Oropharyngeal Carcinoma Research Articles

Abstract 1025: An AI based CT scan classifier for predicting extranodal extension and nodal metastasis of HPV-associated oropharyngeal carcinoma

Abstract Background: Pathologic extranodal extension (ENE) and nodal metastasis (NM) are of prognostic significance in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). The pretreatment identifications of these two factors through computed tomography (CT) imaging are of clinical importance since they could guide treatment de-escalation protocols and select candidates suitable for surgery. In an effort to enhance pretreatment decision making, we developed and validated an AI model (specifically a multi-layer perceptron (MLP)-based deep learning model) to predict radiologic NM and pathologic ENE in HPV-associated OPSCC patients. Methods: Radiographic CT scans for 290 OPSCC patients treated with definitive chemoradiation were acquired from The Cancer Imaging Archive (TCIA) and divided into training (D1) and validation (D2) cohorts for NM prediction. Radiologic NM for D1 and D2 were reviewed by two radiologists. Only nodes with concordant NM judgments from both radiologists were included for analysis. An additional 46 OPSCC patients treated with surgery at Emory Winship Cancer Institute were collected to form the test cohorts (D3) for ENE prediction. The largest metastatic or normal nodes were annotated for D1 and D2 while all visible nodes with pathology confirmation of ENE from D3 were annotated. We present a novel deep-learning model utilizing U-shaped multi-layer perceptron mixer (MLP-Mixer) to capture both global and local feature representations by spatially aggregating image patch information through a procedure called token-mixing. The model was trained for 20 epochs with learning rate of0.0001 and batch size of 64. The diagnostic performance of the AI model was evaluated on D2 and D3 using accuracy and area under the ROC curve (AUROC). Results: There were 121 NM negative and 130 NM positive nodes in D1, 14 NM negative and 25 NM positive nodes in D2 and 46 ENE negative and 20 ENE positive nodes in D3. On D2 for NM prediction, the AI model achieved overall accuracy of 0.77 and AUROC of 0.78. On D3 for ENE prediction, the AI model achieved overall accuracy of 0.71, AUROC of 0.69, positive predictive value of 0.52 and negative predictive value of 0.86. Conclusions: The new AI–based deep learning model was able to identify HPV-associated OPSCC NM and ENE with satisfactory diagnostic performance and shows promise to assist clinicians in treatment decision-making. Additional, multi-site prospective validation of the approach is warranted. Citation Format: Bolin Song, Kailin Yang, Shaoyan Pan, Liping Li, Qiyun Liu, Jonathan Lee, Sarah Stock, Nabil F. Saba, Mehmet Asim Bilen, Mihir R. Patel, Anant Madabhushi. An AI based CT scan classifier for predicting extranodal extension and nodal metastasis of HPV-associated oropharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1025.

Abstract 1181: Therapeutic efficacy by Streptococcus salivarius as a probiotic in a preclinical model of oropharyngeal carcinoma

