Squamous Cell Carcinoma Of Oropharynx Research Articles

Predictive analysis of clinical features for HPV status in oropharynx squamous cell carcinoma: A machine learning approach with explainability

Predictive analysis of clinical features for HPV status in oropharynx squamous cell carcinoma: A machine learning approach with explainability

Abstract A007: Transient elevation of ctHPVDNA in human papilloma virus-mediated oropharynx squamous cell carcinoma patients following diagnostic surgical procedures

Abstract Background: Circulating tumor DNA (ctDNA) is now widely used across a variety of malignancies as a viable “liquid biopsy” method, with applications in early detection, treatment response evaluation, prognostication, and recurrence monitoring. Recently, ctDNA derived from the tumor-integrated HPV (ctHPVDNA) has borne promising results in HPV-associated cancers, including HPV+ oropharyngeal squamous cell carcinoma (OPSCC). Studies indicate that undetectable ctHPVDNA after complete surgical excision in HPV+ OPSCC corresponds with improved prognosis. However, ctHPVDNA kinetics after diagnostic procedures such as transoral robotic surgery (TORS) in head neck squamous cell carcinoma from an unknown primary (HNSCCUP) or unknown primary has not been extensively studied. The purpose of this study is to show an unexpected trend in NavDx levels following these procedures. Methods: Patients undergoing TORS at Stanford University (September 2023 and August 2024) were prospectively screened and enrolled. A commercially available ctHPVDNA assay (NavDx) was collected at baseline, immediate postoperative (24-48 hours), 7-14 days following surgery, 3 months post- treatment and every 3 months thereafter up to 12 months. Results: Eight patients presented with HNSCCUP, 87.5% (7/8) had detectable baseline ctHPVDNA levels ranging from 2 to 1237. 75% (6/8) of the patients were confirmed p16+ by immunohistochemistry (IHC), while 25% (2/8) tested HPV+ by in situ hybridization (ISH). Diagnostic TORS was performed in 75% (6/8), while 25% (2/8) underwent direct laryngoscopy, with all primary tumors found in the oropharynx, 100% (8/8). Notably, 85.7% (6/7) of patients showed an unexpected elevation in total tumor mutational volume (TTMV) scores post-diagnostic procedure compared to baseline, with ctHPVDNA levels ranging from 30 to 2466, including one case where levels nearly quintupled. One patient had no post-diagnostic procedure TTMV score due to a negative baseline. However, in one other case, there was a negative post-procedure level. Among those with elevated post ctHPVDNA, 71.4% (5/7) underwent complete TORS excision, resulting in decreased postoperative ctHPVDNA levels in all patients, consistent with recent studies. Conclusion: This study provides insight that diagnostic procedures, such as TORS or direct laryngoscopy, in patients with p16+ HPV-mediated oropharyngeal cancer may lead to transient and unexpected elevations in ctHPVDNA levels, measured by TTMV scores. Although most patients showed a subsequent decrease in ctHPVDNA levels following a complete tumor resection, the observed post-diagnostic elevation emphasizes the importance of considering the timing of ctHPVDNA measurements. These findings suggest surgical manipulation may temporarily influence ctHPVDNA kinetics that could impact clinical decision-making and postoperative monitoring. Further research is needed to understand the implications of these transient elevations and optimizing the timing of ctHPVDNA assessments in clinical practice. Citation Format: Hlu Vang, Joanne Soo, Nikita Bedi, Andrea Garofalo, Michelle M Chen, Andrey Finegersh, Floyd Christopher Holsinger. Transient elevation of ctHPVDNA in human papilloma virus-mediated oropharynx squamous cell carcinoma patients following diagnostic surgical procedures [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A007.

Uncommon and Challenging Phenotypes of High-Risk Human Papillomavirus-Associated Head and Neck Carcinomas Revealed by High-Throughput Studies.

