Skip to main content

A time-dependent subdistribution hazard model for major dental treatment events in cancer patients: a nationwide cohort study

Abstract

Background

Dental care in cancer patients tends to be less prioritized. However, limited research has focused on major dental treatment events in cancer patients after the diagnosis. This study aimed to examine dental treatment delays in cancer patients compared to the general population using a national claims database in South Korea.

Method

The Korea National Health Insurance Service-National Sample Cohort version 2.0, collected from 2002 to 2015, was analyzed. Treatment events were considered for stomatitis, tooth loss, dental caries/pulp disease, and gingivitis/periodontal disease. For each considered event, time-dependent hazard ratios and associated 95% confidence intervals were calculated by applying a subdistribution hazard model with time-varying covariates. Mortality was treated as a competing event. Subgroup analyses were conducted by type of cancer.

Results

The time-dependent subdistribution hazard ratios (SHRs) of stomatitis treatment were greater than 1 in cancer patients in all time intervals, 2.04 within 30 days after cancer diagnosis, and gradually decreased to 1.15 after 5 years. The SHR for tooth loss was less than 0.70 within 3 months after cancer diagnosis and increased to 1 after 5 years. The trends in SHRs of treatment events for other dental diseases were similar to those observed for tooth loss. Subgroup analyses by cancer type suggested that probability of all dental treatment event occurrence was higher in head and neck cancer patients, particularly in the early phase after cancer diagnosis.

Conclusion

Apart from treatments that are associated with cancer therapy, dental treatments in cancer patients are generally delayed and cancer patients tend to refrain from dental treatments. Consideration should be given to seeking more active and effective means for oral health promotion in cancer patients.

Peer Review reports

Background

Dental care for cancer patients is an important issue because diminished masticatory function in cancer patients or survivors can affect their quality of life by increasing stress and depression [1]. While oral complications resulting from cancer or cancer therapies have been relatively under-recognized compared to other complications, the increasing number of cancer survivors has prompted a wider acknowledgement of the need for more active oral management to ensure long-term well-being [2].

The oral complications related to cancer therapy (e.g., chemotherapy, radiotherapy, targeted agents, and immunotherapy) include stomatitis, dental caries, periodontal disease, and dysphagia, with potentially debilitating effects [2, 3]. Stomatitis, which is a common side effect that results from the loss of integrity of the oral mucosa and inflammatory lesions, occurs in 40% of cancer patients who receive chemotherapy, 76% of those who undergo hematopoietic stem cell transplantation, and nearly 100% of those who receive radiotherapy [4, 5].

Pain, the primary morbidity of stomatitis, may lead to significant problems in food intake, causing weight loss and secondary infection due to nutritional deficiencies [6]. Severe stomatitis degrades patients’ quality of life by frequent emergency department visits or hospitalizations and increases the costs of care due to antibiotic administration or prolonged hospitalization [7]. It can also affect the maintenance of cancer treatment by leading to undesirable breaks in radiotherapy or the discontinuation of planned chemotherapy [8, 9]. Patients undergoing radiotherapy targeting the head and neck are particularly susceptible to a significant deterioration in their oral health. The oral morbidities of radiotherapy include increased susceptibility to dental caries, periodontal disease, and oral mucositis during and after treatment, and these may have harmful effects on daily life function and therefore on quality of life [10]. However, previous oral health-related quality of life studies on head and neck cancer patients undergoing radiotherapy have found that patients’ interest in and prioritization of oral health during treatment tended to decrease compared to pre-treatment due to treatment-related side effects [11, 12].

In this nationwide population-based study using the Korean National Health Insurance Service (KNHIS) claims database, we evaluated the occurrence of incident major dental treatment over time after cancer diagnosis in cancer patients compared to a matched sample of the general population comprising individuals who were never diagnosed with cancer during the entire observation period. We also explored how trends in the occurrence of time-dependent events differed by type of cancer.

Methods

Data source

We used the Korean National Health Insurance Service-National Sample Cohort (KNHIS-NSC) version 2.0. This database, established in 2016, is based on administrative claims data from one million people (2% of the whole population), representing the 48 million people who held national health insurance or were eligible for medical care in South Korea from 2002 to 2015. The cohort comprises data from all clinics and hospitals, including information on diagnoses and comorbidities, demographic characteristics, prescriptions, medical services (i.e., treatments and procedures), and costs for inpatients (i.e., those admitted to the hospital) and outpatients (i.e., those who received ambulatory care). It also contains insurance eligibility data, including information on participants’ identity and socioeconomic variables such as sex, residential area, type of health insurance, level of income, type and grade of disability registered, birth, and death.

