Treatment Of Oropharyngeal Cancer Research Articles

Transoral Surgery Versus Radiotherapy as Primary Treatment for HPV-Related Oropharyngeal Cancer in the Elderly.

This study compares the oncological outcomes of primary transoral surgery (TOS) and primary radiotherapy (RT) in elderly patients with HPV-related oropharyngeal squamous cell carcinoma (OPSCC). This retrospective cohort study included patients with cT1-2 HPV-related OPSCC from the National Cancer Database (NCDB). A total of 2566 patients were included, with 73.9% receiving primary RT and 22.3% undergoing primary TOS. Subgroup analysis showed a higher 5-year overall survival (OS) rate for primary TOS (81.6%; 95% CI: 79.6%-83.6%) compared to primary RT (70.7%; 95% CI: 68.3%-73.1%), with an adjusted hazard ratio (HR) of 0.64 (95% CI: 0.50-0.81; p < 0.001) after propensity score matching. Notably, only (13.6%) of patients diagnosed in 2020 underwent primary TOS, with a significant decline over the study period. This study suggests that primary TOS may offer better survival outcomes for elderly patients with HPV-related OPSCC compared to primary RT.

The Burden of Recurrent Head and Neck Squamous Cell Carcinoma Across the United Kingdom: Results From a National Snapshot Study.

To investigate the management of recurrent head and neck squamous cell carcinoma (rHNSCC) and describe survival outcomes. Post hoc subgroup analysis of a retrospective national observational cohort was conducted. All patients with rHNSCC who received a definitive treatment decision between September 1, 2021 and November 30, 2021 were included. Survival analysis was stratified according to subsite, primary versus recurrent disease, and surgical versus nonsurgical treatment. Data from 202 rHNSCC patients were derived from a cohort of 1488 patients submitted by 50 UK centers. Median age was 66 years (IQR 58-74), and 142 (70.3%) were male. The most common recurrence subsites were oropharynx (20.5%), oral cavity (19.5%), larynx (16.4%), and hypopharynx (14.9%). Ninety-three (48.4%) were managed curatively. Surgery was the most common treatment for laryngeal (59.4%), oral cavity (60.5%), hypopharyngeal (44.8%), and oropharyngeal (37.5%) cancers. Two-year overall (OS), disease-free (DFS), disease-specific (DSS), and local recurrence free survival (LRFS) were 41.1%, 39.1%, 42.2%, and 39.3%, respectively. rHNSCC treated with surgery had improved OS (p = 0.0005), DFS (p = 0.012), DSS (p = 0.0003), and LRFS (p = 0.007), over nonsurgical treatments. Compared to primary cancers, rHNSCC presents with more advanced T stage (p < 0.001) and distant metastasis (p < 0.001), receives less curative treatment (p < 0.001), and has worse survival outcomes (all p < 0.001). On multivariate analysis, salvage surgery, radiotherapy, and p16 status were independent prognostic factors of all survival outcomes. Recurrent HNSCC is associated with highrates of incurable disease and worse survival than primary cancers. Surgery remains the most common curative treatment in rHNSCC, however future studies are necessary to improve patient selection and optimize outcomes following salvage treatment.

Treatment of oropharyngeal cancer during the COVID-19 lockdown - outcomes for patients treated during the pandemic.

