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The aim of this study was to describe gender-related differences in characteristics and mortality in heart failure (HF) patients managed in primary care (PC). We included 1802 hF patients aged 77.5 ± 8.8 years (47% women) with ejection fraction (EF) ≥ 40% from the Swedish Heart Failure (SwedeHF) registry. The patients were divided by gender, and by heart failure with mildly reduced ejection fraction (HFmrEF; EF 40–49%) or heart failure with preserved ejection fraction (HFpEF; EF ≥ 50%). Men included in the study were younger (mean-age 76.4 vs 78.7 years, p

Background and purpose: Distinguishing branchial cleft cysts (BrCCs) from cystic metastases of human papillomavirus (HPV) positive tonsillar or base of tongue squamous cell carcinoma and cancer of unknown primary (CUP) is challenging. Fine needle aspiration cytology (FNAC) from cystic metastasis can be nonrepresentative, while reactive squamous cells from BrCC can be atypical. It is unclear whether benign characteristics and the absence of HPV-DNA in FNAC can enhance distinguishing BrCC from a cystic metastasis; therefore, we investigated here. Patients/materials and methods: Morphology and HPV-DNA in FNAC were reevaluated preoperatively and correlated to final diagnosis of 304 BrCC and CUP patients at Karolinska University Hospital during 2016-2023. Results and interpretation: All 176 cases finally diagnosed as BrCC were HPV-DNA negative in the preoperative FNAC. HPV-DNA was present in 100/128 (78.1%) of the FNAC with a solitary cystic neck metastasis and in 3/3 CUPs separately investigated on surgical specimens, which is distributed in 40/58 (69.0%) CUP, 40/41 (97.6%) tonsillar cancer, 21/22 (95.5%) base of tongue cancer, 2/2 uterine cervical cancer, and 0/5 non-HPV-related cancers. Interpretation: All cases with final BrCC diagnosis were HPV-DNA negative in FNAC. HPV-DNA was only present in FNAC of malignant cystic neck masses of HPV-related tumors or CUP. The data suggest that HPV-DNA analysis in FNAC enhances the diagnostics of cystic masses of the neck. A FNAC with a benign morphology and the absence of HPV-DNA indicated a BrCC, while an HPV-DNA positive aspirate irrespective of morphology suggested an HPV-DNA positive cancer or CUP.

Study design: Case report. Objective: To present two cases of young children with Hyaline Fibromatosis Syndrome and their oral and maxillofacial manifestations. Methods: The different oral and maxillofacial manifestations were clinically examined in detail. The patients were treated with surgical excisions of their gingival hyperplasias and soft tissue tumors of the head. Results: Relief of pain from ears, scalp and intraoral was obtained, resulting in a normal eating and nutritional habits despite absence of teeth. Improved esthetics. Conclusion: This paper underscores the importance of early diagnosis and prompt therapeutic interventions in managing Hyaline Fibromatosis Syndrome. This report contributes to the growing body of knowledge regarding this rare disorder and emphasizes the importance of a multidisciplinary approach in achieving favorable outcomes for patients afflicted with HFS.

