term oral consequences of these treatments necessitate regular oral and dental check-ups as well as meticulous long-term oral care. Before beginning head and neck treatment, it is critical to complete a thorough oral assessment, basic oral care protocols, management of pre-existing dental conditions, and prevention and management of arising oral complications. This is best performed by multidisciplinary teams that include oncology and experienced dental clinicians who provide prompt dental treatment and preventive practises that do not interfere with cancer treatment. [4][5][6][7][8] For many head and neck cancers, radiotherapy, alone or in combination with surgery or chemotherapy, has resulted in a significant rise in cure rates. High doses of radiation in broad areas, such as the oral mucosa, skin, maxilla, mandible, and salivary glands, can cause a variety of unwanted reactions that can occur during or after treatment. Ionizing radiation in normal tissues within the radiation field causes this harm. 9,10 2. Oral manifestation of Post Radiotherapy and C hemotherapy

Mucositis
Patients having head and neck radiotherapy are more likely to develop mucositis as an acute adverse effect. By the third week of treatment, practically all of the patients have developed confluent mucositis. Reduced cell renewal in the epithelium produces mucosal atrophy and ulceration, resulting in mucosal damage. This is followed by pain, burning, and discomfort, which is exacerbated when excessively spicy meals are consumed. 11,12 The influx of inflammatory cells, followed by epithelial breakdown and ulceration, characterises mucositis. It appears 4-7 days after starting a high-dosage course and goes away 2-4 weeks after the treatment is finished. Doxorubicin, bleomycin, fluorouracil, or methotrexate are some of the drugs that are routinely used to treat mucositis. 13

Radiation caries
When individuals are exposed to irradiation, even those who haven't had dental decay in a long time can get radiation caries. The main cause of such injuries is a decrease in the volume of saliva produced and changes in its quality. Radiation also has a direct effect on teeth, increasing their susceptibility to decalcification. 14,15 Radiation caries is primarily caused by radiation-induced damage to the salivary glands, which results in decreased saliva production; however, other causes may play a role. 16,17 Patients are also given drinks containing refined carbohydrates, which increase the likelihood of sugar adherence to dental surfaces.

Trismus and fibrosis
Trismus may appear immediately after the start of radiation. Trismus is most common in patients who have tumours of the palate, nasopharynx, or maxillary sinus. If left untreated, trismus makes eating difficult and other oral therapeutic treatments practically impossible. The primary treatment consists of primarily exercising the affected muscles. Patients are given bite openers or tongueexercising equipment such as tongue blades. Improvement is usually transient, appearing and disappearing within a few hours. To avoid the severity of trismus, it is necessary to exercise at regular intervals. Chronic trismus progresses to muscle fibrosis, and at this point, muscle stretching is not recommended as a treatment option. Exercise should be incorporated into the treatment plan as soon as possible. 18

Osteoradionecrosis
Osteoradionecrosis, an inflammatory disorder caused by ionising radiation to the bones, is one of the most serious side effects of radiotherapy. The osteocytes and microvascular system are irreversibly damaged by this radiation, resulting in a steady decline in micro vascularization. The tissue becomes hypoxic, hypo vascular, and hypocellular. All of these characteristics prevent bone repair, which can lead to necrosis with or without infection. Atrophy, osteoradionecrosis, and pathological fractures come from harm to the remodelling system, which causes atrophy, osteoradionecrosis, and pathological fractures. Tooth extraction and dental illness in irradiated areas have long been known to be significant risk factors for osteoradionecrosis. Because of its low vascularization and high bone density, the mandible is far more prone to osteoradionecrosis than the maxilla. This side effect usually appears after a year of treatment. Undefined cortical damage with or without sequestration is one of the radiologic characteristics. 19-21

Infections
Neutrophils make up 55-70 percent of all white blood cells in circulation. They have the ability to recognise and destroy intruders. Chemotherapy diminishes their numbers, resulting in neutropenia, which promotes the spread of infections. Infections of the oral cavity are widespread, and are often caused by bacteria, fungi, and viruses. 22,23

Bacterial
During neutropenia, it's normal to see a previously asymptomatic tooth that's now causing infection symptoms. In chemotherapy patients, periodontal disease is a common observation. Sialadenitis, particularly of the parotid gland, is uncommon but can cause significant discomfort and swelling. The most common cause of parotid sialadenitis is Staphylococcus aureus. Bacteremia is usually caused by Streptococcus viridans. Toxic effects of Streptococcus mitis include rash, hypotension, palmar desquamation, and acute respiratory syndrome. 22