HPV- associated squamous cell carcinoma (SCC) is uncommon in non-oropharynx sites and not well characterized. This study aims to investigate uncommon phenotypes of HPV-associated head and neck carcinoma, the prevalence and morphologic spectrum of HPV-associated SCC in the oral cavity, larynx and hypopharynx. P16 immunostaining and HPV E6/7 in situ hybridization (ISH) were performed on tissue microarrays comprised of SCCs from different anatomic sites: oropharynx (n = 270), hypopharynx (n = 52), oral cavity (n = 95) and larynx (n = 123). Tumors were classified as HPV-associated based on a positive E6/7 ISH testing. RNA sequencing was performed on several selected cases. 66% oropharynx SCCs (OPSCCs) were HPV-associated; all were p16/HPV testing concordant except one which was p16 negative. The p16-/HPV + OPSCC resembled similar gene expression signature with p16+/HPV + OPSCCs by transcriptome analysis. 6/95 (6%) oral cavity SCCs were HPV-associated, all from male patients and 5/6 (83%) arose from the floor of mouth. Morphologically, 3/6 (50%) showed keratinizing SCC and 5/6 (83%) demonstrated HPV-associated squamous dysplasia in adjacent mucosa. 1/123 (less than 1%) larynx SCCs and 0/52 hypopharynx SCCs were HPV-associated. Although uncommon, p16 negative HPV-associated OPSCC can occur, emphasizing the importance of judicious HPV testing. The morphology of HPV-associated oral cavity SCCs may deviate from prototypic nonkeratinizing SCC, making them difficult to recognize. Presence of HPV-associated squamous dysplasia could serve as a morphologic clue.

Classification and Treatment of Complications Related to Titanium and Biodegradable Miniplates Using the Lip-Split Transmandibular Approach for Oral and Oropharyngeal Oncological Surgery.

There is a lack of classified definitions and corresponding treatment principles for complications related to titanium miniplate (TMP) and biodegradable miniplate (BMP). This study proposes a classification system for complications related to TMP and BMP osteosynthesis and evaluates the effectiveness of the classification system in the treatment of the complications. One hundred forty-two patients with advanced-stage oral cavity and oropharynx squamous cell carcinoma (SCC) underwent oncological surgery via lip-split transmandibular (LTM) approach including midline, paramedian, stair-step, and triangle. 54.9% of patients were treated with TMP, and 45.1% were treated with BMP for osteosynthesis. The classification of complications is divided into grades 0, 1, 2, and 3. Grade 0 is defined as having no complications. The evaluation criteria for treating complications were significant improvement, partial improvement, and no improvement. All patients underwent en bloc resection of the tumor with histologically negative margins via the LTM approach. The overall success rate of the flap is 98.6%. 25.3%, 48.6%, 14.8%, and 11.3% of patients were treated with midline, paramedian, stair-step, and triangular osteotomy approaches, respectively. A significant increase in the number of paramedian osteotomies was observed compared with other types of osteotomy (P < 0.05). Grades 0, 1, 2, and 3 developed in 54.2%, 12.0%, 14.8%, and 19.0% of patients, respectively. No significant differences in the grade of complications were observed between the TMP group and the BMP group. Sixty-five patients with complications, grades 1, 2, and 3 occurred in 26.2%, 32.3%, and 41.5% of patients. The midline, paramedian, stair-step, and triangle osteotomy approaches were used in 26.1%, 47.7%, and 10.8%, respectively. The incidence of complications in the paramedian osteotomy was significantly higher than that in the other osteotomy (P < 0.05). 83.1% of patients showed significant improvement, 10.8% showed partial improvement, and 6.1% showed no improvement. No significant differences in the treatment outcomes were observed between the TMP group and the BMP group. The incidence of complications in paramedian osteotomy is also significantly higher than 3 types of osteotomy, and 83.1% of patients showed significant improvement in complications. The complication classification system related to TMP and BMP osteosynthesis are easy to implement and feasible in clinical practice.

Neoadjuvant immunotherapy for oropharynx cancer: Correlative studies and long-term outcomes from the CIAO trial.