Abstract Background Empagliflozin reduces the risk of cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM) and high cardiovascular risk via mechanisms which have not been fully explained. The mechanisms of such benefit have not been fully understood, and whether empagliflozin can be safely administered as first-line treatment in patients with CVD at the initial stages of glycaemic perturbations remains to be established. We investigated the effects of empagliflozin on insulin resistance, insulin sensitivity and β-cell function indexes in patients with a recent acute coronary event and newly detected dysglycaemia, i.e., impaired glucose tolerance (IGT) or T2DM. Methods Forty-two patients (mean age 67.5 years, 19% females) with a recent myocardial infarction (n = 36) or unstable angina (n = 6) and newly detected dysglycaemia were randomized to either empagliflozin 25 mg daily (n = 20) or placebo (n = 22). Patients were investigated with stress-perfusion cardiac magnetic resonance imaging before randomization, 7 months after the start of study drug and 3 months following its cessation. Indexes of insulin resistance, sensitivity and β-cell function were calculated based on glucose and insulin values from 2-hour oral glucose tolerance tests (OGTT) and fasting C-peptide. The differences in glucose, insulin, C-peptide, mannose levels and indexes between the two groups were computed by repeated measures ANOVA including an interaction term between the treatment allocation and the time of visit. Results After 7 months, empagliflozin significantly decreased glucose and insulin values during the OGTT, whereas C-peptide, mannose and HbA1c did not differ. Empagliflozin significantly improved insulin sensitivity indexes but did not impact insulin resistance and β-cell function. After cessation of the drug, all indexes returned to initial levels. Insulin sensitivity indexes were inversely correlated with left ventricular mass at baseline. Conclusions Empagliflozin improved insulin sensitivity indexes in patients with a recent coronary event and drug naïve dysglycaemia. These findings support the safe use of empagliflozin as first-line glucose-lowering treatment in patients at very high cardiovascular risk with newly diagnosed dysglycaemia. Trial registration number EudraCT number 2015-004571-73.

Abstract Background Sentinel lymph node biopsy (SLNB) is used to improve the staging of and guide treatment in patients with early‐stage T1–T2 N0 oral squamous cell carcinoma (OSCC). The role of sentinel nodes (SNs) and the use of SN‐technique in advanced OSCC (T3–T4 and/or N+) remain to be evaluated. This study investigates the nodal drainage and the rate of positive SNs (SNs+) in all stages of OSCC. Materials and Methods In total, 85 patients with T1–T4 OSCC diagnosed 2019–2021 were included. We used a prolonged interval between peritumoral injection of radionuclide and SPECT–CT to include all SNs. Results Patients with advanced OSCC presented a higher proportion of contralateral lymphatic drainage and a higher rate of SN+ compared to patients with early‐stage disease. T3–T4 and N+ tumors presented a tendency for a higher rate of contralateral lymphatic drainage compared to T1–T2 and N0 tumors (p = 0.1). The prevalence of positive nodes (SNs+) was higher among patients with advanced disease, T3–T4 versus T1–T2 (p = 0.0398). Conclusion SN‐assisted ND enables identification and removal of all SNs + and has the potential for more accurate staging and could possibly give prognostic advantages regarding regional recurrence for all OSCC patients, especially among those with advanced disease. The precise localization of the SNs + also suggests that a more individualized ND approach might be possible in the future even for patients with advanced OSCC.

BackgroundSymptomatic irreversible pulpitis (SIP) or symptomatic apical periodontitis (SAP) are two painful conditions often warranting emergency treatment. The most common emergency treatments supported by evidence are pulpotomy and pulpectomy and are normally performed under time-constrained circumstances. However, there is no strong evidence of which treatment suggested in literature a clinician can use to reduce endodontic pain effectively. Therefore, the aim of this systematic review is to investigate the present knowledge on postoperative pain related to the two types of emergency treatments available for treating SIP and SAP.MethodsRandomized controlled trials investigating postoperative pain after emergency treatments (pulpotomy and/or pulpectomy) on permanent dentition with signs and symptoms of SIP and/or SAP were searched in three major databases from 1978 until 2022. Risk of bias was assessed with Cochrane's tool.ResultsOnly five studies fulfilled the inclusion criteria. The included studies indicated that pulpotomy and pulpectomy are both suitable treatment options for SAP and SIP, as they provide sufficient alleviation of pain in permanent dentition. However, inconsistent results were found between the included trials on which emergency treatment is more effective in reducing pain. Cochrane's tool revealed that the studies had a low risk of bias. Limitations found in the design of the included randomized control trials decreased the level of evidence. None of the included studies accounted for essential confounding variables, such as factors affecting pain (including the psychological aspects). Moreover, possible non-odontogenic pain was not assessed, and therefore, it was not excluded; hence, affecting the internal validity of the studies.ConclusionThere are controversies within the available randomized control trials on which treatment is most effective in reducing emergency pain. This could be due to some weaknesses in the design of the clinical trials. Thus, further well-designed studies are warranted to draw conclusions on which emergency treatment is more effective in reducing pain.Systematic Review RegistrationPROSPERO (CRD42023422282).