Ethics statement and guideline

This study followed the Statement of Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines [13]. The study protocol was approved by the Institutional Review Board (IRB) of Seoul National University College of Medicine/Seoul National University Hospital, Korea (approval no.: E-1911-012-1076). All methods were performed in accordance with the relevant guidelines and regulations approved by the IRB. The requirement for informed consent was exempted by the IRB of Seoul National University College of Medicine/Seoul National University Hospital, Korea since the KNHIS-NSC dataset comprises de-identified secondary data for research purposes in a fully anonymized form. Restricted access to the database for the study purpose was authorized by the National Health Insurance Sharing Service (NHISS) in Korea (Research Management No.: NHIS-2020-2-144).

Definition of study participants

Cancer patients were defined as individuals for whom at least one claim was made with hospitalization under a main disease code corresponding to cancer according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10), or three or more claims were made for a main disease code of cancer within a year since 2006. Those who had cancer diagnoses between 2002 and 2005 were excluded. The control group was defined as individuals with no claims for cancer disease codes throughout the entire period. Those who were younger than 6 years at the time of 2006 or had any missing period due to loss of eligibility for the national insurance system during the follow-up period were excluded.

We randomly assigned an individual from the control group to each cancer patient at a 1:1 ratio after matching by age, sex, residence, and income level in the cancer diagnosis year using an exact matching method. In total, 39,625 cancer patients and a matched control group were selected. For each matching set, the cancer patient and the matching participant were followed from the index date when the cancer patient had his or her first cancer diagnosis until when a dental treatment event of interest occurred, the participant died, or the participant was censored.

Variables under study

Treatment event outcomes were identified from the claims data for four dental diseases: stomatitis, tooth loss, dental caries/pulp disease, and gingivitis/periodontal disease. For the operational definition of outcomes, clinical opinions and definitions validated in previous studies were considered [14,15,16]. An event of treatment for stomatitis was defined as a case in which at least one claim was made with a relevant disease code. Events for tooth loss, dental caries/pulp disease, and gingivitis/periodontal disease were defined as cases in which at least one claim was made with a relevant disease code together with a disease-related treatment code. The relevant treatment codes for each disease were identified on the basis of the Health Insurance Medical Care report published by the Korean Health Insurance Review and Assessment Service (see Additional file 1: Table S1) [17]. The outcome of death was defined as a case in which beneficiaries lost their qualification due to death identified from the insurance eligibility data. Death was considered as a competing event for the outcomes of major dental treatment events.

Statistical analysis

For each event of interest, we estimated the relative risk (RR) as a ratio of the proportions of the outcome in the control and cancer patients, and the hazard ratio (HR) was also calculated using the Cox proportional hazard regression method [18].

The proportional hazard assumption was explored by a log-minus-log plot. When the assumption was considered invalid, intervals for varying HRs were determined based on clinical advice and the exploration of the log-minus-log curves for any significant points of intersection.

A time-dependent HR of each treatment event was generated by applying a subdistribution hazard model with time-varying covariates [19], which is an extended Cox model accounting for time-varying covariates as well as time-independent covariates, considering death as a competing risk for the outcomes of treatment events. The subdistribution hazard ratio (SHR) was estimated at each defined interval and 95% confidence intervals (CIs) were computed.

Baseline diseases were considered as covariates for adjustment, and they primarily included diabetes, hypertension, hyperlipidemia, arthritis, osteoporosis, infectious disease, gastrointestinal disease, cardiovascular disease, and cerebrovascular disease. The baseline diseases were defined operationally as cases in which two or more disease-related codes were found within a year prior to the follow-up period. For diabetes, hypertension, and hyperlipidemia, cases where a disease-related code and at least one record of relevant medication prescribed for the disease were found were also included as indicators of baseline disease. A history of any dental disease of interest (i.e., stomatitis, tooth loss, dental caries/pulp disease, and gingivitis/periodontal disease) within a year prior to beginning of the follow-up period were also considered as a baseline disease covariate for adjustment (see Additional file 1: Table S2).

A subgroup analysis was performed by type of cancer in consideration of the cancer treatment site (oral cancer, other head and neck cancer, thyroid cancer, other solid cancer, and blood cancer) (see Additional file 1: Table S3).

All statistical analyses were performed using R version 3.3.3 [20] and SAS Enterprise Guide software (version 7.1; Copyright © 2003 SAS Institute Inc., Cary, NC, USA).

Results

Cohort characteristics

There was no significant difference between the groups in age, sex, residence, and income level, which were used as matching variables (p = 1.00). No significant differences between groups were found in the history of tooth loss, dental caries/pulp disease, and gingivitis/periodontal disease (p = 0.71, p = 0.55, and p = 1.00, respectively), whereas a significantly higher proportion of cancer patients had experienced stomatitis at baseline (p < 0.01). Gastrointestinal disease was present in 39.2% of cancer patients but in 28.5% of the control group (p < 0.01). The prevalence of all the other baseline diseases showed differences of less than 3% points between cancer patients and the control group, but the differences were still statistically significant at the 0.05 level (Table 1).

