Oral functional impairment may cause malnutrition following oral cancer treatment in a single-center cross-sectional study

Oral dysfunction and dysphagia after oral cancer treatment are linked to altered nutritional status. We aimed to identify specific oral functions related to nutritional status. We conducted a cross-sectional study from September 2019 to December 2021, recruited 75 participants (median age: 72.0 years), including 52 males and 23 females, collected background data, and evaluated oral function. The Mini Nutritional Assessment-Short Form (MNA-SF) scores were divided into three groups (normal nutritional status, at risk of malnutrition, and malnourished), and a multi-group comparison was conducted for each oral function measurement (microorganisms, oral dryness, occlusal force, tongue pressure, masticatory function, and Eating Assessment Tool [EAT-10]). The primary tumor site was the tongue in 31 patients (41.3%), gingiva in 30 (40.0%), and others in 14 (18.7%). Multiple comparisons revealed significant differences in occlusal force, tongue pressure, masticatory function, and EAT-10 levels, categorized as Type I (Transport type) and Type III (Occlusion type) postoperative oral dysfunctions, between each MNA-SF group. Multiple regression analysis showed a statistically significant association with MNA-SF in terms of masticatory function and EAT-10 levels, categorized as Type I. Type I and Type III are risk factors for malnutrition, confirming that different types of postoperative oral dysfunction require unique nutritional guidance.

conceptual disorder that affects both Stage I and Stage II transport. Type II (Oral hygiene type) consists of items related to bacterial counts, oral health perception, and oral dryness.
Oral dryness has been reported to be an accelerator for an increased number of oral microorganisms due to the decreased rate of salivary flow 12,13 . A decreased rate of salivary flow has been reported to be a risk factor for periodontal disease and dental caries 14 . Tooth loss due to these common dental diseases can lead to decreased masticatory and swallowing function, possibly leading to malnutrition 15,16 . Type III (Occlusal type) consists of occlusal force alone. This component is thought to be an independent component because its elements are very different from those of other components 11 . Therefore, recent studies have clarified the details of postoperative oral function following evidence-based oral cancer treatment guided by the NCCN guidelines 3 .
However, there are still some problems with nutritional instructions for oral cancer patients. Although there are reports that early intervention by a dietitian may improve the nutritional status of patients with oral cancer, two randomized controlled trials could not confirm the effectiveness of this intervention 17,18 . Therefore, we hypothesized that different types of postoperative oral dysfunction require different nutritional guidance and conducted a study to clarify the relationship between various postoperative oral functions and nutritional status. It is assumed (null hypothesis H0) that Type I-III oral dysfunctions are not associated with nutritional status.

Methods
Data collection. Participants in this cross-sectional study were enrolled according to the following criteria: (1) patients diagnosed and treated for oral squamous cell carcinoma based on NCCN guidelines by a single surgical team in a single center; (2) patients who visited the Department of Oral and Maxillofacial Surgery/ Oral Care Center at Shimane University Hospital (Shimane, Japan); (3) patients aged 20 years or older; and (4) patients who could understand the questions and answer the questionnaire. Participants were excluded according to the following criteria: (1) cases of recurrent or metastatic oral cancer and (2) cases of drop-out due to death from perioperative complications 3 . All data were collected just before the patient was discharged from the hospital. All treatments were performed at the hospital, and the time of discharge was defined as the point at which the attending physicians judged, based on the treatment workup and course according to the Japanese medical insurance system after definitive oral cancer treatment guided by the NCCN guideline, that there were no systemic or local complications and that the patient could reintegrate into social activities and life. The study period lasted from September 2019 to December 2021, and data were collected using a sequential sampling method. This study was approved by the Institutional Review Board of the Ethics Committee of the Shimane University Faculty of Medicine (approval number: 4041) on September 30, 2019. Also, all methods were performed in accordance with Declarations of Helsinki. Written informed consent was obtained from each participant prior to participation in the study.
Background data. We sampled the following variables as background data: sex, age (years), body mass index (BMI, kg/m 2 ), alcohol consumption (regular drinker or not), Brinkman index, Eastern Cooperative Oncology Group performance status, primary tumor site, cancer stage based on the criteria of the Union for International Cancer Control (version 8), treatment methods (surgery/surgery and adjuvant radiotherapy/surgery and adjuvant chemoradiotherapy), presence of neck dissection, presence of reconstructive surgery, and number of teeth. Pull back motion of food from the anterior region of the mouth to the molar region.