The onset of the coronavirus disease 2019 (COVID-19) outbreak caused major interruptions to the entire healthcare network affecting referral, diagnosis and treatment pathways with the potential to affect cancer treatment outcomes. In Ireland a national lockdown was initiated in March 2020 involving a stay-at-home order with a limitation on travel, social interactions and closure of schools, universities and childcare facilities. We designed a retrospective study comparing treatment outcomes for patients with oropharyngeal cancer treated before and during the COVID pandemic. All patients receiving radical radiotherapy for oropharyngeal cancer pre-COVID (July 17 - July 18) and during COVID (Mar 20 - Mar 21) were included. Patient and disease characteristics, diagnostic timelines, treatment delays and disease outcomes were extracted from the patient record. Disease free survival and overall survival were calculated for both groups. 159 oropharynx patients were included, 76 in the pre-COVID group (Group 1) and 83 in the pandemic group (Group 2). When comparing Group 1 and 2, respectively: There were no differences in human papilloma virus (HPV) status (74% vs. 71% p = 0.795) or Tumour-Node-Metastasis (TNM) overall stage [American Joint Committee on Cancer (AJCC) ed. 8]: (Stage 1: 25% vs. 45.8%, Stage 2: 28.9% vs. 18.1%, Stage 3: 21% vs. 15.7%, Stage 4: 25% vs. 20.5%, p = 0.268). Use of moderate hypofractionated regime increased during the pandemic (2.6% to 10.8%) and one patient omitted chemotherapy due to COVID-related reasons. There was no change in overall treatment times between groups with COVID-related sepsis accounting for one significant delay and one death during treatment. Overall survival at 2 years via Kaplan-Meier analysis; Group 1 cumulative proportion surviving at 2 years was 77% [95% confidence interval (CI): 67-86%] vs. 85% in Group 2 (95% CI: 77-93%, p = 0.35). The disease free survival at 2 years was 69% in Group 1 (95% CI: 59-80%) vs. 76% in Group 2 (95% CI: 67-85%, p = 0.567). In spite of challenges related to the COVID-19 pandemic, we have demonstrated that oropharyngeal cancer patients treatment standards and outcomes were maintained. We did not demonstrate any significant difference in overall survival and disease free survival at 2 years when compared to a similar group prior to the pandemic.

Surgical Treatment of Hypopharyngeal Carcinoma, Neck Dissection and Adjuvant Postoperative Therapy of Oropharyngeal and Hypopharyngeal Cancer: Recommendations of the current S3 Guideline - Part II

Part II of the S3 guideline report deals with the surgical treatment of hypopharyngeal carcinoma, neck dissection for oropharyngeal and hypopharyngeal carcinomas and adjuvant therapy options. Primary surgical therapy ± adjuvant radio- or radiochemotherapy and primary radio- or radiochemotherapy are established as primary therapies for local-regional hypopharyngeal carcinomas. Direct randomized comparisons of both basic therapeutic procedures were never conducted. Available registry data show a worse prognosis of hypopharyngeal carcinoma compared to oropharyngeal carcinomas in all locoregional tumor stages, regardless of the treatment method. For T1N0-T2N0 squamous cell carcinoma of the hypopharynx, there are no relevant differences in overall survival and locoregional relapse rate between primary surgical and primary non-surgical treatment. Primary surgical therapy ± adjuvant radiotherapy or radiochemotherapy and primary radiotherapy or radiochemotherapy are established as primary therapies for advanced but locoregionally limited hypopharyngeal carcinomas. Neck dissection is an integral part of the primary surgical treatment of oropharyngeal and hypopharyngeal cancer. There are only a few randomized studies on non-surgical organ preservation for advanced hypopharyngeal cancer as an alternative to pharyngolaryngectomy, but these have led to the recommendation of alternative concepts in the new guideline. The indication and implementation of postoperative adjuvant radiotherapy and radiochemotherapy for hypopharyngeal carcinoma do not differ from those for HPV/p16-negative and -positive oropharyngeal carcinoma.

Effectiveness of microsurgical palatal tonsillectomy in patients with oropharyngeal cancer and metastases of squamous cell carcinoma into the cervical lymph nodes without identified primary lesion