Abstract Streptococcus salivarius is a gram-positive, non-pathogenic bacteria found in the oral cavity and upper respiratory tract. This bacterium has been shown to possess antimicrobial properties with the potential to cause activation of natural killer (NK) cells and induction of anti-tumorigenic cytokines such as interferon-gamma and interleukin-12 (IL-12). There is a high abundance of this bacteria in the saliva in oral squamous cell carcinoma patients. Moreover, Streptococcus-reactive cytotoxic T cells were associated with recurrence-free survival. Nevertheless, there is a considerable lack of information regarding the impact of S. salivarius on intratumoral immune responses and its potential as a cancer therapeutic. This study aimed to characterize the immune responses in the tumor microenvironment by S. salivarius in combination with programmed cell death protein 1 (anti-PD-1) therapy and its therapeutic efficacy. We expect that S. salivarius will cooperate with immune checkpoint inhibitors, activating antitumor immune responses. For this project, we used a preclinical murine model where an HPV+ oropharyngeal cancer cell line named mEER was implanted subcutaneously or in the tongue of the mice. We treated with or without S. salivarius and/or anti-PD-1. First, S. salivarius was administered intratumorally on subcutaneous tumors and treated or not with anti-PD-1 therapy administered intraperitoneally. We measured tumor volume and quantified different immune cells by flow cytometry. While anti-PD-1 treated mice showed a continuous increase in tumor volume, the ones treated with anti-PD-1 and S. salivarius reduced the growth rate starting at day 20. Mice treated with anti-PD1 and S. salivarius showed increased CD4+ T cells and myeloid-derived suppressor cells (MDSCs) compared to anti-PD-1 treatment alone. Secondly, we implanted the mice with tongue tumors and applied S. salivarius topically in the oral cavity with or without anti-PD-1. The use of S. salivarius contributed to an increase in CD4+T cells and activation of CD8+T cells and NK cells. The combination of anti-PD-1 with S. salivarius did not further enhance the activation of these cells. Nevertheless, 80% of mice receiving anti-PD-1 with S. salivarius responded to the therapy, whereas 63% responded while receiving only anti-PD-1. In conclusion, Streptococcus salivarius as a probiotic, affected tumor development and immune cell infiltration in oropharyngeal cancer. Future analyses will allow us to explore the effect of the probiotic on the tumor microenvironment and improve colonization in the oral cavity. Citation Format: Jennifer Diaz, Michael Rivera, Kamila A. Del Valle, Edna E. Piñero, Filipa Vitorino, Jorge R. Ortiz, Stephanie M. Estremera. Therapeutic efficacy by Streptococcus salivarius as a probiotic in a preclinical model of oropharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1181.

Early Disease Recurrence Following Post-operative HPV ctDNA Directed Active Surveillance in Oropharyngeal Carcinoma – Outcomes of a Prospective Pilot Study

Early Disease Recurrence Following Post-operative HPV ctDNA Directed Active Surveillance in Oropharyngeal Carcinoma – Outcomes of a Prospective Pilot Study

Imaging-based Prognostic Artificial Intelligence Model for Oropharyngeal Carcinoma after Radiation Therapy

Imaging-based Prognostic Artificial Intelligence Model for Oropharyngeal Carcinoma after Radiation Therapy

270 Radiologic diagnosis of Extranodal Extension (ENE) in patients with HPV-positive oropharyngeal cancer: consensus diagnosis and influence on prognosis