6059 Background: CIAO (Checkpoint Inhibitors Assessment in Oropharynx cancer) was a window of opportunity trial evaluating the anti-PD-L1 durvalumab (durva) with or without the anti-CTLA-4 tremelimumab (treme) prior to surgery in 28 oropharynx squamous cell carcinoma (OPC) patients (pts). Here we report correlative analyses and long-term survival outcomes. Methods: A total of 28 OPC pts were randomized to receive durva (n=14) or durva plus treme (n=14) for 2 cycles prior to surgery. Adjuvant radiotherapy with or without concomitant chemotherapy was recommended based on pathology findings, per standard of care. Efficacy and safety results have been previously reported. Whole exome sequencing (WES), RNA sequencing (seq), and TCR-seq were performed on available pre- and post-treatment primary tumor specimens. Circulating HPV was quantified pre-treatment and longitudinally. Associations with objective response (OR) to therapy per RECIST were determined using either Fisher’s exact test (binary variables) or rank-sum test (continuous variables). Multiple comparisons were corrected for by the Benjamini and Hochberg method. Disease-free survival (DFS) was defined as the time from surgery to recurrence or death. Results: Of the 28 enrolled pts, 20 were newly diagnosed and 8 had locoregional recurrent disease; 25 were HPV-positive. The OR rate per RECIST was 43%. Efficacy was equivalent in both arms. Responders tended to be of younger age (p=0.02). At the DNA level, baseline tumor mutation burden was not associated with response, but mutational contraction post-treatment was more often observed among responders (p=0.02). There were no statistically significant differentially expressed genes between responders and non-responders, however, immune deconvolution revealed that a low inferred tumor neutrophil-to-leukocyte ratio was associated with response (p=0.01). TCR-seq revealed 8 TCR motifs enriched in responders at 25% false discovery rate. Serum HPV levels significantly decreased in responders after treatment (p=0.02). With a median follow-up from surgery of 59.6 months (range 14.9-71.5 months; data cut-off 1/19/24), none of the 20 patients with newly diagnosed OPC had recurrence and all remain alive at the last contact date (DFS=100%). Of the 9 patients with recurrent OPC, 3 had subsequent distant recurrence and died of disease (median DFS=5.7 years, overall DFS=66.7%). Conclusions: Responses to neoadjuvant checkpoint inhibitors was associated with tumor mutational contraction and a low baseline neutrophil-to-leukocyte ratio in OPC. Eight TCR motifs were enriched in responders. Serum HPV level dynamics was associated with tumor burden and may be useful in response monitoring. DFS outcomes were favorable in both newly diagnosed and recurrent cohorts.

Fibroblasts from HPV-negative oropharynx squamous cell carcinomas stimulate the release of osteopontin from cancer cells via the release of IL-6.

HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) shows distinct biological and clinical behaviour when compared to HPV-negative OPSCC. The overall role of the tumour microenvironment (TME) in head and neck cancer progression and metastasis has been studied intensively, but differences in HPV-negative and HPV-positive OPSCCs are less understood. To investigate the role of cancer-associated fibroblasts (CAFs) and the functional interactions of normal tonsil fibroblasts (NTFs) and OP CAFs with HPV+ and HPV- OPSCC cells and explore novel candidates in tumour-fibroblast crosstalk. A retrospective cohort of 143 primary OPSCCs was characterised using HPV16/18 RNAScope assay, p16 IHC and ɑ-SMA. Four OPSCC, three NTF and 2 new OPSCC CAF cultures were used to assess the cytokine-based interactions using cytokine arrays on conditioned media (CM), followed by co-culture approaches to identify the role of individual cell types and the role of OPN (SPP1) and IL-6 in SCC/fibroblast communication. HPV status was associated with better overall survival. Although ɑ-SMA expression was observed in both OPSCC subtypes, it provided survival stratification only in the HPV-positive group (Log-Rank p = 0.02). Three normal tonsillar fibroblast cultures (NTFs) were characterised by induction of myofibroblastic and senescent phenotypes with similar reactivity to our published NOF phenotype. The OPSCC-derived CAF cultures were characterised and their baseline myofibroblastic and senescence phenotypes varied. Cytokine array analysis of CM to identify novel candidates in the crosstalk between OPSCC tumour cells and NTFs/CAFs identified differences in the cytokine profiles on comparison of HPV+ and HPV- OPSCC cells. Osteopontin (OPN/SPP1) was identified, particularly in HPV-negative OPSCC cell analyses. We have demonstrated that OPN was produced by the OPSCC cells and revealed an associated upregulation of IL-6 in fibroblasts. Treatment of NTFs with rOPN showed alteration in phenotype, including increased contraction and IL-6 production. Antibody-mediated inhibition of CD44v6 attenuated the production of IL-6 by OPN in NTFs. This investigation with OPSCC fibroblasts provides novel insights into the role of CAFs in OPSCC mediated by IL-6 stimulated release of OPN from HPV negative OPSCC cells. The details of HPV-positive SCC cell/fibroblast cytokine crosstalk remain elusive.