Introduction. Metastasis without an identified primary lesion is an unresolved and complex problem in clinical oncology. The issue of the necessity of primary lesion identification remains controversial. According to some studies, detection of the primary tumor potentially reduces the dose of radiation therapy and therefore prevents development of toxic reactions that reduce the quality of life of the patient, and in some cases completely eliminates the need for adjuvant therapy. Widespread development and application of robotic, microsurgical, and laser transoral techniques make it possible to verify latent oropharyngeal cancer. The detection of overexpression of p16 protein in metastatic affected lymph nodes may indicate the association of this pathology with human papillomavirus.Aim. To investigate the efficacy of microsurgical palatal tonsillectomy (using a surgical microscope) in diagnosis and treatment of occult oropharyngeal cancer in patients with cervical lymph node metastases of undetected primary site, determine the frequency of expression of the surrogate marker of human papillomavirus – protein p16.Materials and methods. The study was based on the results of diagnosing 82 patients with cervical lymph node metastases of undetected primary site. The inclusion criteria were morphologically verified cervical lymph node metastases of squamous cell carcinoma, absence of a primary tumour after a standard clinical examination. 10 patients underwent palatal tonsillectomy using a surgical microscope and cervical lymph node dissection based on the results of clinical examination and instrumental diagnostics.Results. The use of microsurgical palatal tonsillectomy in patients with metastases of squamous cell carcinoma in the cervical lymph nodes without identified primary lesion allowed to diagnose cancer of the palatine tonsil in 12.1 % of cases, cancer of this location associated with human papilloma virus in 70 % of cases.Conclusion. Microsurgical palatal tonsillectomy using a surgical microscope allowed us to not only verify occult palatine tonsil cancer, but also to establish accurate diagnosis and stage of the disease with subsequent determination of the scope of adjuvant therapy.

Surgical Treatment of Oropharyngeal Cancer - Recommendations of the Current German S3 Guideline, Part I

In general, a trend towards transoral resection (as opposed to classic open approaches) + neck dissection + adjuvant radio- (chemo-) therapy has been observed for oropharyngeal carcinoma over the last 20 years. Techniques of transoral surgery (TOS), including transoral laser microsurgery (TLM) and transoral robotic surgery (TORS) have been propagated in retrospective comparisons with conventional surgery or primary radiochemotherapy as gentle, minimally invasive procedures with good late functional results. Meta-analyses of mostly uncontrolled retrospective analyses suggest that TORS may have better disease-free survival (DFS) and a reduced risk of free flap reconstruction compared with open surgery. TORS (TOS) was associated with fewer tumor-positive resection margins (R1), a lower number of recurrences, fewer intraoperative tracheostomies, a shorter inpatient stay and a shorter duration of postoperative nasal tube feeding compared to open surgery. In principle, based on the best evidence currently available from registry studies, stage I-II oropharyngeal carcinomas can be treated either with primary surgery or radiochemotherapy with a comparable chance of survival. With comparable evidence for stage III and IVa, p16neg. oropharyngeal carcinomas, the majority of authors advocate primary surgery followed by adjuvant radiotherapy or radiochemotherapy as the treatment of first choice. For p16pos. patients the results of registry studies are inconsistent, although the largest registry study on 450 HPV-positive stage III patients shows a significant superiority of primary surgery + adjuvant radiochemotherapy. Since all registry studies did not adjust for smoking status, among other factors, the current data situation should be evaluated with the necessary caution.

Trends in the treatment of human papillomavirus-associated oropharyngeal carcinoma in Slovakia.