Poverty in childhood is associated with an increased risk of being marginalised and socially excluded, which is also the case in the Swedish welfare state. Poor parents often strive for their children to fit in among same‐aged children, which is difficult for the poorest to accomplish. As the last resort for the poor, the welfare state offers the opportunity to apply for financial aid, but applications may be rejected. Parents can then appeal the rejections to an administrative court. In these decisions, the UN Convention on the Rights of the Child could be applied or referred to. The convention has been incorporated into Swedish law since 2020. This article is grounded in childhood sociology and aims to show how poor children, their needs, and rights are processed in the legal system, which sets the framework for the children’s access to material conditions needed for inclusion in a welfare state such as Sweden. The presentation is based on a qualitative content analysis of administrative court records concerning financial aid appeals. The results show that the appeal process confirms the adult orientation of financial aid and that a child rights perspective is, with few exceptions, missing in these records. When children are mentioned, a care perspective dominates and their right to participation is neglected.

Abstract Background Plasma mannose, an emerging novel biomarker of insulin resistance, is associated with both diabetes mellitus and coronary atherosclerosis, but the relationship between mannose concentrations and myocardial infarction (MI) across different glycaemic states remains to be elucidated. The aim of this study was to investigate the independent association between mannose and a first MI in a group of subjects characterized according to their glycaemic state. Methods Fasting plasma mannose concentrations were analysed in 777 patients 6–10 weeks after a first myocardial infarction and in 770 matched controls by means of high-performance liquid chromatography coupled to tandem mass spectrometry. Participants without known diabetes mellitus were categorized by an oral glucose tolerance test (OGTT) as having normal glucose tolerance (NGT, n = 1045), impaired glucose tolerance (IGT, n = 246) or newly detected type 2 diabetes (T2DM, n = 112). The association between mannose and MI was investigated across these glycaemic states by logistic regression. Results Mannose levels increased across the glycaemic states (p

Abstract Background Mannose binding lectin (MBL) has been suggested to be associated with an impaired cardiovascular prognosis in dysglycaemic conditions, but results are still contrasting. Our aims are (i) to examine whether MBL levels differ between patients with an acute myocardial infarction (MI) and healthy controls and between subgroups with different glucose tolerance status, and (ii) to investigate the relation between MBL and future cardiovascular events. Methods MBL levels were assessed at discharge and after 3 months in 161 AMI patients without any previously known glucose perturbations and in 183 age- and gender-matched controls from the Glucose metabolism in patients with Acute Myocardial Infarction (GAMI) study. Participants were classified as having dysglycaemia, i.e. type 2 diabetes or impaired glucose tolerance, or not by an oral glucose tolerance test. The primary outcome was a composite of cardiovascular events comprising cardiovascular death, AMI, stroke or severe heart failure during 11 years of follow-up. Total and cardiovascular mortality served as secondary outcomes. Results At hospital discharge patients had higher MBL levels (median 1246 μg/L) than three months later (median 575 μg/L; p

