Salivary gland function, development, and regeneration.

Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological function of salivary glands, as well as how they are affected by disease and injury, will direct the development of therapy to repair and regenerate them. Significant recent advances, particularly in the OMICS field, increase our understanding of how salivary glands develop at the cellular, molecular, and genetic levels: the signaling pathways involved, the dynamics of progenitor cell lineages in development, homeostasis, and regeneration, and the role of the extracellular matrix microenvironment. These provide a template for cell and gene therapies as well as bioengineering approaches to repair or regenerate salivary function.

Comparisons of Non-Oral Immune-Related Adverse Events Among Patients With Cancer With Different Oral Toxicity Profiles.

OBJECTIVES: Immune-related adverse events (irAEs) are common. Oral irAEs tend to cluster in patients who experience concurrent toxicities. We aimed to characterize the frequency and trajectory of non-oral irAEs in patients who developed oral irAEs, assess their relationship with non-oral irAEs, and compare those characteristics with patients without oral irAEs. METHODS: A retrospective chart review was conducted to identify patients who started ICIT between December 11, 2011, and September 15, 2019 (n = 4683) in the Mass General Brigham Registered Patient Data Registry. Demographic information, cancer diagnosis, ICIT regimen, treatment duration, and time and number of infusions to irAE onset were recorded. Non-oral irAEs were categorized into 13 groups. Patients with melanoma, pulmonary cancer, or head and neck cancer who had oral irAEs were then matched with those without oral irAEs to compare the prevalence of concomitant non-oral irAEs. RESULTS: Three hundred and fourteen patients with oral irAEs with a mean age of 65.9 ±â€…12.6 years (43.3% females) were included. Patients with multiple oral irAEs were more likely to have non-oral irAEs (OR: 2.7, 95% CI, 1.3-3.5), including cutaneous (OR: 1.7, 95% CI, 1.1-3.0), rheumatological (OR: 2.2, 95% CI, 1.1-4.2), thyroid (OR: 2.4, 95% CI, 1.2-4.9), and neurological irAEs (OR: 2.5, 95% CI, 1.0-6.3). Compared to matched patients with non-oral irAEs, patients with oral irAEs were more likely to have cutaneous (OR: 1.7, 95% CI, 1.0-2.8) and thyroid (OR: 2.86, 95% CI, 1.1-7.5) irAEs. The development of oral and non-oral irAEs is often coincidental. CONCLUSION: Patients who have non-oral irAEs should be monitored for development of oral irAEs for prompt management.

PIEZO1 activation may serve as an early tissue biomarker for the prediction of irradiation-induced salivary gland dysfunction.

Irradiation (IR)-induced xerostomia is the most common side effect of radiation therapy in patients with head and neck cancer (HNC). Xerostomia diagnosis is mainly based on the patient's medical history and symptoms. Currently, no direct biomarkers are available for the early prediction of IR-induced xerostomia. Here, we identified PIEZO1 as a novel predictive tissue biomarker for xerostomia. Our data demonstrate that PIEZO1 is significantly upregulated at the gene and protein levels during IR-induced salivary gland (SG) hypofunction. Notably, PIEZO1 upregulation coincided with that of inflammatory (F4/80) and fibrotic markers (fibronectin and collagen fibers accumulation). These findings suggest that PIEZO1 upregulation in SG tissue may serve as a novel predictive marker for IR-induced xerostomia.

A new approach to prevent radiation-induced xerostomia using intraglandular injection of mitochondria-boosting agents.

Radiotherapy in patients with head and neck cancer fairly leads to xerostomia, profoundly affecting their quality of life. With limited effective preventive and therapeutic methods, attention has turned to exploring alternatives. This article outlines how intraglandular injection of mitochondria-boosting agents can serve as a potential strategy to reduce salivary acinar damage. This method can contribute to the thoughtful development of study protocols or medications to reduce radiation-induced salivary glands damage.

Long-term follow-up of protective effects on salivary and swallowing structures and improvement of late xerostomia and dysphagia by level IIb optimisation in clinical target volume of nasopharyngeal carcinoma.

