Squamous Cell Carcinoma Of The Oropharynx Research Articles

Comparative analysis of the expression of р16, PD-L1 in squamous cell carcinoma of the oropharynx and CUP syndrome

Introduction. metastases in the absence of a primary tumor (cancer of unknown primary (Cup) syndrome) are diagnosed in 2–4 % of malignant tumor cases. This pathology is characterized by early metastatic dissemination, weak response to conventional chemotherapy, and aggressive progression. The use of checkpoint inhibitors targeting programmed cell death protein 1 (pD-1) and its ligand (pD-L1) has shown good results in treatment of various cancers including oropharyngeal squamous cell carcinoma (OpSCC). In Cup syndrome, the effectiveness of checkpoint inhibitors is rarely investigated, and pD-L1 expression is often not measured.Aim. To compare the frequency of p16 and pD-L1 hyperexpression in OpSCC and Cup syndrome, and to analyze dependency of survival rates on the level of expression of p16, the most important prognostic marker.Materials and methods. The study included 121 patients (59 with OpSCC and 62 with Cup syndrome) who received medical treatment in the multidisciplinary medical Center “medical City” (Tyumen) and Chelyabinsk Oncological Center of Oncology and Nuclear medicine between 2019 and 2023. Immunohistochemical examination was performed using the vENTANA Benchmark gX with primary antibodies against pD-L1 (clone Sp263, uSA) and р16 (uS Biological, uSA). Statistical analysis of the data was performed using SpSS 26 software. Long-term treatment outcomes were evaluated using 1-, 3-, 5-year survival rates and median survival. Overall survival was analyzed using the kaplan-meier method. Statistical significance of the differences was evaluated using the Cox model.Results. The studied groups did not differ by sex (p = 0.472), age (р = 0.640), and N stage (р = 0.262). patient age in the whole population varied between 42 and 81 years (median age 61.89 ± 11.9 years; mean age 60.81 ± 9.8 years). pD-L1 expression rate was higher in Cup syndrome at 92 % compared to 73 % in OpSCC (statistically significant difference; р = 0.01). Analysis of the association of ORSCC and Cup syndrome with human papilloma virus showed statistically significant difference in p16 hyperexpression: patients with OpSCC had p16-positive status more frequently (53 % of cases) while patients with Cup syndrome mostly had p16-negative status (73 % of cases). mean life expectancy of patients with OpSCC and p16-positive status was 62.65 months (95 % confidence interval 54.98–70.31), minimal observation period was 12 months, maximal was 70 months. mean life expectancy of patients with Cup syndrome and positive p16 status was 66.22 months (95 % confidence interval 56.35–76.10), minimal observation period was 12 months, maximal was 70 months. No statistically significant differences in survival rates of patients with OpSCC and Cup syndrome were found (р = 0.999).Conclusion. The study showed higher pD-L1 expression in patients with Cup syndrome compared to patients with OpSCC: 92 and 73 %, respectively (р = 0.01). The obtained results highlight the importance of routine pD-L1 expression evaluation in patients with Cup syndrome. The frequency of p16 hyperexpression was higher in OpSCC compared to Cup syndrome: 53 % versus 27 % (р = 0.02) which agrees with the worldwide epidemiological data: among all malignant neoplasms of the head and neck, Hpv infection is most common in OpSCC. Therefore, it serves as an important sign of hidden oropharyngeal cancer in Cup syndrome.

A case of metachronous triple primary carcinoma complicated with pulmonary tuberculosis: Case report and review.