Table 1 Cohort characteristics

Major dental treatment events and mortality and time-dependent hazard ratios

The proportion of stomatitis treatment events was significantly higher in cancer patients than in the control group (RR = 1.15; 95% CI 1.11–1.18), whereas the proportions of treatment events for tooth loss, dental caries/pulp disease, and gingivitis/periodontal disease were significantly lower in cancer patients (RR = 0.74; 95% CI 0.70–0.77, RR = 0.85; 95% CI 0.84–0.87 and RR = 0.81; 95% CI 0.80–0.82, respectively). The incidence of death in the cancer patients was 4.5 times higher than that in the control group (RR = 4.58; 95% CI 4.41–4.76). As analyzed in terms of time-to-event, the probability of treatment event occurrence for dental caries/pulp disease and gingivitis/periodontal disease in cancer patients became similar but slightly higher than those in the control group, and the estimated hazard ratios were statistically significant (HR 1.10; 95% CI 1.07–1.13 and HR 1.03; 95% CI 1.01–1.05, respectively). The hazard ratios for stomatitis, tooth loss, and death appeared in consistent directions to what the risk ratios showed (HR 1.52; 95% CI 1.46–1.57, HR = 0.95; 95% CI 0.91-1.00 and HR 5.59; 95% CI 5.36–5.83, respectively) (Table 2).

Table 2 Relative risks (RRs) and hazard ratios (HRs) for cancer patients compared to the control group

In log-minus-log plots, the graphs of cancer patients and the control group intersected for every dental disease of concern, which indicated that the assumption of a constant HR over time did not hold (Fig. 1). Mortality as a competing event for each dental disease was at least twice as high in cancer patients compared to that in the control group in all time intervals, and the highest excess risk was observed in the period from 30 days to 3 months, with a 16-fold difference (Table 3).

Fig. 1
figure 1

Log-minus-log plots for time to major dental treatment events. Each plot represents stomatitis (A), tooth loss (B), dental caries/pulp disease (C), and gingivitis/periodontal disease (D). The solid line shows cancer patients, and the dotted line corresponds to the control group. Follow-up time is expressed as log(years)

Table 3 Time-dependent subdistribution hazard ratios (SHRs) of major dental treatment events considering death as a competing event

The results of the SHR of a treatment event for each dental disease, considering death as a competing event, are presented in Table 3; Fig. 2. The probability of stomatitis treatment event occurrence was greater in cancer patients than in the control group in all time intervals (SHR > 1), with statistical significance at 0.05 level. The SHR was 2.04 (95% CI = 1.60–2.58) within 30 days after cancer diagnosis and gradually decreased to 1.15 (95% CI 1.04–1.28) after 5 years.

Fig. 2
figure 2

Time-dependent subdistribution hazard ratios (SHRs) of major dental treatment events. The time-dependent SHRs are expressed by points according to the follow-up period. The mortality was considered as a competing event. The bold line represents a hazard ratio of 1.0, indicating the same risk between cancer patients and the control group

The probability of treatment event occurrence for tooth loss was lower in cancer patients than in the control group in all time intervals (SHR < 1), and the SHR was less than 0.7 within 3 months after cancer diagnosis (0.65; 95% CI 0.50–0.84 and 0.54; 95% CI 0.43–0.68 before and after 30 days, respectively) and increased to 1 after 5 years. The estimated SHRs until 5 years after cancer diagnosis were statistically significant at the 0.05 level.

The probability of treatment event occurrence for dental caries/pulp disease was lower in cancer patients. The SHRs were 0.83 and 0.78 within 30 days and 3 months after cancer diagnosis, respectively, with statistical significance at the 0.05 level (95% CI 0.74–0.92 and 0.70–0.86, respectively). The SHR then increased to 1.09 for 1–3 years and was statistically significant at the 0.05 level (95% CI 1.05–1.13).

The SHRs of a treatment event for gingivitis/periodontal disease were 0.80 and 0.75 within 30 days and 3 months after cancer diagnosis, respectively (95% CI 0.74–0.87 and 0.71–0.80, respectively). They gradually increased thereafter, reaching 1.09 after 5 years (95% CI 1.04–1.15). The SHRs were statistically significant at the 0.05 level for all time intervals.