BACKGROUND: This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC). METHODS: Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan-Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses. RESULTS: Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (Dmean) and V26 of parotid glands; Dmean and V39 of submandibular glands; and Dmean of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The Dmean of the parotid and sublingual glands was a risk factor for xerostomia. The Dmean of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia. CONCLUSIONS: Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival.

Therapy-Associated Saliva and Taste change Evaluation (TASTE) in head & neck cancer patients undergoing radiotherapy: a study protocol.

BACKGROUND: One of the main side effects of radiation therapy to the head and neck region is altered taste sensation. This causes significant morbidity and has profound effects on the quality of life (QoL) of patients. While radiation-associated toxicities like xerostomia and dysphagia are part of large investigations, data on taste impairment is sparse. Small cohort sizes in the majority of studies and a variety of analysis methods limit our current understanding of the underlying processes. None of the studies published to date used a taste-specific QoL questionnaire with differentiation of the different taste qualities (e.g. sour, bitter). Furthermore, data regarding the correlation of taste impairment with radiation-associated change in saliva composition is currently not available. The aim of the TASTE study is to fill this gap. Based on the acquired data, a normal tissue complication probability (NTCP) model for late radiation-associated taste impairment will be developed. METHODS: In this prospective, observational multicenter study 150 head and neck cancer patients undergoing radiation therapy will be recruited and undergo repetitive (semi-) objective and subjective assessment of their taste, smell and salivary function (questionnaires, taste and smell assessment, saliva analysis). Primary endpoint will be patient-reported taste impairment 12 months post radiation therapy using a standardized questionnaire. Secondary endpoints will include taste impairment measured using taste strips at 12 months and 2 years post radiation therapy. Differences between subgroups (radiation side, chemotherapy, etc.) and changes over time will be assessed while adjusting for confounding factors (e.g. age, sex, smoking history). DISCUSSION: This study sets out to further our understanding of taste impairment in patients undergoing radiation therapy to the head and neck region with the goal to prevent this common side effect in future patients. The results of the study may be used to evaluate taste-preserving radiotherapy for patients with head and neck cancer, which may significantly reduce the long-term burden in this patient cohort.

Xerostomia and Salivary Dysfunction in Patients With Diabetes Mellitus. A Cross-Sectional Study.

BACKGROUND: Diabetes mellitus (DM) has been associated with salivary disorders such as xerostomia and hyposalivation. The aim of this study was to determine the prevalence of these disorders and their risk factors in DM patients. METHODS: DM patients from two health centers were included. Epidemiological and DM control-related variables were collected. Xerostomia Inventory was filled out by the patients and unstimulated whole salivary flow was collected. Logistic regression tests were performed. RESULTS: A total of 168 patients were included (46.4% men, 53.6% women, mean age 72.54 [SD 11.03 years]). Thirteen patients had Type 1 DM and 155 had Type 2 DM. 52.4% experienced xerostomia and 41.1% had unstimulated whole salivary flow hyposalivation. Women were more likely to suffer hyposalivation than men (OR 2.5, 95% CI 1.32-4.73; p = 0.005). Patients with T2DM were less likely to suffer UWS hyposalivation than T1DM patients (OR 0.28, 95% CI 0.08-0.95; p = 0.04). Glycemic control was not significantly worse in patients with xerostomia and hyposalivation. The drugs for the treatment of DM were not associated with salivary disorders. However, some drugs to treat other comorbidities such hypertension and neurological diseases were associated with xerostomia and hyposalivation. CONCLUSIONS: The prevalence of xerostomia and unstimulated whole salivary flow hyposalivation in patients with DM is high. Female sex, T1DM, and the use of certain non-antidiabetic drugs increased the risk of suffering these disorders. The possible association between DM, xerostomia, and/or hyposalivation is complex and may be influenced by multiple factors. Therefore, further studies are needed to evaluate whether DM influences these salivary disorders.