Multiple primary malignant neoplasms with tuberculosis are rare. The interaction between tuberculosis and tumor remains unclear. Moreover, the treatment of multiple primary tumors combined with tuberculosis is relatively complicated. Herein, we report a case of metachronous triple primary carcinoma complicated with pulmonary tuberculosis. This report aims to analyze the clinical characteristics of 3 primary tumors combined with tuberculosis. We report the long-term survival of this patient after personalized treatment and this patient have a good quality of life. A 55-year-old male patient was diagnosed with squamous cell carcinoma of the lower thoracic esophagus (cT4bN1M0 IVA) and received concurrent chemoradiotherapy, followed by 2 cycles consolidate chemotherapy. During the follow-up, he was diagnosed with secondary tuberculosis (TB) and accepted anti-TB treatment. During anti-TB treatment, he was diagnosed with squamous cell carcinoma of the oropharynx (cT1N0M0 I P16(-)), then he received radical radiation therapy. However, within a year, the patient was diagnosed with oral squamous cell carcinoma (cT3N0M0 IIIA). He accepted an individualized chemotherapy with paclitaxel combined with capecitabine. Moreover, immunohistochemistry of the patient's 3 biopsies indicated positive P53 expression. Since the patient suffered from esophageal cancer, oropharyngeal cancer, and oral floor cancer, no tumor recurrence or metastasis was observed. And he has a good quality of life. Tuberculosis, TP53 mutation, radiotherapy, smoking, and drinking history may be risk factors for multiple primary tumors. The treatment of multiple primary tumors combined with pulmonary tuberculosis is complicated. Individualized treatment allows patients to achieve long-term survival while also having a good quality of life. Limitations in this case: surgery may be an alternative strategy for the patient, but the patient refused surgery.

Hypofractionated radiation therapy alone for human papillomavirus-related oropharyngeal cancer.

To report a single-institutional experience with hypofractionated radiation therapy alone for human papillomavirus (HPV)-positive oropharyngeal cancer. A total of 101 consecutive patients were treated by radiation therapy alone using a regimen of 66 Gy in 30 fractions (60 patients) or 70 Gy in 33 fractions (41 patients) for newly diagnosed p16-positive squamous cell carcinoma of the oropharynx. Sixty-seven patients (67%) were never smokers. The 3-year actuarial rates of overall survival, local-regional control, and progression-free survival were 94%, 93%, and 89%, respectively. Among never-smokers, the 3-year rates of overall survival and local-regional control were 98% and 100%, respectively. The grade 3+ acute toxicity rate was 21%, with the most commonly observed side effects related to mucositis. Hypofractionated radiation alone resulted in excellent outcomes for patients with HPV-positive oropharyngeal cancer. A prospective clinical trial investigating this modality in the setting of de-escalation is currently underway.

Prognostic Role of Pre- and Post-Treatment [18F]FDG PET/CT in Squamous Cell Carcinoma of the Oropharynx in Patients Treated with Chemotherapy and Radiotherapy.

The prognostic role of imaging with [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in oropharynx cancer (OPC) has been demonstrated in the past. The aim of this study was to assess the prognostic impact of both baseline and post-treatment PET/CT in patients with OPC and treated with chemo- and/or radiotherapy. The PET/CT parameters of scans performed before and after therapy were collected and analyzed to find significant prognosticators for progression-free survival (PFS) and overall survival (OS). Human papillomavirus (HPV) infection's influence on the prognosis was also taken into account. A total of 66 patients were included in the study. The staging volumetric parameters of PET/CT were significant prognosticators for OS, while the same parameters were affordable predictors for PFS at the restaging evaluation. No significant correlations between HPV infection and PET/CT parameters were reported. The prognostic role of volumetric [18F]FDG PET/CT parameters in patients with OPC was reported.