Background and Aim: The study 'Periodontitis and Its Relation to Coronary Artery Disease' (PAROKRANK) reported an association between periodontitis (PD) and the first myocardial infarction (MI). This follow‐up study aims to test the hypothesis that those with PD—compared to periodontally healthy individuals—are at increased risk for cardiovascular (CV) events and death. Methods: A total of 1587 participants (age <75 years; females 19%) had a dental examination including panoramic radiographs between 2010 and 2014. PD was categorized as healthy (≥80% alveolar bone height), mild/moderate (79%–66%) or severe (<66%). A composite CV event (first of all‐cause death, non‐fatal MI or stroke and hospitalization following to heart failure) was investigated during a mean follow‐up period of 9.9 years (range 0.2–12.5 years). Participants were divided into two groups: those with and without PD. The primary event rate, stratified by periodontal status at baseline, was calculated using the Kaplan–Meier method and Cox regression. Results: The number of events was 187 in the 985 periodontally healthy participants (19%) and 174 in the 602 participants with PD (29%; p < 0.0001). Those with PD had a higher likelihood for a future event (hazard ratio [HR] = 1.26; 95% CI: 1.01–1.57; p = 0.038), following adjustment for age, smoking and diabetes. Conclusion: The PAROKRANK follow‐up revealed that CV events were more common among participants with PD, which supports the assumption that there might be a direct relation between PD and CV disease. [ABSTRACT FROM AUTHOR]

Ameloblastoma is a rare epithelial odontogenic tumor of the oral cavity, representing only 1% of all oral tumors. Despite being a benign neoplasm, ameloblastomas are slow-growing, locally aggressive tumors that may infiltrate adjacent tissues, causing extensive tissue destruction. It usually presents as an asymptomatic swelling in the posterior region of the mandible. Ameloblastoma in non-tooth-bearing areas is very rare.We present a case of peripheral ameloblastoma (PA) appearing as a solid mass in the temporal fossa. The lesion was initially diagnosed as a cystic lesion and hematoma, but further treatment with complete removal and histopathological analysis led to the diagnosis of PA.

ABSTRACT Escherichia coli arbitrarily encompasses facultative anaerobic, rod-shaped bacteria with defined respiratory and fermentative types of metabolism. The species diversification has been further advanced by atypical strains whose features deviate from the essential species-specific morphological and metabolic cutoff. The morphological cutoff is exemplified by bacterial filamentation. E. coli filamentation has been studied from two different perspectives: the first considers filamentation as a result of adaptive strategies and response to stress, while the second is based on findings from the cell division of E. coli’s conditional mutants. Another cutoff is represented by E. coli’s inability to use citrate as a sole carbon and energy source. In this study, we compared two atypical E. coli strains that belong to the same neuroinvasive ecovar but exhibit either of the two phenotypes that deviate from the species’ features. While E. coli RS218 exists in the form of filaments incapable of growth on citrate, strain IHE3034 is represented as normal-sized bacteria able to ferment citrate under oxic conditions in the presence of glucose; in this paper, we show that these two phenotypes result from a bona fide trade-off. With the help of comparative proteomics and metabolomics, we discovered the proteome required for the upkeep of these phenotypes. The metabolic profiles of both strains reveal that under aerobic conditions, RS218 undergoes oxidative metabolism, while IHE3034 undergoes anaerobic respiration. Finally, we show that the use of citrate and filament formation are both linked in a trade-off occurring via a c-di-GMP-dependent phase variation event. IMPORTANCE Aerobic use of citrate and filamentous growth are arbitrary cutoffs for the Escherichia coli species. The strains that exhibit them as stable phenotypes are called atypical. In this study, we compare two atypical neuroinvasive E. coli strains, which alternatively display either of these phenotypes. We present the proteome and metabolome required for the maintenance of filamentous growth and show that anaerobic nitrate respiration is the main requirement for the use of citrate. The fact that the two phenotypes are differentially expressed by each strain prompted us to check if they are part of a trade-off. Indeed, these atypical characters are reversible and result from a c-di-GMP phase variation event. Thus, we revealed hidden links between stable morphological and metabolic phenotypes and provided information about alternative evolutionary pathways for the survival of E. coli strains in various host niches.