MASCC/ISOO Clinical Practice Statement: Clinical assessment of salivary gland hypofunction and xerostomia in cancer patients.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the clinical assessment of salivary gland hypofunction and xerostomia in cancer patients. METHODS: This CPS was developed based on a critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and tables to generate a short manual about the best standard of care. RESULTS: The objective assessment of saliva secretion involves an extra- and intra-oral clinical examination while the subjective assessment involves eliciting information on the patient's complaint of xerostomia and its impact on daily functioning. This CPS summarizes the common investigator- and patient-reported instruments used in clinical practice for assessing salivary gland hypofunction and xerostomia in cancer patients. CONCLUSION: There is a range of tools to assess salivary gland function in patients undergoing cancer therapy, patients recovering from cancer therapy, or cancer survivors. Clinicians should ideally conduct both objective and subjective measurements to ensure a clear understanding about the status of the patients in order to provide the most appropriate treatment.

MASCC/ISOO Clinical Practice Statement: Management of salivary gland hypofunction and xerostomia in cancer patients.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the management of salivary gland hypofunction and xerostomia in cancer patients. METHODS: This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and tables to generate a short manual about the best standard of care. RESULTS: Salivary gland hypofunction and xerostomia in cancer patients are managed by (i) stimulating saliva production of salivary glands with residual secretory capacity or (ii) artificial wetting of the oral and lip surfaces which can be achieved by pharmacological or non-pharmacological interventions. Pharmacological interventions encompass the use of sialagogues and sialolytics, while non-pharmacological interventions involve the use of moistening agents, mechanical, gustatory, or electrostimulation of the salivary glands. Additional treatment modalities may be incorporated in practice based on local availability and the clinician's experience. CONCLUSION: The information presented in this CPS offers clinicians convenient access to the dosages and regimens of different interventions for managing salivary gland hypofunction or xerostomia to facilitate clinical efficiency and conserve valuable time for clinicians.

Impact of low-level laser therapy on the quality of life of patients with xerostomia undergoing head and neck radiotherapy: a systematic review.

PURPOSE: To carry out a systematic review to assess whether low-level laser therapy can improve the quality of life of patients with xerostomia undergoing head and neck radiotherapy. METHODS: A systematic search was performed through Embase, Medline/PubMed, Cochrane, Scopus, Web of Science, nonpeer-reviewed clinicaltrials.gov and LILACS. The strategy included clinical studies were selected that prospectively followed or evaluated the quality of life by directly comparing the use of low-level laser therapy for xerostomia induced by head and neck radiotherapy with alternative therapies without the use of a laser. The risk of bias in the studies was assessed by RoB 2.0 and Robins I. RESULTS: After all application of the predetermined criteria, four studies were included, dated between the years 2014 and 2023. Three studies described as randomized clinical trials were included, one of which was a randomized pilot study and only one was a prospective clinical trial. A total of 126 patients were evaluated, all four studies used the infrared wavelength, with two studies using the combination with the red wavelength. It was observed that low-level laser therapy can change the sensation of dry mouth, improving patients' quality of life. In addition, changes related to increased stimulated and unstimulated salivary flow were also identified. CONCLUSION: The use of low-level laser therapy has promising results on xerostomia, consequently improving the quality of life of patients undergoing radiotherapy in the head and neck region.

Radiation-induced xerostomia and cariogenic dietary habits.

PURPOSE: Despite the availability of various prevention methods, dental caries continue to be diagnosed in patients receiving head and neck radiotherapy (RT). Since conventional approaches do not evaluate posttreatment alterations in dietary behaviors, we aimed to assess the influence of radiation-induced xerostomia on post-RT cariogenic dietary habits in patients. METHODS: Fifty-seven patients completed the Xerostomia Questionnaire (XQ) and answered questions regarding daily cariogenic food and beverage (CFB) intake, daily tooth brushing, fluoride application, and subjective total taste acuity (STTA). They also underwent evaluations to determine the Simplified Oral Hygiene Index (OHI-S) score, Saxon test score, number of decayed-missing-filled teeth (DMFT), and proportion of DMFT to the test teeth (DMFT rate). Clinical records were searched for information regarding RT modalities, including the median of the mean dose to the parotid glands, days after the completion of RT, submandibular gland resection, whole-neck irradiation, and the DMFT value and rate before RT. The patients were divided into low and high XQ score groups based on the median XQ score of 47.5 for the two sample tests. Univariable and multivariable regression analyses were used to identify independent factors for frequent CFB intake. RESULTS: Higher XQ scores were associated with a significantly greater frequency of CFB intake (p = 0.028*). Regression analysis also identified a higher XQ score (p = 0.017*) as an independent risk factor for frequent CFB intake. CONCLUSION: Radiation-induced xerostomia increased the frequency of CFB intake.