De-escalation treatment of patients with HPV-positive oropharyngeal squamous cell carcinoma.

e18052 Background: According to Globocan in 2020 were identified 98 412 new cases of oropharyngeal squamous cell carcinoma in the world. It was proved that the human papillomavirus (HPV) is a favorable prognostic factor. Patients with HPV-positive oropharynx cancer have higher indicators of progression-free survival (PFS) and overall survival (OS). As induction chemotherapy, the only TPF regimen (cisplatin/ docetaxel/ 5-fluorouracil) has been approved which has high toxic profile. Published results of randomized trials demonstrate the possibility of de-escalation CRT without reduction OS and PFS, but there is no data about safety of de-escalated IC regimen. Given the high toxicity of the standard regimen, as well as the presence of a favorable prognostic factor (HPV infection), since 2021 has started a prospective trial, investigating the possibility of use the dual-component IC regimen according to the TP scheme (cisplatin/ docetaxel). Objective: Improve the results of treatment of patients with locally advanced HPV- positive squamous cell carcinoma of the oropharynx by optimizing the scheme IC. Methods: In the prospective trial included 68 patients with p16-positive oropharyngeal squamous cell carcinoma (T3-4N0-1M0, or T1-4N2-3M0), who were divided into 2 equal groups. The research group received 3 cycles of IC to the de-escalated TP regimen and the control group according to the standard three-component TPF regimen. After completion IC patients of both groups had a standard CRT 70 Gy with carboplatin AUC 2.0 weekly. The primary endpoints were the assessment of objective response rate after the IC and toxicity. The Secondary endpoints: 1-year OS and PFS. Results: Complete response (CR) was achieved in 3 patients (8,8%), a partial response (PR) in 22 (64,7%), stable disease (SD) in 8 (23,5%) patients in the research arm. In the control arm: CR 4 patients (11,8%), PR 24 (70,6%), SD 6 (17,6%) patients. Both IC regimens demonstrated high efficacy rates, and there was no statistically significant ORR in the group (p=0,2133).Toxic manifestations were often observed in the arm of standard IC. The higher incidence of mucositis in the control group was statistically significant (p=0,025). The effect of IC regimen on subsequent CRT was also assessed. In the research arm, the time before the start of CRT was statistically significantly less than in the control arm (30 days vs 63 days, p=0,0035.). And the period of development mucositis of CRT in the TP group was longer than in the TPF group (34G vs 32G, p=0,0298). 1 year - PFS 94%, 1 year - OS 100% in the research group and 92% and 100% in the control arm. There was no statistically significant 1 year – PFS and 1 year - OS in the group (р=0,6547). Conclusions: The research scheme of IC demonstrated high results of an objective response, 1-year OS and 1 year - PFS, comparable to the standard TPF scheme, against the background of better tolerance.

IGSF3 tissue expression in squamous cell carcinoma of the oropharynx: a novel tool for prognosis assessment in HPV-related and HPV-unrelated disease.

Biomarkers are not broadly used in the management of head and neck cancers (HNCs). Biomarkers have been beneficial in the management of other cancers, however, not in HNCs. Therefore, we observed the immunopositivity of a novel biomarker called immunoglobulin superfamily member 3 (IGSF3) in tumor tissues in HPV-related and HPV-unrelated OPSCC. Two patient cohorts (C1 and C2) from separate time periods were available for this study (total N = 282). Both consisted of OPSCC patients treated at the Helsinki University Hospital (HUS, Helsinki, Finland) during 2000-2016. For HPV determination, HPV mRNA in situ hybridization was used. Immunohistochemistry was used to assess IGSF3 immunopositivity in cancer tissues. Overall survival (OS) was used as endpoint in the statistical analysis. In C1, stronger immunopositivity of IGSF3 in tumor-infiltrating lymphocytes (TILs) correlated with favorable OS (p = 0.005). Stronger IGSF3 immunopositivity in tumor cells (TCs) was associated with HPV negativity (p = 0.017). Stronger IGSF3 immunopositivity in TILs correlated with HPV positivity (p < 0.001). Elevated IGSF3 immunopositivity in TILs associates with HPV-related tumors and may signify favorable prognosis. The immunopositivity of IGSF3 differs between HPV-related and HPV-unrelated OPSCC.