Subgroup analysis by cancer type

The results for the time-dependent SHR of the treatment event for each dental disease by cancer type are presented in Supplementary Figures and Tables (see Additional file 1: Figs. S1–S4 and Additional file 1: Table S4). The probability of stomatitis treatment event occurrence in cancer patients was higher than in the control group for oral and other head and neck cancers, as well as for blood cancer, in the first 3 months after cancer diagnosis, with SHRs exceeding 3.76. The SHRs were 1.71–2.14 in the same period for thyroid and other solid cancers. The SHRs rapidly decreased until 1 year after cancer diagnosis for all cancer types apart from blood cancer, which showed a relatively slight decrease until 3 years.

Unlike the overall trend in treatment events for tooth loss over time, the probability of event occurrence was greater in patients with oral and other head and neck cancers in the first 30-day period after cancer diagnosis, and the SHRs were 1.94 and 5.12, respectively (95% CI 0.65–5.75 and 2.30-11.42, respectively).

The time-dependent SHRs of treatment events for dental caries/pulp disease by cancer type suggested that the magnitude of reduction in treatment events in cancer patients was larger for blood cancer within 3 months after cancer diagnosis. The SHRs were 0.48 and 0.52, with statistical significance at the 0.05 level, before and after 30 days, respectively (95% CI 0.26–0.88 and 0.34–0.79, respectively). However, unlike the overall trend, the probability of event occurrence was significantly higher in patients with other head and neck cancer in the first 30-day period after cancer diagnosis (SHR = 1.71; 95% CI 1.02–2.87).

Similarly to the results for dental caries/pulp disease, the reduction of treatment events for gingivitis/periodontal disease showed a greater magnitude in patients with blood cancer, particularly in the early phase (within 3 months after cancer diagnosis), with SHRs of 0.48 and 0.40 before and after 30 days, respectively (95% CI 0.29–0.78 and 0.27–0.59, respectively). A significantly greater probability of treatment event occurrence was also noted in patients for other head and neck cancer in the first 30-day period after cancer diagnosis (SHR 2.16; 95% CI 1.49–3.11). In addition, the probability was greater in thyroid cancer patients in all time intervals.

Discussion

In this study, for the first time, we compared the proportion of major dental treatment events in cancer patients after the diagnosis of any type of cancer with that in the general population using claims data. The proportion of individuals who received stomatitis treatment was significantly higher in cancer patients, while cancer patients showed significantly lower proportions of treatment event for tooth loss, dental caries/pulp disease, and gingivitis/periodontal disease than the general population. In consideration of the much higher mortality rate in cancer patients and the inappropriateness for censoring the deaths that occurred prior to dental treatment, we conducted a competing risk analysis to calculate adjusted HRs. Since the HRs were not constant over time, we estimated time-dependent SHRs. Stomatitis treatment events were observed to have occurred with a greater probability in cancer patients than in the control group for the entire observation period, while those of other dental treatment events were lower in cancer patients until 3 months after cancer diagnosis and then increased, eventually approaching 1. Some differences in the trends were also observed in the subgroup analysis by types of cancer.

The greater occurrence of treatment events for stomatitis in cancer patients in all time intervals, particularly within 3 months after cancer diagnosis, is probably explained by the fact that stomatitis is managed as a major oral complication of cancer therapy. Pain due to stomatitis was found to be the most prevalent (17%) need requiring dental treatment among cancer patients [21], and a preoperative oral examination is performed when preparing a treatment plan for patients undergoing chemotherapy following surgery to help minimize pain [22]. However, the operative definition used to detect cases of stomatitis in this study was not restricted to cancer-related stomatitis.

Apart from stomatitis, the probability of treatment event occurrence in other major dental diseases was significantly lower in cancer patients within 3 months after cancer diagnosis, and the trend of a lower probability of treatment event occurrence was observed for up to 1 year for tooth loss and gingivitis/periodontal disease. Cancer patients generally experience physical damage due to surgery in the course of cancer treatment, limitations in daily life and social activities due to secondary damage caused by chemotherapy or radiotherapy, and deterioration of physical function [1, 23]. Due to these activity restrictions, the treatment of other chronic diseases is often delayed, which may encompass delays in visits to dental clinics and the treatment of gingivitis and periodontal diseases.

The SHR of treatment events for gingivitis/periodontal disease increased and reached a value greater than 1 after 5 years. A reason for this may be that treatment for periodontal disease, which was neglected during the cancer treatment, was actively attempted after the 5-year period that implies cancer survivorship. Alternatively, this trend may be due to the increased incidence of periodontal disease caused by the progression of dental caries during cancer therapy because of delays in dental treatment.