Association of adjuvant radiation and survival in human papilloma virus-positive oropharynx squamous cell carcinoma with lymphovascular invasion as the sole adverse pathologic feature.

Postoperative radiotherapy radiation therapy (PORT) for early-stage human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) with positive lymphovascular invasion (LVI) has an unclear association with overall survival (OS). This retrospective cohort study queried the National Cancer Database for surgically treated, T1-2, N0-1 HPV+ OPSCC from 2010 to 2019. Primary exposures were LVI and PORT, and the main outcome was 5-year OS. Odds ratios and hazard ratios (HR) with 95% confidence intervals (CIs) were generated using multivariable models and Cox proportional hazard models, respectively. Of 2768 patients, average age was 59.3 years, 2207 (79.7%) were male, and 386 (13.9%) had LVI. Of patients with LVI as their sole adverse pathologic feature, 220 (57.0%) received PORT, which was not associated with 5-year OS (HR, 1.13; CI, 0.65-1.19). Patients with surgically treated, early-stage HPV+ OPSCC and positive LVI as their only pathologic adverse feature may not require PORT.

The art of specimen orientation: Two-dimensional maps for oropharynx squamous cell carcinoma.

The goal of surgical treatment for oropharynx squamous cell carcinoma (SCCa) is resection to negative margins. Current methods of orienting resection specimens often do not give a comprehensive view, especially in oropharynx SCCa where specimens can lack anatomic landmarks. We created standardized two-dimensional maps of oropharynx anatomy drawn to scale to improve communication between surgeons and pathologists. Notes regarding surgery including anatomic landmarks, areas of concern, additional margins, and relevant clinical information were added to the map. The maps guided pathology work-up, and the pathologist could communicate details back to the surgeon on how the specimen was sectioned or locations of microscopic foci to direct future treatment and clinical monitoring. The use of two-dimensional maps for oropharynx SCCa specimens offers a standardized solution to address the challenges of anatomic orientation. These maps summarized key pathological information, preserved clinical details from the specimens, and guided multidisciplinary conferences when planning adjuvant treatment.

Circulating tumor HPV DNA assessments after surgery for human papilloma virus-associated oropharynx carcinoma