Surrogate Endpoints in p16-Positive Squamous Cell Carcinoma of the Oropharynx

Surrogate Endpoints in p16-Positive Squamous Cell Carcinoma of the Oropharynx

ENID: Phase II Trial of Definitive Chemoradiation with Elective Nodal Irradiation Dose De-Escalation for P16 Positive Squamous Cell Carcinoma of the Oropharynx

ENID: Phase II Trial of Definitive Chemoradiation with Elective Nodal Irradiation Dose De-Escalation for P16 Positive Squamous Cell Carcinoma of the Oropharynx

Adjuvant Treatment Deintensification after Transoral Surgery for Human Papillomavirus-Positive Squamous Cell Carcinoma of the Oropharynx

Adjuvant Treatment Deintensification after Transoral Surgery for Human Papillomavirus-Positive Squamous Cell Carcinoma of the Oropharynx

Human Papilloma Virus Positive Oropharyngeal Squamous Cell Carcinoma and the Immune System: Pathogenesis, Immunotherapy and Future Perspectives.

Oropharyngeal squamous cell carcinoma (OPSCC), a subset of head and neck squamous cell carcinoma (HNSCC), involves the palatine tonsils, soft palate, base of tongue, and uvula, with the ability to spread to adjacent subsites. Personalized treatment strategies for Human Papillomavirus-associated squamous cell carcinoma of the oropharynx (HPV+OPSCC) are yet to be established. In this article, we summarise our current understanding of the pathogenesis of HPV+OPSCC, the intrinsic role of the immune system, current ICI clinical trials, and the potential role of small molecule immunotherapy in HPV+OPSCC.

Surrogate endpoints in clinical trials of p16-positive squamous cell carcinoma of the oropharynx: an individual patient data meta-analysis

The increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy. We did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as potential surrogates for overall survival: freedom from local progression, freedom from regional progression, freedom from distant metastasis, freedom from locoregional progression, freedom from any progression, locoregional progression-free survival, progression-free survival, and distant metastasis-free survival. We used a two-stage meta-analytical framework, which requires high correlation between the intermediate clinical endpoint and overall survival at the patient level (condition 1), and high correlation between the treatment effect on the intermediate clinical endpoint and the treatment effect on overall survival (condition 2). For both, an r2 greater than 0·7 was used as criteria for clinically relevant surrogacy. We analysed 1373 patients with oropharyngeal cancer from May 9, 2020, to Nov 22, 2023. 1231 (90%) of patients were men, 142 (10%) were women, and 1207 (88%) were White, with a median age of 57 years (IQR 51-62). Median follow-up was 4·2 years (3·1-5·1). For the first condition, correlating the intermediate clinical endpoints with overall survival at the individual and trial level, the three composite endpoints of locoregional progression-free survival (Kendall's τ 0·91 and r2 0·72), distant metastasis-free survival (Kendall's τ 0·93 and r2 0·83), and progression-free survival (Kendall's τ 0·88 and r2 0·70) were highly correlated with overall survival at the patient level and at the trial-group level. For the second condition, correlating treatment effects of the intermediate clinical endpoints and overall survival, the composite endpoints of locoregional progression-free survival (r2 0·88), distant metastasis-free survival (r2 0·96), and progression-free survival (r2 0·92) remained strong surrogates. Treatment effects on the remaining intermediate clinical endpoints were less strongly correlated with overall survival. We identified locoregional progression-free survival, distant metastasis-free survival, and progression-free survival as surrogates for overall survival in p16-positive oropharyngeal cancers treated with chemotherapy or radiotherapy, which could serve as clinical trial endpoints. NRG Oncology Operations, NRG Oncology SDMC, the National Cancer Institute, Eli Lilly, Aventis, and the University of Michigan.

CT-perfusion in the diagnosis of oropharyngeal cancer and monitoring of chemoradiotherapy.