Employees of Small and Medium-sized Enterprises (SMEs) can benefit from occupational health services (OHS) in the same way that employees of large organizations do. The aim of this 3-year trial was to investigate whether integrating multiple SMEs into virtual joint companies may result in incentive structures like those of large companies concerning access to Occupational Health Services (OHS), which can improve wellbeing and reduce the number of sickness visits to clinics. Several SMEs were grouped together to form virtual organizations to enter into agreements with OHS providers. Two groups were created, each with a somewhat different price structure: one with a fixed annual fee and the other with a cost-dependent fee. The number of sickness visits to clinics increased among those who worked under the cost-dependent fee system, whereas it decreased among those who worked under the fixed-fee system. The findings on the work climate were inconclusive because there was no discernible difference. The improved productive time was particularly appealing to SME businesses, since employees could rapidly schedule sickness visit and they were able to spend less time dealing with sickness-related paperwork. It also raised their awareness of their employees' health. When OHS providers could address SMEs as a group, their desire to collaborate with them improved. Furthermore, the local entrepreneur organizations, which served as the virtual headquarters for the SME groups, stated that they would be willing to continue with the work for a rather moderate compensation. The ability of SMEs to create legal organizations in the form of virtual joint companies appears to address, at least partially, the issues related with the conflict between their small sizes and Occupational Safety and Health (OSH) incentive systems to address work accidents and disease incidences. Using the proposed approach would allow for differential fee systems, as well as economic incentive systems, which presently apply predominantly to large firms, might be extended to SMEs.

Abstract Hypopharyngeal squamous cell carcinoma (HPSCC) has a very poor prognosis. Local surgery may increase survival, but is often avoided due to significant post-op co-morbidities. Since prognostic markers are lacking, the aim was to find predictive biomarkers that identify patients whose response to oncological treatment is poor and who may benefit from primary surgery to increase survival. Pretreatment biopsies from 23 HPSCC patients, 3 human papillomavirus (HPV) positive and 20 HPV-negative, were analyzed for expression of 750 mRNAs using the Nanostring nCounter IO360 panel in relation to 3-year survival. Validation was performed through immunohistochemistry (IHC) for HLA class I and S100A12 in 74 HPV-negative HPSCC samples. Clustering identified a subset of HPV-negative HPSCC with favorable prognosis and a gene expression signature overexpressing calgranulins and immune genes, distinct from that of HPV-positive HPSCC. Enrichment analysis showed immune signaling, including the tumor inflammation signature, to be enriched in surviving patients. IHC validation confirmed high S100A12 and HLA class I expression to correlate with survival in HPV-negative HPSCC. This shows that immune activity is strongly related to survival in HPV-negative HPSCC. Enrichment of the tumor inflammation signature indicates a potential benefit of immunotherapy. Low expression of both HLA class I and S100A12 could be used to select patients for local surgery.

Members of the human papillomavirus (HPV) family have been known for causing cancers and condylomas in the anogenital tract for some time, as reflected by the Nobel Prize in Medicine given to Professor Harald zur Hausen 2008 [...]

Abstract Studies have suggested that fluoxetine might improve neurological recovery after stroke, but the results remain inconclusive. The EFFECTS (Efficacy oF Fluoxetine – a randomisEd Controlled Trial in Stroke) reached its recruitment target of 1500 patients in June 2019. The purpose of this article is to present all amendments to the protocol and describe how we formed the EFFECTS trial collaboration in Sweden. Methods In this investigator-led, multicentre, parallel-group, randomised, placebo-controlled trial, we enrolled non-depressed stroke patients aged 18 years or older between 2 and 15 days after stroke onset. The patients had a clinical diagnosis of stroke (ischaemic or intracerebral haemorrhage) with persisting focal neurological deficits. Patients were randomised to fluoxetine 20 mg or matching placebo capsules once daily for 6 months. Results Seven amendments were made and included clarification of drug interaction between fluoxetine and metoprolol and the use of metoprolol for severe heart failure as an exclusion criterion, inclusion of data from central Swedish registries and the Swedish Stroke Register, changes in informed consent from patients, and clarification of design of some sub-studies. EFFECTS recruited 1500 patients at 35 centres in Sweden between 20 October 2014 and 28 June 2019. We plan to unblind the data in January 2020 and report the primary outcome in May 2020. Conclusion EFFECTS will provide data on the safety and efficacy of 6 months of treatment with fluoxetine after stroke in a Swedish health system setting. The data from EFFECTS will also contribute to an individual patient data meta-analysis. Trial registration EudraCT 2011-006130-16. Registered on 8 August 2014. ISRCTN, ISRCTN13020412. Registered on 19 December 2014. ClinicalTrials.gov: NCT02683213. Retrospectively registered on 2 February 2016.