PurposeTo understand the utility of circulating tumor human papillomavirus DNA (ctHPVDNA) blood testing for HPV-associated oropharynx squamous cell carcinoma (HPV + OPSCC) after definitive surgery. Materials and methodsProspective cohort study of HPV(+)OPSCC patients with ctHPVDNA test data to assess its accuracy in detecting biopsy-confirmed disease at various post-treatment time points. Eligible patients had p16(+)/HPV(+) OPSCC and ctHPVDNA testing performed at any time pre-operatively and/or postoperatively. In cases of recurrence, patients were excluded from analysis if ctHPVDNA testing was not performed within 6 months of biopsy. Results196 all-treatment-type patients had at least one PT ctHPVDNA test. The initial post-treatment (PT) ctHPVDNA sensitivity, specificity, PPV, and NPV were 69.2 % (9/13), 96.7 % (177/183), 60.0 % (9/15), and 97.8 % (177/181). 61 surgery alone (SA) patients underwent 128 PT tests. The initial PT SA ctHPVDNA sensitivity, specificity, PPV, and NPV were 100 % (2/2), 96.0 % (48/50), 50 % (2/4), and 100 % (48/48). 35 of 61 (57.4 %) SA patients had NCCN-based histopathologic indications for adjuvant (chemo)radiation but declined. 3 of 35 (8.57 %) had a positive PT ctHPVDNA test of which 1 of 3 (33 %) had biopsy-proven recurrence. Prospectively, ten patients had a PreT positive ctHPVDNA, underwent SA, refused adjuvant treatment, had an undetectable ctHPVDNA within 2 weeks of SA, and remained free of disease (mean 10.3 months). ConclusionThe high specificity and NPV of ctHPVDNA after SA suggest ctHPVDNA may have a role in determining the omission of PT adjuvant (chemo)radiation in select patients.

Treatment Modality Impact on Patient-Reported Quality of Life in Human Papilloma Virus-Associated Oropharyngeal Carcinoma.

To prospectively compare the impact of treatment modality on patient-reported quality of life (QOL) in human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC). Prospective cohort study. Academic medical center. One hundred one patients with American Joint Committee on Cancer (AJCC) 8th edition T1-3 N0-2 HPV + OPSCC completed the European Organization for Research and Treatment of Cancer Quality of Life Core questionnaire and Head and Neck Module pretreatment and 3-month and 1-year posttreatment. Mean score changes were compared to published minimal clinically important differences. Patients underwent surgery alone (SA: N = 42, 42%), surgery with adjuvant radiation (S-RT: N = 10, 10%), surgery with adjuvant chemoradiation (S-CRT: N = 8, 8%), definitive radiation (RT: N = 11, 11%), or definitive chemoradiation (CRT: N = 30, 30%). SA, S-[C]RT, and [C]RT patients all reported clinically significant difficulty with sense of taste/smell persisting at 1 year. S-[C]RT and [C]RT patients reported statistically and clinically significant worse salivary dysfunction and problems with social eating at 1 year than SA. S-[C]RT patients reported statistically and clinically significant worse fatigue and head and neck pain compared to [C]RT and SA patients at 3 months, but normalized at 1 year. S-CRT compared to S-RT had statistically and clinically worse physical and role functioning and swallowing difficulties at 3 months but this difference was resolved by 1-year posttreatment. HPV + OPSCC patients after SA report the lowest posttreatment QOL impact, whereas after S-CRT report the highest symptom burden. Careful selection for definitive surgery is important given the possibility of adjuvant CRT. Patients can experience persistent sense taste and smell difficulties at 1 year with all treatment modalities. 3 Laryngoscope, 134:1687-1695, 2024.

A comparison of loco-regional relapse pattern in HPV positive vs negative oropharyngeal cancers following radiotherapy; relation to pretreatment FDG-PET and radiotherapy target volumes

Background Previous studies have shown that a large proportion of relapses in head-and neck squamous cell carcinoma (HNSCC) following radiotherapy (RT) occur in the pretreatment FDG-PET avid volume (GTV-PET). The aim of the current work was to see if this was valid also in an oropharynx squamous cell carcinoma (OPSCC) only population, and to compare the loco-regional relapse pattern between HPV positive and HPV negative patients. Material and methods Among 633 OPSCC patients treated between 2009 and 2017, 46 patients with known HPV (p16) status and isolated loco-regional relapse were included. Oncologists contoured relapse volumes (RV) on relapse scans (PET/CT, CT or MR), which were thereafter deformed to match the anatomy of the planning CTs. The point of origin (center of volume) of the deformed RVs were determined and analyzed in relation to the RT target volumes (GTV-PET, GTV and CTVs). The relapse pattern was compared between HPV positive and HPV negative patients using Fischer’s exact test. Results Sixty RVs were contoured in the 46 patients. 55% (95% CI 44–67%) of relapses originated in GTV-PET, while the other RT volumes harbored 12% (5–20%) (GTV), 18% (9–28%) (high risk CTV) and 5% (0–11%) (low risk CTV) of relapses. Six relapses were found outside the RT target volumes. No significant difference in relapse pattern between HPV positive and HPV negative patients was found (p = .95). Conclusion There were no signs of difference in loco-regional relapse pattern between HPV positive and HPV negative patients. In agreement with previous findings, GTV-PET was the most frequent RT target volume of relapse.