Tumor often progresses through the weakest part of any surrounding tissues. The extent of tumor invasion depends on: a. Aggressiveness of the tumor cells (e.g. number and invasive character of stem cells), b. robustness of the surrounding tissues and their composition (e.g. vessels), and c. time to allow the tumor to proliferate. The lymph node (LN) capsule comprises dense connective tissue stroma and collagenous fibers, and is a natural barrier that generally prevents further tumor progression. Permeation of tumor through the nodal capsule into surrounding tissues is termed “extranodal extension”. The idiosyncratic and inconsistent mechanism of ENE is imprecisely understood, but it is thought to be due to either tumor cell proliferation that outpaces the capacity of nodal capsular expansion (“ruptures” the LN capsule), or factors within the tumor or tumor microenvironment that facilitate the “breach” of the capsule. The latter might explain ENE in small LNs, or a “neglected” tumor (lengthy intranodal tumor growth with eventual “rupture” through an expanded nodal capsule). Several biomarkers (e.g. podoplanin) that are often associated with tumor aggressiveness have been reported to have a high expression in ENE+ LN. ENE represents a spectrum of tumor nodal invasion. The early sign of ENE can only be visible under the microscope (pathologic ENE); when ENE progresses further, the radiographic signal changes become apparent, making it visible on imaging (iENE). Most advanced ENE causes emergence of clinical surrogates (e.g. peau d'orange, or a “fixed” nodal mass), rendering it detectable by regular clinical examination (ENEc). iENE has been reported to be one of the strongest anatomic prognostic factors for overall survival (mainly due to increased risk of distant metastasis) in HPV-positive oropharyngeal carcinoma (HPV+ OPC), and is able to identify a subgroup of stage I disease with poor prognosis. Several deintensification trials (NRG-HN002, ORATOR, ORATOR2, E3311) have excluded HPV+ OPC with some form of iENE from trial enrolment. Several authors have proposed that iENE be included in future clinical N classification for HPV+ OPC. However, adoption of iENE in clinical care remains challenging because it is not a well-defined radiologic feature among the radiology community. Various definitions / descriptions of iENE have been used in literature. There is also insufficient awareness of the prognostic importance of this parameter in head and neck oncology community. The international iENE Expert Panel was convened under the HNCIG comprised expert internationally renowned neuroradiologists and clinicians. Several rounds of Delphi process were conducted to consolidate iENE definition. The consensus recommendations on the terminology and diagnostic criteria for iENE were generated. The experts in the consensus process recognized the following as criteria for the diagnosis of iENE: clear evidence of irregular or indistinct nodal margin/border; extension into perinodal fat; extension into adjacent structures, and conglomerate/matted/coalescent nodes. These recommendations have been endorsed by 19 national organisations, representing 34 countries. With increased awareness and consolidated definition as well as training, iENE could become an important baseline factor for risk stratification and staging in HPV+ OPC.

Quality of life of patients treated with robotic surgery in the oral and maxillofacial region: a scoping review of empirical evidence

BackgroundThere is a blooming trend in the application of robotic surgery in oral and maxillofacial care, and different studies had evaluated the quality of life (QoL) outcomes among patients who underwent robotic surgery in the oral and maxillofacial region. However, empirical evidence on the QoL outcomes from these procedures is yet to be mapped. Thus, this study was conducted to evaluate the available scientific evidence and gaps concerning the QoL outcomes of patients treated with robotic surgery in the oral and maxillofacial region.MethodsThis study adopted a scoping review design, and it was conducted and reported based on the Arksey and O’Malley, PRISMA-ScR, and AMSTAR-2 guidelines. SCOPUS, PubMed, CINAHL Complete, and APA PsycINFO were searched to retrieve relevant literature. Using Rayyan software, the retrieved literature were deduplicated, and screened based on the review’s eligibility criteria. Only the eligible articles were included in the review. From the included articles, relevant data were charted, collated, and summarized.ResultsA total of 123 literature were retrieved from the literature search. After deduplication and screening, only 18 heterogeneous original articles were included in the review. A total of 771 transoral robotic surgeries (TORSs) were reported in these articles, and the TORSs were conducted on patients with oropharyngeal carcinomas (OPC), recurrent tonsillitis, and obstructive sleep apnoea (OSA). In total, 20 different QoL instruments were used in these articles to assess patients’ QoL outcomes, and the most used instrument was the MD Anderson Dysphagia Inventory Questionnaire (MDADI). Physical functions related to swallowing, speech and salivary functions were the most assessed QoL aspects. TORS was reported to result in improved QOL in patients with OPC, OSA, and recurrent tonsillitis, most significantly within the first postoperative year. Notably, the site of the lesion, involvement of neck dissections and the characteristics of the adjuvant therapy seemed to affect the QOL outcome in patients with OPC.ConclusionCompared to the conventional treatment modalities, TORS has demonstrated better QoL, mostly in the domains related to oral functions such as swallowing and speech, among patients treated with such. This improvement was most evident within the initial post-operative year.

A Retrospective Analysis from Western Romania Comparing the Treatment and Survivability of p16-Positive versus p16-Negative Oropharyngeal Cancer.