Fungal
Because of the persistence of neutropenia caused by chemotherapy, fungal infections are more likely to occur. Candida albicans is commonly found in these infections. Angular cheilitis, as well as pseudomembranous, erythematous, and hyperplastic candidiasis, can produce dysgeusia and xerostomia, as well as a burning feeling and general oral pain. 24

Viral
Viruses replicate within a host cell, multiply, and spread to other cells, infecting them. T-lymphocytes mediate cellmediated immunity, which is the initial line of defence against viral infection. As a result, immunocompromised patients, such as chemotherapy patients, are defenceless against viral incursions. 25

Lichenoid reactions (LR)
A lichenoid response is a pathologic condition that affects the cutaneous or mucosal areas, or both, and is characterised by whitish reticular papules and erythematous erosions and plaques in a reticular pattern, as well as radiating striae. LR can either vanish instantly after the agent's action is accomplished, or it can remain active at the same time. 26,27

Dental growth and development alteration
Chemotherapy has a systemic effect, unlike radiotherapy, which only affects the cells within the irradiated zone. As a result, even when far removed from the tumour site, growing odontogenic cells are vulnerable to chemotherapy. In children receiving chemotherapy, researchers discovered delays in dental development, hypoplasia, and microdontia. 28

Xerostomia
Salivary gland function is generally harmed by chemotherapy. This disruption is just transient and can be reversed. However, it creates discomfort, interferes with speaking, and makes chewing difficult. There are higher amounts of amylase and peroxidase. Chemotherapy causes a drop in IgA and IgG levels at the same time. As a result, the oral mucosa becomes vulnerable to damage and oral mucositis. 22

Bleeding
Bone marrow cells are harmed by cytotoxic drugs. Thrombocytopenia can result from this negative consequence. Excessive bleeding may be caused by this bone marrow suppression. Petechiae, hematomas, and ecchymoses are the most common symptoms. During chemotherapy, ecchymoses can suggest a low platelet count. A platelet count of less than 50,000/mm3 is a risk factor for tooth extraction and other invasive procedures. Excessive bleeding is more likely with a platelet count below 20,000/mm3, especially during the early stages of gingivitis. Haemorrhage can occur anywhere in the mouth, including the soft palate, the floor of the mouth, the lower lip, and the vestibular mucosa. 21

Neurotoxicity
Neurotoxicity has been linked to drugs like vinblastine and vincristine. The mandible may experience extreme deep discomfort as a result of the neurotoxicity. The pain goes away a week after the chemotherapy is finished. To help physicians identify the pain from pain produced by pulp problems, detailed exams including as X-rays and intraoral probing are required. Dental sensitivity is usually noticed weeks or months following chemotherapy. Topical fluorides or specially formulated desensitising toothpaste may be effective in reducing symptoms. 23

Oral hyperpigmentation
Imatinib treatment can cause cutaneous and mucosal depigmentation or hyperpigmentation, which has been shown to be dose-dependent and reversible once treatment is stopped. Imatinib has an effect on c-kit, a tyrosine kinase receptor that regulates melanogenesis. C-kit has been found in oral cavity and dental pulp mesenchymal cells. 22

Dysgeusia
Patients may have an unpleasant metallic taste during chemotherapy as a result of chemotherapeutic drug diffusion into the oral cavity. Dysgeusia appears a few weeks after starting cytotoxic treatment and is usually reversible in a few weeks. The chemotherapy drugs cyclophosphamide, methotrexate, and 5-fluorouracil, as well as the protocol agents for days after the infusion, cyclophosphamide, epirubicin, and 5-fluorouracil, as well as their derivatives, can be found in saliva. Damage to specific cranial nerves (VII, IX, X), the oral mucosa, or the taste buds are all part of the pathophysiology of dysgeusia. 29

Conclusion
To minimise patient suffering and morbidity, better awareness of the adverse consequences of radiotherapy and chemotherapy is necessary. Introducing appropriate oral home care and more regular visits to the dentists before cancer treatment will enable for continued care during and after cancer therapy. Dentists should understand the biology of cancer and the range of issues associated with the disease and treatments in order to provide safe dental care. Within the multidisciplinary team, the dentist's responsibility is to ensure dental treatment coordination and prioritisation that is relevant to the patient's medical needs and within their clinical expertise.

Conflicts of Interest
The authors declare that there are no conflicts of interest regarding the publication of this paper.

Source of Funding
None.