The optimal treatment of oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) is currently a subject of clinical research. This questionnaire study investigated current trends in the treatment of HPV-associated (HPV+) OPC in Slovakia with the incorporation of deintensification of oncological treatment into routine clinical practice outside of clinical trials. The Slovak Cooperative Head and Neck Cancer Group (SCHNCG) developed a questionnaire aimed at identifying trends in the oncological treatment of HPV+ OPC intended for all radiation oncology (RO) facilities in Slovakia. Specialists in the field of RO responded to general questions about the character of their individual institutions as well as to 4 theoretical clinical scenarios (case reports) regarding the treatment of HPV+ OPC, focusing primarily on the applied dose of radiotherapy (RT), the extent of target volumes, and the type of concurrent chemotherapy (CHT). The questionnaire study involved 35 RO specialists from 14 institutions in Slovakia. Regarding primary chemoradiotherapy (CRT) in T1N1M0 HPV+ OPC, 16 respondents (45.7%) would consider de-escalation of the RT dose to <70 Gy. In the case of postoperative RT in pT1pN1M0 HPV+ OPC with negative resection margins (R0) and absent extracapsular extension (ECE), 4 physicians (11.4%) would consider de-escalation of the RT dose to <60 Gy in the tumor bed area, while the majority of the treating specialists (n=19, 54.3%) would omit concurrent CHT. In the case of primary RT in elderly patient with T2N1M0 HPV+ OPC, the same number of physicians (n=16, 45.7%) would consider de-escalation of the RT dose to <70 Gy, and 14 respondents (40.0%) would completely omit CHT. In a high-risk patient with T2N3M0 HPV+ OPC with a complete response after 3 cycles of induction chemotherapy (iCHT), none of the respondents would indicate a reduction in the RT dose to the area of the original tumor and lymphadenopathy to <60 Gy. The doses and extent of irradiated volumes in the treatment of HPV+ OPC in Slovakia vary among different institutions. The tendency to de-escalate RT doses and reduce doses of concurrent systemic therapy in Slovakia is high and there was also an observed trend to reduce the extent of radiation treatment fields.

Gd-GQDs as nanotheranostic platform for the treatment of HPV-positive oropharyngeal cancer.

In this study, we developed new gadolinium-graphene quantum dot nanoparticles (Gd-GQDs) as a theranostic platform for magnetic resonance imaging and improved the efficiency of radiotherapy in HPV-positive oropharyngeal cancer. Based on cell toxicity results, Gd-GQD NPs were nontoxic for both cancer and normal cell lines up to 25µg/ml. These NPs enhance the cytotoxic effect of radiation only on cancer cells but not on normal cells. The flow cytometry analysis indicated that cell death mainly occurred in the late phase of apoptosis. The immunocytochemical analysis was used to evaluate apoptosis pathway proteins. The Bcl-2 and p53 protein levels did not differ statistically significantly between radiation alone group and those that received irradiation in combination with NPs. In contrast, the combination group exhibited a significant increase in Bax protein expression, suggesting that cells could undergo apoptosis independent of the p53 pathway. Magnetic resonance (MR) imaging showed that Gd-GQD NPs, when used at low concentrations, enhanced T1-weighted signal intensity resulting from T1 shortening effects. At higher concentrations, the T2 shortening effect became predominant and was able to decrease the signal intensity. Gd-GQD appears to offer a novel approach for enhancing the effectiveness of radiation treatment and facilitating MR imaging for monitoring HPV-positive tumors.

Biomarker-driven radiation therapy dose reduction after transoral robotic surgery for the treatment of HPV-positive oropharyngeal cancer.