Oropharyngeal cancer is a global health concern due to its multifaceted nature. Recent molecular studies have linked p16 overexpression, associated with the human papillomavirus, to oropharyngeal cancer and its prognostic implications. This retrospective study in Western Romania examined 60 patients, categorizing them based on p16 biomarker status: 28 were p16 positive, and 32 were p16 negative. Statistical tests, including Fisher's exact and chi2, were used for analysis. Patients with p16-positive oropharyngeal cancer exhibited a better prognosis (3-year survival, p = 0.0477; midtreatment, p = 0.0349) and reported lower alcohol (p = 0.0046) and tobacco (p < 0.0001) use. The study highlights the importance of p16 testing in oropharyngeal carcinoma diagnosis. It suggests modifying treatment approaches based on p16 status and underscores the differing prognoses associated with p16-positive and p16-negative cases.

Single cell analysis unveils the commonality and heterogeneity between nasopharyngeal and oropharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) and oropharyngeal carcinoma (OPC) are subtypes of head and neck cancer with different treatment effects due to the heterogeneity of tumor microenvironments. This study was to investigate the distinctive tumor microenvironments of NPC and OPC. Analyzing single-cell data from 10 cases of each subtype, we reveal significant differences in cellular composition, with NPC microenvironment dominated by T/NK and B cells, and OPC characterized by prevalent epithelial cells and fibroblasts. Dynamic transitions of CD8 T cells are observed in both tumor types, involving shifts from naivety to cytotoxicity, proliferation, and eventual exhaustion/exhausted states. Additionally, Tregs exhibit heightened proliferative abilities in later developmental stages, concomitant with exhaustion. These highly proliferative T cells and Tregs manifest elevated glycolysis and lactate metabolism activities. Furthermore, we explore intercellular communication between glycolytic malignant epithelial cells and these proliferative T cells. These findings offer comprehensive insights into the heterogeneity of tumor microenvironments and provide a solid foundation for future therapeutic strategies and targeted interventions.

Feasibility of Achieving Dose Constraints for Dysphagia Aspiration-Related Structures and Its Clinical Significance in Intensity-Modulated Radiotherapy Planning of Head and Neck Cancer.

Introduction Dysphagia is commonly seen in patients with head and neck cancers after undergoing chemoradiotherapy and is often under-reported and also not given clinical importance. The quality of life of the patients can be significantly improved if the required dose constraints to the dysphagia aspiration-related structures (DARS) are achieved. The present study was conducted in order to determine the feasibility of achieving the dose constraints to DARS between the standard intensity-modulated radiotherapy(st-IMRT) arm and the dysphagia-optimized IMRT (do-IMRT) arm. Material and methods Sixty patients with head and neck cancer were recruited and randomized into two groups: In one group called the st-IMRT, constraints were not given to DARS, and in the other group called the do-IMRT, constraints were given to DARS. Treatment was given in the form of chemoradiation with a dose of 70 Gy in 35 fractions by IMRTtechnique, over seven weeks, 2 Gy per fraction along with weekly concurrent Cisplatin (35 mg/m2) in both the groups. Step and shoot IMRT setup was used for planning, and the system used forplanning was Eclipse 13.6 (Varian Medical System, Inc., Palo Alto, CA, US); progressive resolution optimizeralgorithm was used for optimization, and Anisotropic Analytical Algorithmalgorithm was used for dose calculation. Truebeam was used for treatment delivery. DARS dosimetric parameters assessed were Dmean, V30, V50, V60, V70, D50, and D80. Radiation-induced toxicities to the skin, mucosa, larynx, salivary gland, and dysphagiaand hematological toxicities were assessed in between both the groups during and after radiotherapy up to six months based on Common Terminology Criteria for Adverse Effects v5.0. p-values were calculatedusing the unpaired T-test. Results In the cohort of 60 patients with head and neck cancers, 95% were males. Dosimetric parameters of the planning target volume (PTV) were compared but were not found to be significant. In the dosimetry of the organs at risk, a p-value of some structures was found to be significant although the doses received were well within the tolerable limits in both arms. DARS dosimetry V60 and V70 of the inferior constrictor muscle was found to be statistically significant (p=0.01 and 0.008, respectively). V60 and V70 of larynx were also statistically significant (p=0.009 and 0.000, respectively). V70 and D50 of cricopharyngeus were found to be statistically significant (p=0.01 and 0.03, respectively), V30 and V60 for combined pharyngeal constrictor muscles were found to be statistically significant (p=0.02 and 0.01), and lastly, V60 for combined DARS was also significant (p=0.004). Post-treatment 33.3% of patients in the st-IMRT arm required Ryle's tube placement. No grade 4 toxicities were seen in either arm regarding hematological toxicities, acute or chronic radiation-induced toxicities. In site-wise comparison of doses, the p-value was not found to be significant in patients with oropharyngeal and oral cavity carcinomas but was found to be statistically significant in the larynx and hypopharynx subsites. Conclusion The feasibility of achieving dose constraints to the DARS was seen in cases of laryngeal and hypopharyngeal cancers where the constrictor muscles were at a distance from the PTV. Further, the feasibility of achieving dose constraints may be seen in lower-dose prescriptions either in postoperative cases or in low-risk clinical target volumenodal volumes.