Self-perceived oral health in hemato-oncological patients and the relation to quality of life.

PURPOSE: To assess the self-reported oral health and oral health-related quality of life of patients diagnosed with hemato-oncological disease. PATIENTS AND METHODS: Data was collected through a digital questionnaire in collaboration with the Dutch patient organization Hematon. The questionnaires EORTC-QLQ-C30, EORTC-QLQ-OH15, shortened Xerostomia Inventory (XI), and the OHIP-14 were used. RESULTS: Seven hundred five patients were included (52.5% female, mean age 63.2 ± 10.1). The majority was diagnosed more than 2 years ago (86%) and had received treatment (81%) for their disease. Lymphoma, leukemia, and multiple myeloma were the most frequent malignancies. Chemotherapy alone, chemotherapy in combination with targeted therapy or immunotherapy, and myeloablative chemotherapy followed by autologous stem cell transplantation were the most common treatment modalities. The XI identified that 40.5% met the criteria for xerostomia. Other complaints included mouth soreness and sensitivity, gingival pain and bleeding, problems with teeth or with an ill-fitting denture. Despite reporting oral complaints, most patients experienced a rather good OH-QoL. A high xerostomia score led to a significantly lower OH-QoL. Female gender, history of stem cell transplantation, radiation to head and neck, and multiple daily medication use were significant predictors of xerostomia. CONCLUSION: Patients with hematologic malignancies frequently reported a dry mouth and other oral complaints including mouth soreness and sensitivity, gingival pain and bleeding, and problems with teeth. Despite these oral complaints, most patients experienced a relatively good OH-QoL. Future longitudinal studies are needed, and health professionals should have an active role in providing oral supportive care based on patients' individual needs.

Salivary, lacrimal and nasal (SALANS) measure to assess side effects following radioactive iodine treatment: development, psychometric properties, and factor structure.

PURPOSE: This study aimed to develop and psychometrically evaluate a patient-reported outcome measure (PROM), SAlivary, LAcrimal, NaSal (SALANS), to document patients' symptoms after radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC). METHODS: We generated and iteratively revised SALANS items based on expert input, focus group discussions and feedback from cognitive testing (n = 17). We administered an initial SALANS measure with 39 items to patients diagnosed with DTC in the past two years (n = 105). Exploratory factor analysis (EFA) examined the factor structure of the SALANS items. We assessed the consistency reliability and related the total and subscale scores of the final SALANS to existing PROMs to assess validity. RESULTS: The final SALANS consisted of 33 items and six subscales (sialadenitis, taste, xerostomia, dry eyes, epiphora, and nasal) with six factors extracted by EFA. The six subscales demonstrated good internal reliability (α range = 0.87-0.92). The SALANS total score showed good convergent validity with the Xerostomia Inventory (r = 0.86) and good discriminant validity with a measure of spirituality (r = - 0.05). The mean SALANS total score was significantly higher (d = 0.5, p < 0.04) among patients who had RAI compared to those who did not have RAI. CONCLUSION: Preliminary evidence suggests that SALANS is a novel and reliable PROM to assess the type and frequency all symptoms experienced after RAI treatment for DTC. Future work is needed to further validate and develop the scale.

Use of the modified Schirmer test to measure salivary gland hypofunction/hyposalivation: Systematic review and meta-analysis.

Although dry mouth is a relatively common condition, salivary flow is not routinely measured in dental clinical practice. Moreover, existing data regarding the use of the modified Schirmer test (MST) for the screening of dry mouth has not been summarized. This systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, aimed to determine whether the modified Schirmer test can be used to identify dry mouth. The databases of PubMed, Scopus, ScienceDirect, and CENTRAL (CRD42023393843) were systematically searched to retrieve articles published until 9th November 2023. Among the 343 original articles retrieved, six met the inclusion criteria. A total of 1150 patients, comprising 710 (61.7%) women and 440 (38.3%) men (mean age, 47.1 ± 7.3 years), were included. The meta-analysis revealed a weak correlation coefficient of r ¯ $\bar{r}$  = 0.42 (95% Cl: 0.29-0.55) between MST and the unstimulated salivary flow rate. Therefore, while the MST might offer a simple and accessible alternative for initial screening in the future, especially in non-specialized settings, its variability in sensitivity and specificity, along with an actual lack of standardization, necessitates cautious interpretation. Further studies are necessary before recommending the test in clinical routine.