TPS6119 Background: HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is a highly curable cancer with a considerable burden of treatment-related toxicities. Transoral surgery (TOS) is a treatment option for patients with early-stage disease; however, adjuvant radiotherapy (RT) is often recommended and can add to these late toxicities. Circulating tumor HPV DNA (ctHPVDNA) is a sensitive marker of tumor recurrence, and undetectable post-operative ctHPVDNA is associated with improved recurrence-free survival. We hypothesize that patients with undetectable post-TOS ctHPVDNA without high risk pathologic factors can safely undergo de-escalation of adjuvant RT to 36 Gy, and this reduction will improve long-term swallowing function. Methods: We opened a multi-institutional phase II study (NCT05387915) including patients with pT1-2, N0-1, M0 HPV-related OPSCC who had TOS resection of their primary site and at least ipsilateral neck dissection. Pertinent inclusion criteria include a &lt;10 pack-year smoking history, or a &lt;30 pack-year smoking history if &gt;10 years since last tobacco consumption, and pathologic findings of one or more intermediate risk factors: close margin (1 – 4 mm), perineural invasion, 2 – 4 positive lymph nodes or a single lymph node &gt;3 cm. Patients with high risk factors (positive margin, extranodal extension, 5 or more positive lymph nodes) are excluded. Patients must have a detectable pre-operative ctHPVDNA and a post-operative ctHPVDNA drawn 7-14 days after TOS; if negative, patients receive 36 Gy of adjuvant RT in 15 fractions of 2.4 Gy delivered daily; if positive, they receive care per the discretion of the treating radiation oncologist. If the final surgical margins at the site of the primary tumor are &gt;2mm, patients are eligible for omission of the primary tumor post-operative bed from the radiation volume. Our primary endpoint is 1-year swallowing function as measured by the composite MD Anderson Dysphagia Index (MDADI) score. Secondary endpoints include overall/progression-free survival and other quality of life metrics. The study is powered to detect an 8.5-point improvement in MDADI composite score at one year over the historical control from ECOG 3311 Arm B. With an alpha of 0.05 and a power of 0.90 we require 27 evaluable patients. Accounting for dropout and patients lost to follow-up, we aim to enroll 35 total patients. Since accrual began in June 2022, we have enrolled 18 patients as of January 2024. We recently opened the study at a second institution and are in the process of opening at a third institution. Clinical trial information: NCT05387915 .

Intra-treatment hypoxia directed major radiation de-escalation as definitive treatment for human papillomavirus-related oropharyngeal cancer.

6007 Background: We previously reported that surgery to the primary site with hypoxia-directed de-escalated radiation to the neck for human papillomavirus associated oropharyngeal carcinoma (HPV+ OPC) can lead to excellent oncologic outcomes. We now report the results of a successor multi-center phase II trial of hypoxia-directed de-escalated chemoradiotherapy without surgery for HPV+OPC. Methods: HPV+ OPC (T0-2/N1-N2c/AJCC 7th) patients were eligible for enrollment. Tumors without evidence of hypoxia on 18F-FMISO (fluoromisonidazole) PET received de-escalated chemoradiation to 30Gy while those with hypoxia received chemoradiation to 70Gy. The primary objective was achieving a 2-year locoregional control (LRC) of 95% (failure was locoregional recurrence where surgical salvage was unfeasible) with a 7% non-inferiority margin. We enrolled a total of 158 subjects upfront to account for a 5% loss due to death (of reasons other than cancer) or follow-up. Secondary objectives were local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS), toxicities, and patient-reported MD Anderson Dysphagia Inventory (MDADI) scores. LF, RF, and DM were estimated using the Cumulative Incidence Function, and OS was estimated using the Kaplan-Meier method. Results were reported up to 1/31/2024. Results: From 4/28/20-4/17/23, 158 HPV+ OPC patients were enrolled where150 patients were eligible for analyses. Patient characteristics: Tonsil (43%); Base of Tongue (47%); unknown primary (10%); &gt;/=10 pack years (22%); T0 (9%), T1 (44%), T2 (47%); N1 (14%), N2a (11%), N2b (59%), N2c (16%). 111 (74%) received 30Gy; 95% cisplatin. With 24 months (8-43) of median follow-up, the 2-year LF, RF, DM rates were 4.2%, 6.9%, 2.0%, respectively. The 2-year overall survival probability was 99%. Only 2 patients could not undergo salvage surgery [one 30Gy (second recurrence); one 70Gy (M1)], both received systemic therapy with durable response. Acute grade 3-4 toxicities were 32% (67% neutropenia). Mean MDADI scores: 92.93 (baseline); 68.24 (3 weeks), 91.45 (4 months) after chemoradiation. Conclusions: These early data indicate that major de-escalation to 30Gy based on hypoxia status achieved significant toxicity reduction without compromise in survival for HPV+ OPC treated with chemoradiation without surgery. Clinical trial information: NCT03323463 .