Purpose of the study: to identify diagnostic effectiveness of the CT perfusion method in diagnosing squamous cell carcinoma of the oropharynx and in assessing dynamic changes in the affected area after chemoradiotherapy.Materials and methods. The results of CT perfusion and CT with intravenous contrast were analyzed in 27 patients aged 40 to 76 years, who were divided into three groups: 1) a control group of patients with suspected oropharyngeal tumors – 9 people (33.4%); 2) group of primary (untreated) patients – 8 people. (29.6%) with a verified diagnosis of squamous cell carcinoma; 3) a group of patients with this diagnosis only after chemoradiotherapy – 10 people (37.0%).Results. Our own algorithm for CT perfusion of the oropharynx region was developed. Digital indicators characterizing the presence of tumor tissue in the tissues of the oropharynx were determined: arterial blood flow (AF) and blood volume (BV). When studying CT perfusion indicators, the following was established: in the group of untreated patients, in contrast to the control group of patients, the values of equivalent blood volume (BV), arterial blood flow velocity (AF) and permeability (FE) were statistically significantly increased. Whereas in patients after chemoradiation treatment, compared with the group of untreated patients, CT perfusion indices were statistically significantly reduced in the following parameters: equivalent blood volume (BV), arterial blood flow velocity (AF). The vascular permeability indicator (FE) is only of secondary importance in identifying the tumor process. Analysis of the results of CT perfusion in patients after chemoradiation treatment revealed an almost complete restoration of tissue perfusion indices in terms of AF and BV relative to perfusion indices in patients in the control group.Conclusion. The results of our study indicate the diagnostic effectiveness of CT perfusion in detecting oropharyngeal cancer and in assessing the corresponding changes in the affected area that occur after chemoradiotherapy. Changes in CT perfusion parameters are associated with microcirculation in the tumor area, which is confirmed by a statistically significant decrease in BV and AF parameters after chemoradiotherapy.

Acute and definitive management of oropharyngeal hemorrhage in patients with squamous cell carcinoma of the oropharynx.

Massive oropharyngeal bleeding post-chemoradiotherapy is a life-threatening condition that requires emergent management. This retrospective case series included 11 patients with oropharyngeal squamous cell carcinoma who suffered from massive bleeding during or following treatment with definitive chemoradiotherapy. Details of acute and definitive management of oropharyngeal bleeding are reported. Nine of 11 hemorrhagic events occurred a mean (SD) of 88.6 days (53.6) after radiotherapy. Airway intubation and embolization were performed in 10 of 11 patients, followed by surgery in 7 of 11 patients. The most commonly embolized vessels were the external carotid and lingual arteries. At the time of discharge, 3 of 11 patients had a tracheostomy, and 7 of 11 continued to use a gastrostomy tube. Four patients died. Hemorrhagic complications in oropharyngeal cancer treatment require emergent responses. Developing a workflow for coordination between multidisciplinary teams can maximize probability of survival and decrease morbidity.

Radiotherapy with or without chemotherapy for locally advanced head and neck cancer in elderly patients: analysis of the Head and Neck Cancer Registry of Japan.

Whether concurrent chemotherapy with radiotherapy (CRT) is effective for elderly patients with head and neck cancer is a controversial topic. This study aimed to analyze the effectiveness of CRT vs. radiation therapy (RT) among elderly patients in Japan. Data from the Head and Neck Cancer Registry of Japan were extracted and analyzed. Patients with locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx who received definitive CRT or RT between 2011 and 2014 were included. CRT was administered to 78% of the 1057 patients aged ≥ 70years and 67% of the 555 patients aged ≥ 75years. For the patients aged ≥ 75years, the overall survival (OS) rate was significantly better in the CRT group than in the RT group (P < 0.05), while the progression-free survival (PFS) rate was not significantly different (P > 0.05). The add-on effect of CRT was significantly poor in elderly patients (P < 0.05), and it was not a significant factor in the multivariate analysis for patients aged ≥ 75years. After propensity score matching, there were no significant differences in the OS and PFS rates between the patients aged ≥ 70years and those aged ≥ 75years (all, P > 0.05). Although aggressive CRT is administered to elderly patients in Japan, its effectiveness is uncertain. Further prospective randomized trials are needed to verify whether CRT is superior to RT alone for elderly patients.