Aim: The prognostic value of natriuretic peptides in the management of heart failure (HF) patients with ejection fraction (EF) 40%, HFpEF) managed in primary care. We show that high NT-proBNP predicts increased all-cause mortality in HFpEF-patients managed in primary care. The clinical use is however limited due to large standard deviations, many co-morbidities and high age. Many of these co-morbidities contribute to all-cause mortality and management of these patients should also focus on these co-morbidities.

Abstract Background Human papillomavirus (HPV) is a causative agent for tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC), as well as for cervical cancer. Premalignant stages in cervical cancer have been studied extensively, while little is known about premalignant stages in TSCC/BOTSCC and the role of HPV. Here we analyzed differences in gene and protein expression between high‐grade dysplasia and invasive cancer in both HPV‐positive (HPV+) and HPV‐negative (HPV−) TSCC/BOTSCC. Methods High‐grade dysplasia and invasive carcinoma were laser microdissected from HPV+ and HPV− TSCC/BOTSCC tumor sections. Differential gene expression was studied utilizing nanoString RNA‐panels and genes of interest were validated on the protein level by immunohistochemistry. Results Forty genes in the HPV+ tumors showed significantly different expression between high‐grade dysplasia and invasive cancer and 33 genes in the HPV− tumors. Five out of the nine most significant pathways showed similar increased activity in invasive cancer as compared to high‐grade dysplasia in both HPV+ and HPV− tumors. Lastly, significant differences in protein expression was confirmed for SPARC, psoriasin, type I collagen and galectin‐1 in both HPV+ and HPV− tumors. Conclusions This is to our knowledge the first study disclosing differences and similarities in gene expression between dysplastic and invasive HPV+ and HPV− TSCC/BOTSCC.

Abstract Background Many randomised controlled trials (RCT) fail to meet their recruitment goals. Study personnel play a key role in recruitment. The aim of this study was to identify successful strategies that study personnel consider to be important in patient recruitment to RCT. Methods We constructed a questionnaire based on the literature, discussions with colleagues and our own experience as trialists. The survey was named “What is Important for Making a Study Successful questionnaire” (WIMSS-q). Our target group was the study personnel in the ongoing EFFECTS study. The questionnaire was sent out electronically to all physicians and nurses (n = 148). Success factors and barriers were divided according to patient, centre and study level, respectively. Results Responses were received from 94% of the study personnel (139/148). The five most important factors at centre level for enhancing recruitment were that the research question was important (97%), a simple procedure for providing information and gaining consent (92%), a highly engaged local principal investigator and research nurse (both 87%), and that study-related follow-ups are practically feasible and possible to coordinate with the clinical follow-up (87%). The most significant barrier at the local centre was lack of time and resources devoted to research (72%). Important patient-related barriers were fear of side effects (35%) and language problems (30%). Conclusions For recruitment in an RCT to be successful, the research question must be relevant, and the protocol must be simple and easy to implement in the daily routine. Trial registration The protocol for this study was registered at the Northern Ireland Hub for trials methodology research (SWAT ID 64). The EFFECTS study has EudraCT number 2011–006130-16 and was registered 17 February 2016 at ClinicalTrials.gov number NCT02683213.