Characterization of novel compounds that directly bind to and inactivate the HPV E6 protein for treatment of HPV-associated cervical and oropharyngeal cancers.

e15122 Background: The human papillomavirus (HPV) E6 protein is necessary for viral genome replication and is always expressed in HPV-induced malignancies. We performed in silico screening of chemical libraries for molecules that bind to a pocket on the cancer associated HPV-16 E6 protein. We focused on the protein-protein interaction of E6 with one of its cellular binding partners, the ubiquitin ligase E6AP. In a trimolecular complex with E6, E6AP ubiquitinates p53, leading to its destruction by the proteasome. We designed, synthesized, and characterized &gt;300 compounds that 1) bind to the E6AP interaction surface of the HPV-16 E6 protein; 2) are armed with a ‘warhead’ to make an irreversible bond with a specific cysteine in this HPV-16 E6 binding pocket; 3) and restore levels of p53 and selectively decrease viability of HPV-16 expressing tumor derived cells. Methods: E6 inhibitor optimization was guided by in silico docking strategies, co-crystallization, and medicinal chemistry, followed by biochemical and cellular assays to iteratively design and synthesize molecules with increased E6 inhibitory activities. Results: We used whole protein mass spectrometry to interrogate covalent bonding to E6, showing irreversible binding to the cysteine in the targeted E6 binding pocket without the other 13 cysteines in E6, with Ki in the range of seconds. Biolayer interferometry and fluorescence polarimetry measured blockade of E6 with E6AP, with IC50 in the range of 400-600 nM. To establish in cell inactivation of E6, human cervical cancer derived SiHa cells that express HPV-16 E6 were incubated with compounds, showing dose dependent increase of p53 levels up to 8-fold after 24 hrs, an effect that was not observed in the HPV-16- cell line RPE-1 expressing wild-type p53. Viability of two cervical (SiHa, CaSki) and two oropharyngeal HPV-16+ cancer cell lines (UM-SC-47, UM-SCC-104) was reduced with an IC50 of ~2-3 µM, with an IC50&gt;30µM in RPE-1 cells and telomerase immortalized human keratinocytes. These in vitro and cell-based experiments revealed dependence on the cysteine residue in the E6AP binding pocket of E6. For in vivo proof-of-concept studies, we developed mouse xenograft models, performed by engrafting SiHa, UM-SC-47 and UM-SCC-104 cancer derived cells subcutaneously into the flank of immunodeficient mice. Lead compounds were administered by intraperitoneal injection and demonstrated nearly complete inhibition (&gt; 70% tumor reduction) in HPV-16 tumor growth compared to vehicle. Anti-tumor activity was not observed with the HPV-negative tumor cell line C33A. Conclusions: HPV-16 is identified in about 50% of all cervical cancers and the majority of head and neck malignancies. Inactivation of the HPV E6 protein represents the opportunity for a novel molecular targeted approach for medical treatment of HPV-16 expressing cancers of the cervix and oropharynx.

Immunomodulatory extracellular matrix hydrogel induces tissue regeneration in a model of partial glossectomy

While oropharyngeal cancer treatment regimens, including surgical resection, irradiation, and chemotherapy, are effective at removing tumors, they lead to muscle atrophy, denervation, and fibrosis, contributing to the pathogenesis of oropharyngeal dysphagia - difficulty swallowing. Current standard of care of rehabilitative tongue strengthening and swallowing exercises is ineffective. Here, we evaluate an alternative approach utilizing an acellular and injectable biomaterial to preserve muscle content and reduce fibrosis of the tongue after injury. Skeletal muscle extracellular matrix (SKM) hydrogel is fabricated from decellularized porcine skeletal muscle tissue. A partial glossectomy injury in the rat is used to induce tongue fibrosis, and SKM hydrogels along with saline controls are injected into the site of scarring two weeks after injury. Tissues are harvested at 3 and 7 days post-injection for gene expression and immunohistochemical analyses, and at 4 weeks post-injection to evaluate histomorphological properties. SKM hydrogel reduces scar formation and improves muscle regeneration at the site of injury compared to saline. SKM additionally modulates the immune response towards an anti-inflammatory phenotype. This study demonstrates the immunomodulatory and tissue-regenerative capacity of an acellular and minimally invasive ECM hydrogel in a rodent model of tongue injury.