The emerging role of sentinel lymph node biopsy in oral cavity and oropharyngeal carcinomas

Management of clinically negative necks (cN0) in oral cavity (OCSCC) and oropharyngeal (OPSCC) squamous cell carcinoma (SCC) has evolved over time. Historically, the clinically negative neck has been managed with elective neck dissection (END) or observation, but more recently sentinel lymph node biopsy (SLNB) has emerged as a technique to detect occult metastases. In this review, we will discuss the role of SLNB in early-stage OCSCC and in the management of OPSCC.

SIRT1 as a potential key regulator for mediating apoptosis in oropharyngeal cancer using cyclophosphamide and all-trans retinoic acid

Although cyclophosphamide (CTX) has been used for recurrent or metastatic head and neck cancers, resistance is usually expected. Thus, we conducted this study to examine the effect of adding all-trans retinoic acid (ATRA) to CTX, to increase efficacy of CTX and reduce the risk of resistance developed. In this study, we investigated the combined effect of ATRA and CTX on the expression of apoptotic and angiogenesis markers in oropharyngeal carcinoma cell line (NO3), and the possible involved mechanisms. ATRA and CTX in combination significantly inhibited the proliferation of NO3 cells. Lower dose of CTX in combination with ATRA exhibited significant cytotoxicity than that of CTX when used alone, implying lower expected toxicity. Results showed that ATRA and CTX modulated oxidative stress; increased NOx and MDA, reduced GSH, and mRNA expression of Cox-2, SIRT1 and AMPK. Apoptosis was induced through elevating mRNA expressions of Bax and PAR-4 and suppressing that of Bcl-xl and Bcl-2, parallel with increased caspases 3 and 9 and decreased VEGF, endothelin-1 and CTGF levels. The primal action of the combined regimen on inflammatory signaling highlights its impact on cell death in NO3 cell line which was mediated by oxidative stress associated with apoptosis and suppression of angiogenesis.

IFIH1-mediated post-transcriptional regulation of PTTG1 promotes proliferation and affects PHA-848125 sensitivity and prognosis in oropharyngeal carcinoma.