Oral complications of cancer therapy are associated with oncological treatment modalities, which commonly include surgical resection, chemotherapy, radiotherapy, and hematopoietic stem cell transplantation (HSCT) [2, 10]. These therapies are administered alone or in combination and either cause direct harm to the tissue of oral structures or indirectly damage them through their toxicity. Since the usage of treatment modalities is multifaceted, we explored a subgroup analysis by types of cancer. We first separated blood cancer from the others due to the specific treatment modalities, such as HSCT, used for blood cancer. Head and neck cancers were separately explored from other solid cancers because their anatomical location is close to the oral cavity. We also tried to subdivide head and neck cancers into oral cancer, thyroid cancer, and others since we were initially interested in examining whether the state of dental care in oral cancer patients, who could have direct damage to dental structures during cancer treatment, is different from that of patients with other head and neck cancer, and the categorization of thyroid cancer as a head and neck cancer is disputable [24, 25]. However, differences in tendencies by subtypes of head and neck cancers were not clearly observable, which may have been mainly due to the insufficient number of cases in these subcategories.

A subgroup analysis by cancer type suggested that, unlike the overall trend, the probability of event occurrence for tooth loss was significantly higher in head and neck cancer patients in the early stage after cancer diagnosis. In the course of treating head and neck cancer, extraction tends to be recommended if teeth interfere with the surgical site or the prognosis after radiotherapy is expected to be poor [26], which may be an explanation for this finding. The high incidence of oral complications in patients with head and neck cancer results from the location of the main treatment site. While the probability of stomatitis treatment event occurrence was higher in cancer patients in the early stage after cancer diagnosis for all types of cancer, the probability was particularly higher in patients with head and neck cancer. Stomatitis caused by radiotherapy occurs in 60% of patients with head and neck cancer receiving standard radiotherapy [2].

The number of study subjects varied substantially across different cancer types, resulting in a difference in the precision of the estimations of outcomes by cancer type (see Additional file 1: Table 3). The numbers were less than 1000 for oral cancer and other head and neck cancer, and the confidence intervals obtained in those groups were relatively wide. This was the reason for the non-significance of the SHR of 1.9 for tooth loss treatment in oral cancer patients in the early stage after cancer diagnosis. Nevertheless, the high SHR of 5.1 found in other head and neck cancer patients was still highly significant.

The KNHIS-NSC database was established as a population-based cohort by the National Health Insurance Service (NHIS) of Korea—that is, Korea’s universal coverage health insurance system for all citizens—for the purpose of providing public health researchers and policy makers with a nationally representative sample on all beneficiaries of the NHIS, who comprise more than 97% of the entire Korean population. The one million sample cohort was selected from the target population by systematic stratified random sampling with proportional allocation within strata that were defined based on age group, sex, participants’ eligibility status, and income level. The participants were followed up until the endpoint of the cohort unless their eligibility was disqualified due to death or emigration. The cohort was then refreshed annually during the cohort years by adding a representative sample of newborns across all strata to compensate for the number of subjects who dropped out due to disqualification. The sample’s representativeness was evaluated by examining the sample’s average total annual medical expenses compared to the population average in every stratum and by comparing the cohort with the population according to residence distribution across 16 regions in Korea [27].

Since this study used a national health insurance claims database based on the disease and treatment codes generated after visiting medical institutions, the identified times do not accurately reflect when the disease actually occurred. For example, clinic visits for chronic diseases such as gingivitis/periodontal disease do not necessarily indicate disease occurrence. Besides, cases would be missing if patients did not visit a medical institution for treatment. Such issues are well recognized problems in research using claims data. However, it was not our main intention to evaluate the risk of the disease itself; instead, our outcome of interest was defined as an occurrence of a “treatment event” with a focus on comparing the frequency of major dental treatments received between cancer patients and the general population. The outcome was defined as the occurrence of a treatment event rather than disease to facilitate its interpretation as a consequence that reflects participants’ interest in and prioritization of the treatment of dental disease. Concerning treatment events for tooth loss, a particular event did not refer to an event for treating tooth loss, but instead denoted instances when an extraction treatment was administered when it was needed (i.e., a claim for extraction was made with a disease code indicating a state of tooth loss due to disorders of teeth and supporting structures).

There may be some issues in defining stomatitis, that could be identified by using various categories. We defined stomatitis based on disease codes that included not only recurrent aphthous stomatitis, but also stomatitis by other underlying pathologies such as neutropenic ulcerations, herpetic infections, and candidiasis in the oral area. The national claims data do not expose sensitive diseases such as sexually transmitted diseases to prevent the possibility of identification. Therefore, the codes for herpetic infections and candidiasis would not capture herpes type 2 or candida vaginitis in the data. Nevertheless, the diagnosis may still be considered to have been broadly defined. Therefore, treatment events for stomatitis might have been measured at a higher frequency than the actual incidence in both groups.

The discrepancy between real practice and the records in claims databases is a well-known drawback of the analysis of claims data. The process of constructing data for our analysis, including the selection of subjects, also relied on an examination of disease and treatment codes in the database. Clinicians occasionally input inaccurate codes when filling out insurance claims. For example, in dentistry, it is customary to use “chronic periodontitis” when claiming benefits [14], which may result in overestimation of periodontal disease incidence. However, since this issue would apply equally to cancer patients and the control group, ratios (as a relative measure) are less susceptible to potential bias.