Cross-cultural adaptation of the Thai Xerostomia Inventory and Summated Xerostomia Inventory.

OBJECTIVE: To cross-culturally adapt and validate the Thai version of the Xerostomia Inventory (XI) and Summated Xerostomia Inventory (SXI) for subjective evaluation of oral dryness in Thai middle-aged and older adults. METHODS: The original English versions of the XI and SXI were cross-culturally translated into Thai. Content validity was examined by the expert panel and 30 pilot subjects. The XI/SXI-Thai were then administered to 200 Thai adults (aged 50 years or older) for further assessment of psychometric properties. The standard question, the Bother Index, and the Xerostomia Questionnaire were used as comparator instruments for the evaluation of criterion and construct validity, respectively. Internal consistency reliability was assessed using Cronbach's alpha. RESULTS: The final XI/SXI-Thai were found to have good content validity. Both scales were able to distinguish between xerostomia and non-xerostomia groups. We observed moderate to strong correlation between the XI/SXI-Thai and other comparator instruments, reflecting good criterion and construct validity. Cronbach's alpha values were 0.875 and 0.847 for the XI-Thai and SXI-Thai, respectively. CONCLUSIONS: The XI-Thai and SXI-Thai were found to be valid, reliable, and easily administrable instruments for xerostomia assessment in Thai middle-aged and older individuals in both clinical and research settings.

A real-life experience of long-term use of pilocarpine in irradiated head and neck cancer patients.

AIMS: To assess long-term efficacy and side effects of pilocarpine on irradiated head and neck cancer (HNC) patients in both for prevention and treatment of radiation-induced xerostomia (RIX). METHODS: Retrospective observational study was conducted. Eligibility criteria included irradiated HNC patients who received pilocarpine at least 12 weeks either for prevention (group A) or for treatment (group B) of RIX. We collected the documented Late Effect Normal Tissue Task Force-Subjective, Objective, Management, Analytics subjective/objective grades of RIX before (only group B) and the latest visit for pilocarpine prescription, dosage, side effects, duration of treatment, and the cause of discontinuation. RESULTS: Between December 2007 and June 2022, 182 patients were enrolled including 95 patients (52%) in group A and 87 patients (48%) in group B. Group A patients reported grades 1, 2, 3, and 4 objective RIX in 0%, 7%, 93%, and 0%. Grade 1, 2, and 3 subjective RIX were 57%, 28%, and 15%. All patients in group B had grade 3 both objective/subjective RIX. The overall improvement of objective/subjective RIX was found in 40%/83%. Discontinuation was found in 51% of patients due to tolerable symptoms or deterioration of the patient's status. CONCLUSIONS: Based on this retrospective analysis, long-term use of pilocarpine in irradiated HNC appears feasible for both prevention and treatment of RIX.

The minimally important difference for the Xerostomia Inventory among Sjögren's disease patients.

OBJECTIVE: Until now, the clinically relevant improvement for the Xerostomia Inventory (XI) has not been defined. Therefore, our aim was to determine the Minimally Important Difference (MID) of the XI for improvement in dry-mouth symptoms in SjD patients. METHOD: The study recruited 34 SjD patients who underwent sialendoscopy of major salivary glands and 15 SjD patients in a nonintervention control group. XI scores were assessed at several time points. The MID was determined from the mean difference in XI scores between the groups with and without improvement. RESULTS: In the control group, no significant XI score changes were seen. In the sialendoscopy group, a clinically relevant XI score change of four scale points was identified after 1 week. For a prolonged duration (≥16 weeks), a minimum reduction of seven scale points in the XI score was required to indicate clinically relevant improvement. CONCLUSION: In SjD patients, a minimum change of four points in the XI score indicates a clinically relevant improvement for evaluating short-term effects. For prolonged effects, a clinically relevant improvement requires a MID of seven points. The determination of the MID in XI could assist in future studies that evaluate changes in xerostomia.