The pituitary tumor-transforming gene 1 (PTTG1) is an oncogene involved in chromosomal segregation, DNA repair, apoptosis, and metabolism. PTTG1 can be used for clinical diagnosis and treatment and is a potential target for oropharyngeal carcinoma. The proliferation and viability of Cal27 and FaDu cells were assessed using the CCK-8 assay. Real-time PCR and western blotting, respectively, were used to analyze the mRNA and protein expression levels of PTTG1 and IFIH1. The interaction between PTTG1 mRNA and the translational regulatory protein IFIH1 was analyzed using RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays. PTTG1 protein was significantly overexpressed in oropharyngeal carcinoma, whereas PTTG1 mRNA was not. We hypothesized that a translation regulatory protein plays a post-transcriptional role in PTTG1. The IFIH1 protein specifically bound to the 42-52 nt region of PTTG1 mRNA, promoted the translation of PTTG1, and promoted the proliferation of oropharyngeal cancer cells. Administration of the PTTG1 inhibitor PHA-848125 and silencing of IFIH1 synergistically decreased the expression of PTTG1, inhibited the proliferation of oropharyngeal cancer cells, and indicated a good prognosis. We found that the IFIH1-PTTG1 axis could regulate the PHA-848125 response and functionally mediate inter-individual oropharyngeal cancer susceptibility and prognosis. This study aimed to confirm the upstream regulatory genes of PTTG1 and further investigate the specific interactions in this signaling pathway, which will provide a new approach for the treatment of oropharyngeal carcinoma.

Case of Pulmonary Tumor Embolism due to Oropharyngeal Carcinoma Diagnosed by a Transbronchial Lung Biopsy.

Pulmonary tumor embolisms (PTEs) are primarily caused by adenocarcinoma. However, only a few cases of oropharyngeal carcinoma have been reported. We herein report a 47-year-old man who presented with a fever, cough, and dyspnea 6 months after treatment for stage II oropharyngeal carcinoma. Chest computed tomography revealed centrilobular granular and nodular shadows and subpleural consolidation. A transbronchial lung biopsy revealed a mass of squamous tumor cells forming emboli in the small vessels, resulting in the diagnosis of PTE due to oropharyngeal carcinoma. Therefore, PTE should be considered for patients with a history of hypoxia.

Current Status of Vaccine of Human Papillomavirus-positive Patients with Oropharyngeal Carcinoma

Abstract The oropharynx is amongst the most common sites of cancer in Indian male population. The human papillomavirus (HPV) infection causes approximately 5% of cancers worldwide. HPV-positive patients (12–16 HPV genotypes) with oropharyngeal carcinoma (OPC) of the tonsil and base of the tongue are increasing significantly not only in India but also in the USA and some European countries. The abovementioned facts were the driving force to conduct this present study. The aims of the present were (1) To know the relationship between the HPV vaccination and the incidence of OPC in men and (2) Can pan-gender HPV vaccination reduce the incidence of HPV patients with OPC. The study reviewed the literature using MEDLINE/PubMed and Google Scholar. The English language articles having abstracts were included on 28 March 2024. The study investigated the effect of HPV vaccination on the incidence and prevalence of HPV-positive men with OPC in the last 3 years (January 2021 to December 2023). The current study observed HPV vaccination reducing the oral HPV positivity in men and indicating the decreased risk of developing HPV-positive patients with not only OPC but also other HPV-associated head-and-neck cancers. The study found that the introduction of pan-gender HPV vaccination can reduce the incidences of HPV-positive men with OPC. Therefore, HPV vaccination in pre-teens, early teens and young boys can prevent not only HPV-positive men with OPC but also other cancers of head-and-neck regions.

Treatment De-escalation for Oropharyngeal Carcinoma in the Human Papillomavirus Era

Treatment of human papillomavirus (HPV) oropharyngeal carcinomas requires a multidisciplinary approach as varied paradigms yield equally favorable oncologic outcomes. Adverse effects from the various treatment modalities can significantly affect quality of life differently and therefore have been important study endpoints in de-escalation trials. This presentation summarizes the management of oropharyngeal carcinomas and strategies to de-intensify treatment with a focus on the reduction of radiation dose. It will review the recent literature supporting the use of biomarkers including functional imaging, circulating HPV tumor DNA, and rapid mid-treatment nodal shrinkage to identify patients in which treatment can be safely de-escalated. Evidence suggests that there may be a group of patients that may benefit from de-escalation of treatment while maximally sparing organs at risk important for swallowing, speech, and salivary flow.