Processing:
Mastication and mix triturated food with saliva. Stage II transport: Squeeze back movement of the processed food from mouth to pharynx.

HTT (Hypopharyngeal transit time):
Transition of the food at hypopharynx.

Esophageal:
Peristaltic movement of esophagus. www.nature.com/scientificreports/ Oral function measurement. The method recommended by the Japanese Society of Gerodontology in its position paper was adopted to measure oral function 19 . However, tongue-lip motor function could not be assessed in patients with tongue defects caused by oral cancer treatment; therefore, it was removed from the assessment items.
Microorganisms. The number of microorganisms was measured by collecting samples from the center of the tongue dorsum using a rapid oral detection apparatus (Bacterial counter; Panasonic Healthcare, Tokyo, Japan). The number of microorganisms indicated by the bacterial counter and the grade were recorded.
Oral dryness. Oral dryness was measured using an oral moisture checker (Mucus; Life, Saitama, Japan), and the median of three measurements on the dorsum of the tongue was taken as the data. Measurements were taken on the healthy side if there was a reconstructed flap due to a defect in the tongue, and in the middle of the flap if a total resection had been performed.
Occlusal force. The occlusal force was measured using a pressure-sensitive paper (Dental Prescale Occluzer; GC, Tokyo, Japan) by clenching for 3 s at the intercuspal position. If the subject had a denture, the occlusal force was measured with the denture in place.
Tongue pressure. Tongue pressure was measured at the center of the dorsum of the tongue using a tongue pressure measuring instrument (TPM-01; JMS, Hiroshima, Japan).
Masticatory function. Masticatory function was measured using a masticatory ability testing system (Gluco Sensor GS-II; GC, Tokyo, Japan).
EAT-10. Swallowing function was assessed using a 10-question questionnaire measured on a 5-point Likert scale (0 = no problem; 4 = severe problem) developed by Belafsky in 2008 20 . The EAT-10 has a maximum total score of 40, with higher scores indicating poor swallowing function.

Swallowing function measurement.
Functional oral intake scale. The functional oral intake scale (FOIS) has a maximum total score of 40, with higher scores indicating poor swallowing function 21 .

Mini Nutritional Assessment-Short Form. Nutritional status was assessed using the Mini Nutritional
Assessment-Short Form (MNA-SF), which consists of six items with a maximum score of 14 and a minimum score of 0 22 . The MNA-SF scores can also be classified into three groups (normal nutritional status [scores [12][13][14], at risk of malnutrition [scores [8][9][10][11], and malnourished [scores 0-7]).
Matsuda-Kanno classification. The Matsuda-Kanno classification was used as a reference for classifying postoperative oral dysfunctions. The classification can be divided into three types: transport, Oral hygiene, and Occlusal. In this study, the cut-off values of each oral function measurement were used as references (Table 1) Table 3. There were significant differences in age (p = 0.025), body mass index (p = 0.001), number of teeth (p = 0.020), performance status (p = 0.005), tumor stage (p < 0.042) and treatment methods (surgery/surgery and adjuvant radiotherapy/surgery and adjuvant chemoradiotherapy; p < 0.001).
Multiple group comparisons of MNA-SF scores and oral function measurements. Multiple group comparisons of MNA-SF scores and oral function measurements are shown in Fig. 2. There were significant differences in occlusal force, tongue pressure, masticatory function, and EAT-10 levels.