Cancer mortality has decreased by more than 30% over the past 30 years [28], and accordingly, the need for dental treatment for cancer survivors is increasing [29]. In Korea, for instance, 34.8% and 36.6% of cancer survivors suffered from mastication problems and periodontal disease, respectively, and 15.9% needed dentures [30]. However, clinical guidelines for dental care for cancer patients are still insufficient and policy decision-making regarding insurance coverage is needed [30,31,32,33].

Cancer survivors generally experience financial difficulties, and those who reported financial problems were more likely to experience delays in dental and medical treatment [34, 35]. Even in countries where primary and secondary medical care services are supported through a national health insurance system, although the financial burden of cancer treatment is largely covered by the national health insurance system, the allocation of finances for dental care remains neglected [36, 37]. For example, in Korea, cancer patients are subject to a special coverage system according to which they pay only 5% of the total costs of medical care for 5 years after the date of registration as a cancer patient [38]. However, national health insurance coverage applied to only 31.9% of dental treatments in 2015 [39], even though the coverage for certain dental treatments for the elderly has gradually been expanded, including for dental implants [40]. Our study results suggest that cancer patients tend to refrain from dental treatments, implying that consideration should be given to seeking more active and effective means for oral health promotion in cancer patients. One of the potential suggestions could be extending the national health insurance plan to include dental treatment for oral complications from cancer therapy and covering dental care as a part of healthcare management for cancer survivors. Additionally, well-established programs for oral and dental care in patients receiving cancer therapy should be provided to facilitate full information-sharing regarding the need for dental consultations with healthcare professionals and patients. Furthermore, an effective collaboration system between medical doctors and dentists throughout the course of cancer therapy should also be promoted.

Conclusion

Apart from treatments that are associated with cancer therapy, dental treatments in cancer patients are generally delayed. There are several potential reasons for the underdevelopment of dental treatment in cancer patients, in relation to issues in prioritization for cancer therapy over dental treatments as well as the healthcare system. Consideration should be given to seeking more active and effective means for oral health promotion in cancer patients.

Availability of data and materials

Release of the data by the researchers is not permitted. The datasets supporting the findings of this article can only be accessed through the NHISS’ designated network system by any authorized researcher after a formal application to the official website of NHIS data sharing service (https://nhiss.nhis.or.kr/bd/ab/bdaba000eng.do).

Abbreviations

RR:

Relative risk

HR:

Hazard ratio

SHR:

Subdistribution hazard ratio

CI:

Confidence interval

ICD-10:

10th revision of the International Statistical Classification of Diseases and Related Health Problems

KNHIS:

Korean National Health Insurance Service

NHIS:

National Health Insurance Service

IRB:

Institutional Review Board

NHISS:

National Health Insurance Sharing Service

KNHIS-NSC:

Korean National Health Insurance Service-National Sample Cohort

HSCT:

Hematopoietic stem cell transplantation

References

  1. Kim SH. A study on demographic, physical Mental Health, oral Health and Quality of Life in Cancer Patients - the 7th Korea National Health and Nutrition Examination Survey KNHANES VII-3 (2018)-. Korea Acad Industrial Cooperation Soc. 2021;22(1):445–53.

    Google Scholar 

  2. Epstein JB, Thariat J, Bensadoun RJ, Barasch A, Murphy BA, Kolnick L, Popplewell L, Maghami E. Oral complications of cancer and cancer therapy: from cancer treatment to survivorship. CA Cancer J Clin. 2012;62(6):400–22.

    Article  Google Scholar 

  3. Barasch A, Peterson DE. Risk factors for ulcerative oral mucositis in cancer patients: unanswered questions. Oral Oncol. 2003;39(2):91–100.

    Article  Google Scholar 

  4. Choi HS. Reliability and validity of patient self-reported daily questionnaire on oral Mucositis in acute leukemic patients under chemotherapy. J Korean Biol Nurs Sci. 2010;12(3):148–56.

    Google Scholar 

  5. Basile D, Di Nardo P, Corvaja C, Garattini SK, Pelizzari G, Lisanti C, Bortot L, Da Ros L, Bartoletti M, Borghi M et al. Mucosal injury during anti-cancer treatment: from pathobiology to bedside. Cancers (Basel) 2019;11(6).

  6. Elting LS, Cooksley CD, Chambers MS, Garden AS. Risk, outcomes, and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies. Int J Radiat Oncol Biol Phys. 2007;68(4):1110–20.