Within caring science, the concept of caring leadership is well established. The aim of this study is to introduce Bondas's theory of caritative leadership into education. The theory of caritative leadership is a theory of caring leadership with the 'caritas' thought of human love and mercy at its core. The article considers a hypothetical testing of the transferability of a nursing leadership theory, with its roots in caring science, into the field of education. The material consists of about 90 sources from the disciplines of nursing, education, management, and psychology. A caritative leadership would support Bildung--a comprehensive view of the edification of life, personal growth and maturity--as an ultimate goal of education. In the emerging model of a caritative leadership in education, a humanistic ethos of love, trust, and forgiveness shapes the culture of the educational organisation. The pedagogical leader supports the process of human becoming by implementing the idea of human beings as vulnerable, moral, dignified and unique individuals. The leader develops an ability to know which objectives to measure and which experiences of others to learn from, while performing such tasks as planning, reporting and directing in accordance with the mission of the organisation.

The oral cavity is the habitat of several hundreds of microbial taxa that have evolved to coexist in multispecies communities in this unique ecosystem. By contrast, the internal tissue of the tooth, i.e., the dental pulp, is a physiologically sterile connective tissue in which any microbial invasion is a pathological sign. It results in inflammation of the pulp tissue and eventually to pulp death and spread of inflammation/infection to the periradicular tissues. Over the past few decades, substantial emphasis has been placed on understanding the pathobiology of root canal infections, including the microbial composition, biofilm biology and host responses to infections. To develop clinically effective treatment regimens as well as preventive therapies, such extensive understanding is necessary. Rather surprisingly, despite the definitive realization that root canal infections are biofilm mediated, clinical strategies have been focused more on preparing canals to radiographically impeccable levels, while much is left desired on the debridement of these complex root canal systems. Hence, solely focusing on “canal shaping” largely misses the point of endodontic treatment as the current understanding of the microbial aetiopathogenesis of apical periodontitis calls for the emphasis to be placed on “canal cleaning” and chemo-mechanical disinfection. In this review, we dissect in great detail, the current knowledge on the root canal microbiome, both in terms of its composition and functional characteristics. We also describe the challenges in root canal disinfection and the novel strategies that attempt to address this challenge. Finally, we provide some critical pointers for areas of future research, which will serve as an important area for consideration in Frontiers in Oral Health.

ObjectivesHuman papillomavirus positive (HPV+) tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC), the major subsites of oropharyngeal squamous cell carcinoma (OPSCC) have favorable outcome, but upon relapse, outcome is poor and new therapies needed. Since, phosphatidyl-inositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) and fibroblast-growth-factor-receptor-3 (FGFR3) mutations often occur in such tumors, here, we tested targeted therapy directed to such genes in TSCC/BOTSCC cell lines. We also combined the two types of inhibitors with each other, and cisplatin or docetaxel that are used clinically.MethodsThe HPV+ CU-OP-2, -3, -20, UPCI-SCC-154, and HPV- CU-OP-17 and UT-SCC-60A cell lines were first tested for common PIK3CA/FGFR3 mutations by competitive-allele-specific TaqMan-PCR. They were then treated with the food and drug administration (FDA) approved drugs, alpelisib (BYL719) and erdafitinib (JNJ-42756493) alone and in combination with cisplatin or docetaxel. Viability, proliferation, apoptosis and cytotoxicity responses were thereafter followed by WST-1 assays and the IncuCyte S3 Live® Cell Analysis System.ResultsHPV+ CU-OP-2 had a pS249C-FGFR3, and like CU-OP-20, a pE545K-PIK3CA mutation, while no other lines had such mutations. Irrespectively, dose dependent responses to all PI3K/FGFR inhibitors were obtained, and upon combining the inhibitors, positive effects were observed. Cisplatin and docetaxel also induced dose dependent responses, and upon combination with the inhibitors, both positive and neutral effects were found.ConclusionsThe data suggest that FDA approved drugs alpelisib and erdafitinib efficiently inhibit TSCC/BOTSCC cell line growth, especially when combined irrespective of presence of corresponding mutations and should be further explored, for use upon recurrent disease.