Discussion
The major finding of this study is that multiple oral dysfunctions have an impact on nutritional status. Of these, masticatory function and EAT-10 levels were found to be independent and distinct oral dysfunctions in our previous studies 11 . In addition, the EAT-10 swallowing assessment has traditionally been associated with nutritional status in healthy individuals 23 . This disproved our null hypothesis and the alternative hypothesis was adopted. Our hypothesis that "different types of postoperative oral dysfunction require different nutritional guidance" is likely to be correct, and our results were reasonable. In other words, the Type I (Transport type) and III (Occlusion type) hypotheses were accepted, but the Type II (Oral hygiene type) oral dysfunction hypothesis was rejected. Masticatory function and EAT-10 constitute Type I. Arthur et al. reported that there was no relationship between masticatory function and nutritional status, but this may be due to the fact that the assessment items were the number of teeth and occluding pairs of teeth, rather than masticatory function, which is the ability to pull back food from the anterior region of the mouth to the molar region and squeeze back processed food from the mouth to the pharynx 24 . Therefore, based on the results of our study, we believe that masticatory function is related to postoperative nutritional status. Since it is well known that tongue pressure and masticatory function decrease with resection, especially in patients with oral cancer, our results also support the results of previous studies 25, 26 . In addition, a cross-sectional study of 909 hospitalized patients showed an association between EAT-10 levels and nutritional status, and the results of this study were similar 27 . Therefore, malnutrition may occur due to Type I. In the nutritional instructions for Type I, it is especially important to choose a food texture that facilitates the formation of boluses, which can be transported to the pharynx by gravity 28 . In addition, the use of palatal augmentation prosthesis as a patient specific oral-maxillofacial prosthetic treatment makes it easier to direct the bolus into the esophagus, and rehabilitation with maneuvers on swallowing function is a reinstatement of safe oral intake 29,30 .
In contrast, multivariate analysis did not show a significant association between occlusal force and nutritional status, but occlusal force was the only component of Type III, suggesting the possibility of nutritional impairment caused by Type III. Decreased occlusal force is mainly caused by resection of the masticatory muscles (temporalis, masseter, lateral pterygoid, and medial pterygoid muscles) and loss of occluding pairs of teeth due to maxillary or mandibular resection 31 . This study is the first to show that maxillary and mandibular deficiencies can reduce occlusal force and affect nutritional status, while also suggesting that oral-maxillofacial prosthetic treatment may be useful. The first-line treatment for patients with maxillary or mandibular defects is patient-specific oral-maxillofacial prosthetic treatment using dentures and dental implants 32 . However, prosthetic treatment has some limitations, and even with dental implants, it is unlikely that the occlusal force will be restored to what it was before resection 33 . Decreased occlusal force is mainly associated with decreased intake of vegetables and proteins, suggesting that nutritional guidance should pay more attention to the loss of food diversity than food texture 34 . In addition, since regular and longitudinal dental visits are important for oral-maxillofacial prosthetic management and care, community collaboration is also important from the perspective of long-term nutritional management following oral cancer treatment 35 .
The results of the trend test suggested that malnutrition caused by the Type I and Type III described above may be exacerbated in stages. In other words, in clinical practice, we should not only focus on the presence of malnutrition, but also screen and intervene earlier for patients in the pre-malnutrition or intermediate stages of malnutrition using a multidisciplinary team approach 36 .
We can consider several limitations to our study, the main ones being its retrospective nature and small sample size due to the study period and its single-center design 37  www.nature.com/scientificreports/   be classified as explanatory variables, only rough adjustment for confounders was conducted for tumor site and treatment. In addition, sub-group analysis was not conducted. However, since postoperative oral dysfunction and dysphagia have been reported to occur in both single and multimodal treatments, it was assumed that an analysis considering more confounding factors would yield results similar to those of this study 38 . Further, because many patients in this study had advanced oral cancer, the prevalence of malnutrition due to postoperative oral dysfunction may need to be estimated lower when considering generalizability 39 . However, since the number of severely ill patients is expected to increase in Japan, where the population is super-aging, the generalizability of this study is likely to be high in developed countries with aging populations 40 . Future studies should evaluate whether malnutrition is reversible over time because the preoperative oral function and the long-term prognosis for postoperative oral function are unclear.

Conclusion
Decreased masticatory function and EAT-10 levels are risk factors for malnutrition. Postoperative oral dysfunction Type I (Transport type) may be a risk factor for nutritional status in patients treated for oral cancer. Further, individual nutritional guidance may be adapted to each type of postoperative oral dysfunction. www.nature.com/scientificreports/

Data availability
The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.