    Article  Google Scholar 

  7. Palay C. Dental Care: unmet oral needs of patients with Cancer and Survivors. Clin J Oncol Nurs. 2017;21(5):629–32.

    Article  Google Scholar 

  8. Duncan GG, Epstein JB, Tu D, El Sayed S, Bezjak A, Ottaway J, Pater J, National Cancer Institute of Canada Clinical Trials G. Quality of life, mucositis, and xerostomia from radiotherapy for head and neck cancers: a report from the NCIC CTG HN2 randomized trial of an antimicrobial lozenge to prevent mucositis. Head Neck. 2005;27(5):421–8.

    Article  Google Scholar 

  9. Lalla RV, Treister N, Sollecito T, Schmidt B, Patton LL, Mohammadi K, Hodges JS, Brennan MT. OraRad Study G: oral complications at 6 months after radiation therapy for head and neck cancer. Oral Dis. 2017;23(8):1134–43.

    Article  Google Scholar 

  10. Sroussi HY, Epstein JB, Bensadoun RJ, Saunders DP, Lalla RV, Migliorati CA, Heaivilin N, Zumsteg ZS. Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis. Cancer Med. 2017;6(12):2918–31.

    Article  Google Scholar 

  11. Sohn HO, Park EY, Jung YS, Lee EK, Lee HK, Kim EK. A study on oral health-related quality of life following radiotherapy in patients with head and neck cancer. J Korean Acad Oral Health. 2017;41(2):110–5.

    Article  Google Scholar 

  12. Badr H, Rosenthal DI, Milbury K, Garden AS, Frank SJ, Gunn GB, Cleeland CS, Gritz ER. Do the treatment outcome priorities of head and neck cancer patients change after undergoing radiation treatment? J Clin Oncol. 2010;28(15suppl):5599–9.

    Article  Google Scholar 

  13. Cuschieri S. The STROBE guidelines. Saudi J Anaesth. 2019;13(Suppl 1):31–S34.

    Article  Google Scholar 

  14. Yoo JJ, Kim DW, Kim MY, Kim YT, Yoon JH. The effect of diabetes on tooth loss caused by periodontal disease: a nationwide population-based cohort study in South Korea. J Periodontol. 2019;90(6):576–83.

    Article  Google Scholar 

  15. Yoo JJ, Yoon JH, Kang MJ, Kim M, Oh N. The effect of missing teeth on dementia in older people: a nationwide population-based cohort study in South Korea. BMC Oral Health. 2019;19(1):61.

    Article  Google Scholar 

  16. Kim JH, Kweon HI, Lee JS, Choi JK, Kim DW, Choi SH. Evaluation of national health insurance coverage of periodontal scaling: a nationwide cohort study in Korea. Korean Dent Association vol. 2016;54:604–12.

    Google Scholar 

  17. Service HIRaA. Health Insurance Medical Care. Health Insurance Review and Assessment Service; 2021.

  18. Therneau TM, Grambsch PM. The cox model. Modeling survival data: extending the Cox model.edn.: Springer; 2000:pp. 39–77.

  19. Austin PC, Latouche A, Fine JP. A review of the use of time-varying covariates in the Fine-Gray subdistribution hazard competing risk regression model. Stat Med. 2020;39(2):103–13.

    Article  Google Scholar 

  20. R: A language and environment for statistical computing. https://www.R-project.org/

  21. de Oliveira MCQ, Lebre Martins BNF, Santos-Silva AR, Rivera C, Vargas PA, Lopes MA, Vechiato-Filho AJ, Brandao TB, Prado-Ribeiro AC. Dental treatment needs in hospitalized cancer patients: a retrospective cohort study. Support Care Cancer. 2020;28(7):3451–7.

    Article  Google Scholar 

  22. Levi LE, Lalla RV. Dental Treatment Planning for the patient with oral Cancer. Dent Clin North Am. 2018;62(1):121–30.

    Article  Google Scholar 

  23. Fischer DJ, Epstein JB, Yao Y, Wilkie DJ. Oral health conditions affect functional and social activities of terminally ill cancer patients. Support Care Cancer. 2014;22(3):803–10.

    Article  Google Scholar 

  24. Wu KH. The management of head and neck cancer. Surg (Oxford). 2009;27(12):540–5.

    Article  Google Scholar 

  25. Chow LQM. Head and Neck Cancer. N Engl J Med. 2020;382(1):60–72.

    Article  Google Scholar 

  26. Clough S, Burke M, Daly B, Scambler S. The impact of pre-radiotherapy dental extractions on head and neck cancer patients: a qualitative study. Br Dent J. 2018;225(1):28–32.

    Article  Google Scholar 

  27. Lee JY, Lee JS, Park SH, Shin SA, Kim KW. Cohort Profile: the National Health Insurance Service–National Sample Cohort (NHIS-NSC). Int J Epidemiol. 2017;46(2):e15.