Personalized neck irradiation guided by sentinel lymph node biopsy in patients with squamous cell carcinoma of the oropharynx, larynx or hypopharynx with a clinically negative neck: (Chemo)radiotherapy to the PRIMary tumor only. Protocol of the PRIMO study

BackgroundElective neck irradiation (ENI) is performed in head and neck cancer patients treated with definitive (chemo)radiotherapy. The aim is to eradicate nodal metastases that are not detectable by pretreatment imaging techniques. It is conceivable that personalized neck irradiation can be performed guided by the results of sentinel lymph node biopsy (SLNB). It is expected that ENI can be omitted to one or both sides of the neck in 9 out of 10 patients, resulting in less radiation side effects with better quality of life. Methods/designThis is a multicenter randomized controlled trial aiming to compare safety and efficacy of treatment with SLNB guided neck irradiation versus standard bilateral ENI in 242 patients with cN0 squamous cell carcinoma of the oropharynx, larynx or hypopharynx for whom bilateral ENI is indicated. Patients randomized to the experimental-arm will undergo SLNB. Based on the histopathologic status of the SLNs, patients will receive no ENI (if all SLNs are negative), unilateral neck irradiation only (if a SLN is positive at one side of the neck) or bilateral neck irradiation (if SLNs are positive at both sides of the neck). Patients randomized to the control arm will not undergo SLNB but will receive standard bilateral ENI. The primary safety endpoint is the number of patients with recurrence in regional lymph nodes within 2 years after treatment. The primary efficacy endpoint is patient reported xerostomia-related quality of life at 6 months after treatment. DiscussionIf this trial demonstrates that the experimental treatment is non-inferior to the standard treatment in terms of regional recurrence and is superior in terms of xerostomia-related quality of life, this will become the new standard of care.

S2131 Rare Case of Synchronous Association of Adenocarcinoma of the Ampulla of Vater With Sporadic Squamous Cell Carcinoma of the Oropharynx

S2131 Rare Case of Synchronous Association of Adenocarcinoma of the Ampulla of Vater With Sporadic Squamous Cell Carcinoma of the Oropharynx

Abstract PO-066: Complete pathological response following neoadjuvant chemotherapy and recurrence free survival in patients with p16-positive oropharyngeal cancer