Exploring the Anticancer Properties of Sakuranin Flavanone in Human Oropharyngeal Squamous Carcinoma Cells by Studying Its Effects on Caspase-driven Apoptosis, Mitochondrial Membrane Potential (MMP) Loss, Cell Migratory and Invasiveness and m-TOR/PI3K/AKT Signalling Pathway.

Sakuranin is a flavanone which is a class of flavonoids found abundantly in Prunus species. Flavonoids have been long known for their anticancer properties against a range of human cancers. However, there are no previous reports on the anticancer effects of sakuranin flavanone molecule. This study was designed to study the anticancer effects of sakuranin against human oropharyngeal carcinoma cells along with investigating its effects on caspase-mediated apoptosis, mitochondrial membrane potential (MMP) loss, cell migration and invasion and m-TOR/PI3K/AKT signalling pathway. MTT assay was used to study effects on cell viability. The apoptotic studies were carried out through AO/EB staining, annexin V/FITC staining, comet assay and western blotting assay. Transwell chambers assay was used to study effects on cell migration and invasion. Flow cytometry was used to study effects of Sakuranin on mitochondrial membrane potential loss (MMP). Finally, western blotting was used to investigate m-TOR/PI3K/AKT signalling pathway. Results indicated that Sakuranin led to potent cell proliferation inhibition in a dose-dependent manner. Sakuranin also induced apoptotic cell death as indicated by fluorescence microscopy and annexin V/FITC staining assays. The apoptotic induction was mediated via activation of caspase-3, caspase-9, and Bax while as it led to downregulation of Bcl-2. Sakuranin also caused inhibition of cell migration and cell invasion along with causing significant decrease in MMP. Sakuranin also caused inhibition of expressions of proteins related with m-TOR/PI3K/AKT signalling pathway. In conclusion, the current findings clearly indicate anticancer effects of Sakuranin flavanone in human oropharyngeal cancer cells and are mediated via caspase activated apoptosis, inhibition of cell migration and invasion, loss of mitochondrial membrane potential and targeting m-TOR/PI3K/AKT signalling pathway.

Increasing Patients With HPV-positive Oropharyngeal Squamous Cell Carcinoma and its Oncologic Outcomes in the Rural Region in Northern Japan.

Despite the global rise in the incidence of human papillomavirus (HPV)-positive oropharyngeal carcinoma (OPC) in recent years, its prevalence and oncological outcomes in patients living in rural areas of Northern Japan has not been explored and should be investigated. A total of 105 patients with oropharyngeal squamous cell carcinoma who underwent HPV screening and received first-line treatment were included in this study. The annual changes in the number of patients, survival rates, and clinical factors affecting prognosis were examined. The HPV-positive rate in patients with OPC was low, with the lowest rate of 10.0% in 2013 and the highest rate of 46.7% in 2020. The number of HPV-negative cases remained almost unchanged, whereas the overall number of cases increased with the increasing number of HPV-positive cases. Additionally, HPV-positive cases exhibited a fairly good prognosis. The number of OPC cases increased not only in urban areas, but also in rural areas. HPV-positive cases had better outcomes than HPV-negative cases.