Comparison of Safety and Efficacy of Two Different Chemotherapy Dosing Schedules Used in Concurrent Chemoradiation of Head and Neck Cancer: A Retrospective Experience from a Tertiary Cancer Care Institute of Eastern India

Introduction: Concurrent chemoradiation has shown improvements in local control and survival in various multi-institutional trials and been the standard of care for locally advanced head and neck cancers. Platinum-based chemotherapy has shown the maximum benefit without any significant difference between mono- or polychemotherapy. Despite a general consensus that platinum-containing regimens are optimal, the actual dose schedule remained open questions. Our study aimed to assess the efficacy and toxicity of concurrent weekly cisplatin with radical radiotherapy and compare two different chemotherapy dosing schedules of concurrent chemoradiation in head and neck cancer. Materials and methods: The records of 62 eligible patients of locally advanced (T3-4a, N1-2) squamous cell carcinoma of oropharynx, hypopharynx and larynx registered between 2016 to 2020 at a regional cancer centre in India were analysed from the hospital database after approval of the Institutional Ethical Committee and informed consent taken from all the eligible patients.One group of patients (Group A) received Concurrent Chemo-radiation with injection Cisplatin 40 mg/m2 weekly with Radiotherapy to a dose of 66 Gy delivered in 33 fractions for six &amp; half weeks and the patients of the other group (Group B) received injection Cisplatin 100 mg/m2 in three weekly schedule on Days 1, Day 22 &amp; Day 43 along with the same radiation schedule. Results: There was no significant difference in the baseline characteristics between the two groups (p value≥0.05). Though the complete response occurred more in 3 weekly group compared to weekly cisplatin group at follow up of 6 weeks (67.7% vs 61.3%), 6 months (80.6% vs. 67.7%) and 12 months from the completion of CCRT (78.9% vs 65%), it was not statistically significant (p value≥0.05). No statistically significant differences were found in terms of both the acute toxicities (anaemia, leukopenia, mucositis, dermatitis, UGI toxicities, dysphagia) and late toxicities (laryngeal edema, dryness of mouth and edema of skin of neck) when weekly concurrent chemoradiotherapy was compared to three weekly chemoradiotherapy (p value ≥ 0.05).Conclusion: Weekly chemotherapy regimen can be delivered safely on a day care basis and can be helpful in a set up with limited logistics and considerable patient burden.&#x0D;

A prospective evaluation of neck and shoulder function following treatments of early-stage human papillomavirus-associated oropharynx cancer.

To compare post-treatment neck and shoulder function between human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC) treatments. Prospective, repeated-measures study. Tertiary care center. Treatment-naïve patients with American Joint Committee on Cancer eighth edition stage T0-3/N0-2 HPV+OPSCC. Patients completed the Neck Dissection Impairment Index (NDII) pre-treatment and 3-months and 1-year post-treatment. The NDII assesses 10 neck and shoulder functions scored 0-5 (total score 0-100), with higher scores suggesting better function. A total of 106 patients underwent: surgery alone (SA, n = 46, 43%), surgery with adjuvant radiation ± chemotherapy (S + a[C]XRT, n = 18, 17%), or definitive radiation ± chemotherapy (d[C]XRT, n = 42, 40%). cTN classification and pre-treatment NDII scores did not differ between groups. SA patients reported worsened 3-month post-treatment versus pre-treatment self-care (4.6 vs. 5.0), lifting light (4.6 vs. 5.0) and heavy (4.2 vs. 4.8) objects, overhead reach (4.5 vs. 4.9), activity (4.5 vs. 4.9), socialization (4.7 vs. 4.9), recreation (4.6 vs. 4.9), and overall score (86.8 vs. 95.3) (all p < 0.05). One-year post-treatment scores (n = 34) were no different than pre-treatment in all domains. S + a[C]XRT patients reported worsened 3-month versus pre-treatment stiffness (4.0 vs. 4.8), lifting heavy objects (3.8 vs. 4.9), overhead reach (4.2 vs. 4.9), socialization (4.6 vs. 5.0), recreation (4.4 vs. 4.9) and overall score (82.4 vs. 96.0) (all p < 0.05). One-year post-treatment scores (n = 13) were no different than pre-treatment in all domains. d[C]XRT patients reported worsened 3-month versus pre-treatment difficulty lifting heavy objects (4.3 vs. 4.7) and recreation (4.3 vs. 4.7). One-year posttreatment scores (n = 21) were no different than pre-treatment in all domains. HPV + OPSCC patients may experience mild shoulder/neck dysfunction 3 months after treatment that usually resolves by 1 year, independent of treatment modality.