Abstract Introduction: Locoregionally advanced p16+ squamous cell carcinoma of the oropharynx (OPSCC) is most often treated either with primary chemoradiation (CRT) or surgery followed by adjuvant treatment. Surgery alone is often insufficient treatment as adverse features such as extranodal extension, close or positive margins, lymphovascular invasion, or multiple positive lymph nodes are often identified, resulting in the need for adjuvant radiation or CRT. Primary surgery is often not pursued in more advanced cases since surgical pathology may show adverse features requiring adjuvant CRT, resulting in "triple therapy", the effects of which may worsen risk of long-term treatment toxicity. Our institution has demonstrated excellent oncologic and quality of life outcomes using a neoadjuvant chemotherapy (NAC) regimen of cisplatin and docetaxel prior to surgical treatment with TORS and neck dissection. Due to high rates of clinical-to-pathologic downstaging, adjuvant treatment is often avoided entirely. Here, we explore whether the development of a complete pathologic (pCR) response following NAC associates with 2-year recurrence free survival. Methods: A retrospective cohort study of patients receiving neoadjuvant doublet cisplatin and docetaxel followed by surgery (NAC+S) at a single institution between October 2015 and March 2023 was performed and pathologic responses and 2-year recurrence free survival was recorded following IRB exemption. Results: Fifty-four patients with p16+ OPSCC treated with NAC+S were identified. 49 patients (91%) received three cycles of NAC; 5 patients (9%) received two cycles. Comparing clinical staging to pathologic analysis of surgical specimens, 40 of 54 patients (68%) experienced clinical-to-pathologic downstaging after NAC. A pCR was identified in 23 of 54 patients (43%). Of patients that did not develop a pCR, 9 of 31 patients (29%) received adjuvant treatment due to the identification of high-risk pathologic features. Of patients that developed a pCR, 1 of 23 (4%) developed disease relapse within 2 years. Of patients that did not develop a pCR but did not require adjuvant treatment, 2 of 22 (9%) developed disease relapse within 2 years. Of patients that did not develop a pCR but did require adjuvant treatment, 2 of 9 (22%) developed disease relapse within 2 years. A trend toward reduced risk of disease relapse was observed in patients that develop a pCR following NAC compared to those that do not but did not reach statistical significance (1 of 23 relapses with pCR, 4 of 31 relapses without pCR; P&amp;gt;0.05, two-sided Chi-square test). Conclusion: High rates of pCR following NAC were observed in this small retrospective cohort of patients with newly diagnosed p16+ OPSCC despite 84% of patients avoiding any adjuvant treatment. Patients that develop a pCR after NAC trend toward reduced risk of recurrence compared to those that do not. The development of pCR after NAC may be a suitable short-term clinical outcome measure in prospective clinical trials of NAC for patients with newly diagnosed p16+ OPSCC. Citation Format: Alisha R. Pershad, Maxwell Madani, Timothy B. Shaver, Arjun Joshi, Clint T. Allen, Joseph F. Goodman. Complete pathological response following neoadjuvant chemotherapy and recurrence free survival in patients with p16-positive oropharyngeal cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-066.

PD-L1 and p53 expression in squamous cell carcinoma of the oropharynx depending on human papilloma virus status

Introduction. High-risk human papilloma virus (Hpv), especially genotype 16, causes oropharyngeal squamous cell carcinoma (OSCC). It is detected in about 70 % of tumors developing from lymphoid tissue of the tonsils or the base of the tongue. Due to the increased number of Hpv-positive OSCC, Hpv status is considered a marker of OSCC clinical outcome. Easy testing, low cost, reliability, and high sensitivity of immunohistochemical analysis for p16INk4a allowed to widely use this method for Hpv status determination.Aim. To determine the association between programmed death-ligand 1 (pD-L1) and p53 expression and presence of indirect Hpv marker – p16INk4a – in patients with OSCC.Materials and methods. The study included 76 patients with OSCC т1–4N0–3m0 who received treatment at the Republican Specialized Scientific and practical medical Center of Oncology and Radiology (n = 37) and its Tashkent branch (n = 39) between 2015 and 2020. for all selected patients, retrospective immunohistochemical analysis for the presence of p16INk4a, pD-L1 and р53 in tumor samples fixed with formalin in paraffin blocks was performed. In our work, immunohistochemical examination for p16INk4a was the only relevant tool for Hpv status determination. To reinforce its prognostic significance, we used additional molecular markers pD-L1 and p53 which play an important role in carcinogenic transformation and OSCC progression.Results. The results of immunohistochemical analysis showed that p16INk4a overexpression was accompanied by positive pD-L1 reaction in 46 % (6/13) of cases; there were no cases of positive expression of mutant type p53. wild type p53 was identified in only 1 (3 %) case in combination with p16INk4a overexpression.Conclusion. The developed panel consisting of 3 molecular markers (p16INk4a, pD-L1 and р53) may open new horizons in accurate prognosis, risk stratification and understanding of OSCC molecular signature. This, in turn, will help clinicians in selection of individual therapy strategies for treatment de-escalation and outcome optimization.