The Effectiveness of Inflammatory Indexes in Assessing Oropharyngeal Cancer Prognosis

Background: Inflammation has long been a key tenet in the diagnosis and management of malignancies, likely contributing to cancer incidence, staging, and progression. Systemic inflammation, in particular, is often elevated prior to and during cancer development. Systemic inflammation in the context of cancer diagnosis and monitoring is measured by various inflammatory indexes such as the systemic inflammatory response index (SIRI), plasma-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and neutrophil-to-lymphocyte ratio (NLR). We set out to determine the relationship between pre- and post-treatment levels of these inflammatory indexes and the prognosis and outcomes of oropharyngeal cancer (OPC). Methods: A retrospective chart review was performed of 172 patients with OPC who underwent treatment for oropharyngeal cancer at University Medical Center in Lubbock, TX between May 2013 to May 2023. Sites of primary cancer were obtained through chart review. HPV infection status and differentiation of the tumor were noted for each patient. Treatment modalities were classified as surgery, radiation, chemotherapy, or concurrent chemotherapy and radiation. Treatment outcomes were classified based on recurrence and death secondary to disease. The relationships between treatment outcome and the described inflammatory indexes were evaluated. Appropriate parametric tests were selected based on the large number of variables. Results: Pre-treatment SIRI and Albumin levels were positively predictive in determining locoregional recurrence (p = 0.031 and p = 0.039). NLR, SII, and SIRI levels taken at three months post-treatment were also found to be positively predictive of locoregional recurrence (p = 0.005, p &lt; 0.0005, and p = 0.007). SIRI taken at six months post-treatment was also found to be positively predictive of locoregional recurrence (p = 0.008). SII at six months post-treatment was found to be positively predictive of survival (p = 0.027). Conclusion: This study suggested that post-treatment levels of several inflammatory indexes, particularly SIRI, NLR, and SII, may be useful in determining the long-term outlook and recurrence of head and neck cancer following treatment.

Outlining treatment methods and limitations for oropharyngeal cancer

Oropharyngeal cancers are a prevalent form of the disease that affects approximately 1 in 60 men and 1 in 140 women. The tonsils are the most common site of oropharyngeal cancer, accounting for 23.1% of all cancers in this region [1]. In over 50% of oropharyngeal squamous cell carcinomas (OPSCC), the p53 gene is mutated [2,3]. This mutation on chromosome 17q13 can lead to a lack of growth control which prevents cells from responding to stress or DNA damage [2,3]. This viewpoint explores risk factors that are increasing the prevalence of OPSCC. Novel approaches for clinical treatment of oropharyngeal cancers are reviewed and compared to current treatments. Limitations for all treatment methods are discussed, demonstrating the need for continued research in the field.

Biomarker-Driven Radiation Therapy Dose Reduction after Transoral Robotic Surgery for the Treatment of HPV-Positive Oropharyngeal Cancer

Biomarker-Driven Radiation Therapy Dose Reduction after Transoral Robotic Surgery for the Treatment of HPV-Positive Oropharyngeal Cancer

145 Survival outcomes of elderly patients treated with a curatively-intended treatment for HPV-related oropharyngeal cancer: a multicenter cohort study

145 Survival outcomes of elderly patients treated with a curatively-intended treatment for HPV-related oropharyngeal cancer: a multicenter cohort study

155 Treatment of oropharyngeal cancer during lockdown - outcomes for patients treated during the pandemic

155 Treatment of oropharyngeal cancer during lockdown - outcomes for patients treated during the pandemic

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.