Oral conditions are associated with salt taste disability among American adults.

AIM: To explore the association between oral conditions and their interaction with salt taste disability among American adults. METHODS: Data from the 2013-2014 NHANES cycle were used (n = 2373). The exposures were periodontitis, defined by the 2017 EFP-AAP classification, dental caries, missing teeth, and edentulism, as per the DMF-T index, and xerostomia. The outcome was salt taste disability, objectively assessed. Covariates included sex, age, educational level, poverty index, obesity, diabetes, smoking, alcohol consumption, and medications related to mouth dryness. Weighted multivariable logistic regression modeling was used to evaluate the relationship between oral conditions and their interaction and salt taste disability. RESULTS: Participants who reported xerostomia were more likely to have salt taste disability (OR 2.42; 95%CI 1.44-4.07), especially those older than 60 years (OR 3.63; 95%CI 1.72-7.63). Among participants aged 40-59, xerostomia increased the chance of salt taste disability; however, the confidence interval included the null value. The interactions between xerostomia and edentulism increased the chance of salt taste disability. CONCLUSION: Oral conditions seem to influence the ability to taste salt. Dental professionals may help identify individuals with taste alterations and raise their awareness of the risk of systemic diseases that require the reduction of salt intake.

Dysphagia and Dysphonia After Head and Neck Cancer.

OBJECTIVE: The purpose of this work is to synthesize the latest developments in diagnosis and management of acute and late dysphagia and dysphonia in oral cavity cancer. METHODS: A literature search was conducted using PubMed, Web of Science, Embase and Google Scholar in May 2024 of articles published between 2021 and 2024. Keywords in the search terms included oral cavity cancer, dysphagia, dysphonia, deglutition, swallowing, voice, oral cavity cancer treatment, oral cavity radiation, chemotherapy, dysgeusia, xerostomia, swallow preservation. RESULTS: Twenty-seven pertinent studies fit the inclusion criteria. The most common dysphagic complaints following head and neck cancer are trismus, xerostomia, mucositis and dysphagia. Dysphonia, change in voice is reported by half of head and neck cancer survivors. Fibrosis and neuropathy following radiation therapy to the oral cavity, tongue, oropharynx and its surrounding structures is the most common etiology of post-treatment dysphonia. CONCLUSIONS: Oral cavity cancers cause speech and swallowing dysfunction due to both anatomic and post-treatment changes. These sequalae can be detrimental to the quality of life of the head and neck cancer survivor. For both dysphagia and dysphonia after head and neck cancer early speech and swallow therapy with a Speech Language Pathologist are essential to restoring and maintaining function.

Females have lower salivary flow than males, before and after radiation therapy for head/neck cancer.

OBJECTIVE: To compare salivary flow rates between females and males, before and after radiation therapy (RT) for head and neck cancer (HNC). METHODS: Prospective observational multicenter cohort study (OraRad). Stimulated whole salivary flow was measured before RT and at 6 and 18 months after RT. RESULTS: Mean (95% confidence interval) salivary flow in g/min before RT was 0.81 (0.71, 0.90) in females (n = 107) and 1.20 (1.15, 1.25) in males (n = 391) (p < 0.001); at 6 months was 0.34 (0.24, 0.44) in females and 0.50 (0.44, 0.55) in males (p = 0.01); at 18 months was 0.49 (0.38, 0.59) in females and 0.70 (0.64, 0.75) in males (p < 0.001). Median nadir salivary flow after RT was 0.22 in females and 0.35 in males (p < 0.001). A lower nadir salivary flow in females, but not males, was associated with an increased risk for tooth failure (p = 0.02). CONCLUSIONS: Females with HNC have lower stimulated whole salivary flow than males, before and after RT. Low salivary flow after RT may be a risk factor for tooth failure among females. The lower pre-RT salivary flow rates in females, combined with prior literature in other populations, indicates that, in general, females have lower stimulated salivary flow than males.