The effect of smoking on the immediate effectiveness of induction chemotherapy in the combined treatment of HPV-associated oropharyngeal cancer

Purpose. Evaluation of the effect of smoking on the immediate effectiveness (achievement of objective response – OR) of induction chemotherapy in patients receiving combined treatment for locally advanced HPV-positive squamous cell carcinoma of the oropharynx.Patients and methods. Sixty-eight patients (51 men and 17 women) with locally advanced squamous cell cancer of the oropharynx associated with papillomavirus were included in the study, which was carried out from 2021 to 2023 at the P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Moscow, Russian Federation and the Municipal Clinical Oncological Hospital № 1 of the Department of Health of Moscow. The patients were divided into 2 equal groups, fully comparable in terms of the main characteristics (smoking history, stage, histological type, and degree of tumour differentiation). At the first stage, patients of the 1st (main) group received de-escalated induction chemotherapy: three 21-day courses according to the TR scheme (docetaxel in the dose of 75 mg/m2 + cisplatin 75 mg/m2); patients of the 2nd (control) group were treated with standard scheme (docetaxel 75 mg/m2 + cisplatin 75 mg/m2 + 5-fluorouracil 1000 mg/m2). Patients in both groups received prophylactic granulocyte colony-stimulating factor. At the second stage, standard chemoradiotherapy was carried out against the background of drug radiomodification with carboplatin. Correlation analysis was performed by calculating the Spearman coefficient with Bonferroni correction. Differences were considered reliable at p &lt; 0.05.Results. When evaluating the objective response to treatment, it was revealed that disease control was achieved in 33 (97 %) patients from group 1 and in all 34 (100 %) patients from group 2. Complete response was observed in 3 (8.8 %) patients from group 1 and 4 (11.8 %) from group 2; partial regression in 22 (64.7 %) and 24 (70.6 %); stabilisation of the tumour process in 8 (23.5 %) and 6 (17.6 %) respectively. Further analysis showed that there was no direct or inverse correlation between smoking and differentiated level of response (primary lesion, altered lymph nodes); all patients (smokers and those who had never smoked) responded equally effectively to the first stage of combined treatment, regardless of the ICT regimen.Conclusion. In our study, no statistically significant effect of smoking on the immediate effectiveness of induction chemotherapy in the combined treatment of locally advanced HPV-associated squamous cell carcinoma of the oropharynx regardless of the induction regimen was found. However, a longer follow-up period is needed to evaluate the effect of smoking on long-term oncological outcomes.

GWAS-identified telomere length associated genetic variants predict risk of recurrence of HPV-positive oropharyngeal cancer after definitive radiotherapy.

Lymphocyte telomere length (LTL)-related genetic variants may modulate LTL and affect recurrence of squamous cell carcinoma of the oropharynx (SCCOP). A total of 1013 patients with incident SCCOP were recruited and genotyped for 16 genome-wide association study (GWAS)-identified TL-related polymorphisms. Of these patients, 489 had tumour HPV16 status determination. Univariate and multivariate analyses were performed to evaluate associations. Of the 16TL-related polymorphisms, four were significantly associated with LTL: rs1920116, rs3027234, rs6772228, and rs11125529, and the patients with putatively favourable genotypes had approximately 1.5-3 times the likelihood of shorter LTL compared with patients with the corresponding risk genotypes. Moreover, patients with one to four favourable genotypes of the four combined polymorphisms had approximately 3-11 times the likelihood of shorter LTL compared with patients with no favourable genotype. The four LTL-related polymorphisms were significantly associated with approximately 40% reduced risk (for favourable genotypes) or doubled risk (for risk genotypes) of recurrence, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP. Similarly, patients with one to four risk genotypes had significantly approximately 2.5-4 times increased recurrence risk compared with patients with no risk genotype, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP. Four LTL-related polymorphisms individually or jointly modify LTL and risk of recurrence of SCCOP, particularly HPV-positive SCCOP. These LTL-related polymorphisms could have potential to further stratify patients with HPV-positive SCCOP for individualized treatment and better survival. Not applicable.