Ascorbic acid induces ferroptosis via STAT3/GPX4 signaling in oropharyngeal cancer

Ferroptosis is recognized as a new type of regulated cell death initiated by iron-dependent accumulation of lipid peroxidation. Recent studies have shown that the administration of ascorbic acid (AA) preferentially kills tumor cells by impairing iron metabolism and exerting pro-oxidant effects. Despite mounting evidence indicating the anticancer potential of AA, the underlying molecular mechanisms remain unknown. In this study, we demonstrated that AA decreased cell viability and Ki67 expression, along with its accumulation in the G0/G1 phase in FaDu and SCC-154 cell lines. Furthermore, AA exposure induced morphological changes in mitochondria associated with ferroptosis. AA-induced ferroptosis is accompanied by depletion of glutathione (GSH) and increased levels of ferrous ions (Fe2+), reactive oxygen species (ROS), and malondialdehyde (MDA). However, these ferroptotic effects were ameliorated by deferoxamine and N-acetylcysteine. Network pharmacology results showed that signal transducer and activator of transcription 3 (STAT3) is a key target of AA against oropharyngeal cancer. AA markedly downregulates the relative mRNA expression of STAT3 and glutathione peroxidase 4 (GPX4). Immunoblotting indicated that the protein levels of p-STAT3, STAT3, and GPX4 in FaDu and SCC-154 cells decreased significantly in response to AA treatment. Mechanistically, a chromatin immunoprecipitation assay confirmed that AA exposure reduced STAT3 expression in the GPX4 promoter region. Additionally, AA-induced inhibition of cell growth and ferroptosis was suppressed by STAT3 and GPX4 overexpression, respectively. In summary, AA inhibited oropharyngeal cancer cell growth in vitro by regulating STAT3/GPX4-mediated ferroptosis, which may provide a novel theoretical basis for the clinical treatment of oropharyngeal cancer with AA.

CompARE: study protocol for a phase III randomised controlled platform trial comparing alternative regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer

BackgroundPatients with intermediate and high-risk oropharyngeal cancer (OPC) have poorer response to standard treatment and poorer overall survival compared to low-risk OPC. CompARE is designed to test alternative approaches to intensified treatment for these patients to improve survival.MethodsCompARE is a pragmatic phase III, open-label, multicenter randomised controlled trial with an adaptive multi-arm, multi-stage design and an integrated QuinteT Recruitment Intervention. Eligible OPC patients include those with human papillomavirus (HPV) negative, T1–T4, N1–N3 or T3–4, N0, or HPV positive N3, T4, or current smokers (or ≥ 10 pack years previous smoking history) with T1–T4, N2b–N3. CompARE was originally designed with four arms (one control [arm 1] and three experimental: arm 2—induction chemotherapy followed by arm 1; arm 3—dose-escalated radiotherapy plus concomitant cisplatin; and arm 4—resection of primary followed by arm 1). The three original experimental arms have been closed to recruitment and a further experimental arm opened (arm 5—induction durvalumab followed by arm 1 and then adjuvant durvalumab). Currently recruiting are arm 1 (control): standard treatment of 3-weekly cisplatin 100 mg/m2 or weekly 40 mg/m2 with intensity-modulated radiotherapy using 70 Gy in 35 fractions ± neck dissection determined by clinical and radiological assessment 3 months post-treatment, and arm 5 (intervention): one cycle of induction durvalumab 1500 mg followed by standard treatment then durvalumab 1500 mg every 4 weeks for a total of 6 months. The definitive and interim primary outcome measures are overall survival time and event-free survival (EFS) time, respectively. Secondary outcome measures include quality of life, toxicity, swallowing outcomes, feeding tube incidence, surgical complication rates, and cost-effectiveness. The design anticipates that after approximately 7 years, 84 required events will have occurred to enable analysis of the definitive primary outcome measure for this comparison. Planned interim futility analyses using EFS will also be performed.DiscussionCompARE is designed to be efficient and cost-effective in response to new data, emerging new treatments or difficulties, with the aim of bringing new treatment options for these patients.Trial registrationISRCTN ISRCTN41478539. Registered on 29 April 2015