    Google Scholar 

  28. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33.

    Article  Google Scholar 

  29. Weaver KE, Rowland JH, Bellizzi KM, Aziz NM. Forgoing medical care because of cost: assessing disparities in healthcare access among cancer survivors living in the United States. Cancer. 2010;116(14):3493–504.

    Article  Google Scholar 

  30. Han MA. Oral health status and behavior among cancer survivors in Korea using nationwide survey. Int J Environ Res Public Health. 2017;15(1).

  31. Epstein JB, Parker IR, Epstein MS, Stevenson-Moore P. Cancer-related oral health care services and resources: a survey of oral and dental care in canadian cancer centres. J Can Dent Assoc. 2004;70(5):302–4.

    Google Scholar 

  32. Rocke J, McLaren O, Hardman J, Garas G, Smith ME, Ishii H, Constable J, Tikka T, Wie Liu Z, Williams R, et al. The role of allied healthcare professionals in head and neck cancer surveillance: a systematic review. Clin Otolaryngol. 2020;45(1):83–98.

    Article  Google Scholar 

  33. McGuire DB. Mucosal tissue injury in cancer therapy. More than muscositis and mouthwash. Cancer Pract. 2002;10(4):179–91.

    Article  Google Scholar 

  34. Kent EE, Forsythe LP, Yabroff KR, Weaver KE, de Moor JS, Rodriguez JL, Rowland JH. Are survivors who report cancer-related financial problems more likely to forgo or delay medical care? Cancer. 2013;119(20):3710–7.

    Article  Google Scholar 

  35. Kim SY, Lim SA. Factors Associated with Unmet Dental Care needs among korean Adult Cancer Survivors: cross-sectional analysis of the 2016–2018 KNHANES. Healthc (Basel). 2022;10(8):1563.

    Article  Google Scholar 

  36. Palm W, Webb E, Hernandez-Quevedo C, Scarpetti G, Lessof S, Siciliani L, van Ginneken E. Gaps in coverage and access in the European Union. Health Policy. 2021;125(3):341–50.

    Article  Google Scholar 

  37. Hunter J, Smith C, Delaney GP, Templeman K, Grant S, Ussher JM. Coverage of cancer services in Australia and providers’ views on service gaps: findings from a national cross-sectional survey. BMC Cancer. 2019;19(1):570.

    Article  Google Scholar 

  38. Kim SJ, Kwon SM. Effect of expanding benefit coverage for cancer patients on equity in health care utilization and catastrophic expenditure. Health Policy Manag. 2014. 24;228–41.

  39. Lee MY, Yang DN. Recognition of dental patients in the capital area with regard to the private dental insurance. J Korean Soc Oral Health Sci. 2018;6:15–22.

    Google Scholar 

  40. Shin H, Cho HA, Kim BR. Dental Expenditure by Household Income in Korea over the Period 2008–2017: A Review of the National Dental Insurance Reform. Int J Environ Res Public Health 2021;18(8).

Download references

Acknowledgements

Not applicable.

Funding

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (Grant No.: HI19C1178) and by a grant of the National Research Foundation of Korea (Grant No.: 2022R1A2C101043711). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

Authors

Contributions

SH and H-KP conceived the idea. SH, H-KP, E-GP, AH and J-HY designed the study. AH and E-GP conducted data acquisition. AH and E-GP analyzed the results. SH, H-KP, AH, E-GP, J-HY and J-YC interpreted results. AH and SH drafted the manuscript and AH prepared figures and tables. SH and H-KP acquired study funding. All authors reviewed and approved the manuscript.

Corresponding authors

Correspondence to Hee-Kyung Park or Seokyung Hahn.

Ethics declarations

Ethics approval and consent to participate

The study protocol was approved by the Institutional Review Board (IRB) of Seoul National University College of Medicine/Seoul National University Hospital, Korea (approval no.: E-1911-012-1076). All methods were performed in accordance with the relevant guidelines and regulations approved by the IRB. The requirement for informed consent was exempted by the IRB of Seoul National University College of Medicine/Seoul National University Hospital, Korea since the KNHIS-NSC dataset comprises de-identified secondary data for research purposes in a fully anonymized form. Restricted access to the database for the study purpose was authorized by the National Health Insurance Sharing Service (NHISS) in Korea (Research Management No.: NHIS-2020-2-144).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1:

Supplementary tables and figures.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Han, A., Park, EG., Yoon, JH. et al. A time-dependent subdistribution hazard model for major dental treatment events in cancer patients: a nationwide cohort study. BMC Oral Health 23, 64 (2023). https://doi.org/10.1186/s12903-023-02723-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12903-023-02723-7

Keywords