The development of a decision aid for patients with operable oropharyngeal carcinoma in the Netherlands – A mixed methods study

ObjectiveThe aim of this project is to create an interactive online patient decision aid (PDA) for oropharyngeal cancer (OPSCC) patients, eligible for transoral (robotic) surgery with an ultimate goal to assist both physicians and patients in making treatment choices. Materials and methodsFollowing the International Patient Decision Aid Standards, a mixed-methods approach was employed. The study involved semi-structured in-depth interviews with patients and physicians, thinking-out-loud sessions, and study-specific questionnaires. Thematic coding and analysis were conducted on verbatim transcriptions of audio-recorded interviews. ResultsThe PDA drafts were evaluated by twenty OPSCC survivors and twenty multidisciplinary specialists. Significant revisions were made after phase 1 to enhance readability and reduce text, whilst incorporating videos and graphics. Following all phases, both patients and specialists rated the PDA as comprehensible, feasible, and a valuable addition to regular counseling. ConclusionThis study showcases the development of a PDA for early stage oropharyngeal cancer patients considering surgery and radiotherapy options. The decision aid emphasizes the disparities in short- and long-term side effects between the two treatments. Patients and physicians found the decision aid to be understandable, user-friendly, and helpful for future patients. The PDA is available on https://beslissamen.nl/.

Radiomic Analysis for Human Papillomavirus Assessment in Oropharyngeal Carcinoma: Lessons and Pitfalls for the Next Future

Background: Oropharyngeal Squamous Cell Carcinoma (OPSCC) is rapidly increasing due to the spread of Human Papillomavirus (HPV) infection. HPV-positive disease has unique characteristics, with better response to treatment and consequent better prognosis. HPV status is routinely assessed via p16 immunohistochemistry or HPV DNA Polymerase Chain Reaction. Radiomics is a quantitative approach to medical imaging which can overcome limitations due to its subjective interpretation and correlation with clinical data. The aim of this narrative review is to evaluate the impact of radiomic features on assessing HPV status in OPSCC patients. Methods: A narrative review was performed by synthesizing literature results from PUBMED. In the search strategy, Medical Subject Headings (MeSH) terms were used. Retrospective mono- or multicentric works assessing the correlation between radiomic features and HPV status prediction in OPSCC were included. Selected papers were in English and included studies on humans. The range of publication date was July 2015–April 2023. Results: Our research returned 23 published papers; the accuracy of radiomic models was evaluated by ROC curves and AUC values. MRI- and CT-based radiomic models proved of comparable efficacy. Also, metabolic imaging showed crucial importance in the determination of HPV status, albeit with lower AUC values. Conclusions: Radiomic features from conventional imaging can play a complementary role in the assessment of HPV status in OPSCC. Both primary tumor- and nodal-related features and multisequencing-based models demonstrated higher accuracy.

Saliva as a potential non-invasive liquid biopsy for early and easy diagnosis/prognosis of head and neck cancer

Head and neck squamous cell carcinomas (HNSCCs) are the most devastating diseases in India and southeast Asia. It is a preventable and curable disease if detected early. Tobacco and alcohol consumption are the two major risk-factors but infection of high-risk HPVs are also associated with development of predominantly oral and oropharyngeal carcinomas. Interestingly, unlike cervical cancer, HPV-induced HNSCCs show good prognosis and better survival in contrast, majority of tobacco-associated HPV−ve HNSCCs are highly aggressive with poor clinical outcome. Biomarker analysis in circulatory body-fluids for early cancer diagnosis, prognosis and treatment monitoring are becoming important in clinical practice. Early diagnosis using non-invasive saliva for oral or other diseases plays an important role in successful treatment and better prognosis. Saliva mirrors the body's state of health as it comes into direct contact with oral lesions and needs no trained manpower to collect, making it a suitable bio-fluid of choice for screening. Saliva can be used to detect not only virus, bacteria and other biomarkers but variety of molecular and genetic markers for an early detection, treatment and monitoring cancer and other diseases. The performance of saliva-based diagnostics are reported to be highly (≥95 %) sensitive and specific indicating the test's ability to correctly identify true positive or negative cases. This review focuses on the potentials of saliva in the early detection of not only HPV or other pathogens but also identification of highly reliable gene mutations, oral-microbiomes, metabolites, salivary cytokines, non-coding RNAs and exosomal miRNAs. It also discusses the importance of saliva as a reliable, cost-effective and an easy alternative to invasive procedures.