Prospective quality of life outcomes for human papillomavirus associated oropharynx cancer patients after surgery alone

PurposeTo evaluate changes in patient-reported quality of life (QOL) to inform treatment decisions for human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC). Materials and methodsPatients with American Joint Committee on Cancer (AJCC) 8th edition cT0-T3 and cN0-N3 HPV + OPSCC treated with transoral robotic surgery to the primary site with neck dissection completed questionnaires prior to surgery and at three-months and one-year post-operatively. Questionnaires included four validated instruments: the University of Washington Quality of Life Questionnaire (UW-QOL), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Head and Neck Module (HN35), and the Neck Dissection Impairment Index (NDII). ResultsForty-eight patients filled out pretreatment and three-month questionnaires. 37 patients filled out one-year questionnaires. With the UW-QOL, at three-months, patients reported a statistically significant and clinically meaningful decreased mean score for appearance that resolved at one-year (presurgery: 92.4, 3-month: 81.0, p < 0.001; one year: 86.5). At three months and one-year, significant and clinically meaningful decreased mean taste scores persisted (presurgery: 98.0; three-months: 76.3, one-year: 80.3; all p < 0.001). With the EORTC QLQ-C30 and HN35, at one-year, only mean scores for sense of taste or smell (one-year: 13.1; p < 0.001) did not return to baseline. With the NDII, patients returned to functions comparable to baseline in all domains. ConclusionPost-treatment quality of life is high for HPV+ OPSCC patients treated with surgery alone. Mild taste and possibly smell dysfunction may continue in some patients. With careful selection, surgery alone for HPV + OPSCC offers favorable QOL outcomes. Lay summaryPatients with HPV+ associated oropharynx cancer treated with surgery alone completed quality of life questionnaires before and after surgery. Quality of life remained high for most patients, with a subset of patients experiencing mild taste dysfunction one-year after surgery.

Association of Suppressive Myeloid Cell Enrichment with Aggressive Oropharynx Squamous Cell Carcinoma.

While immune-cell infiltrated tumors, such as human papillomavirus positive (HPV+) ororpharyngeal squamous cell carcinomas (OPSCC) have been associated with an improved clinical prognosis, there is evidence to suggest that OPSCCs are also subjected to increased immunoregulatory influence. The objective of this study was to assess whether patients with clinically aggressive OPSCC have a distinct immunosuppressive immune signature in the primary tumor. This retrospective case-control study analyzed 37 pre-treatment tissue samples from HPV+ and HPV-negative OPSCC patients treated at a single institution. The cases were patients with known disease recurrence and the controls were patients without disease recurrence. An mRNA-expression immune-pathway profiling was performed, and correlated to clinical outcomes. The TCGA head and neck cancer database was utilized to make comparisons with the institutional cohort. In our cohort, HPV-negative and HPV+ patients with known disease recurrence both had significantly increased suppressive monoctyte/macrophage and granulocyte cell-expression-profile enrichment. Similar findings were found in the TCGA cohort when comparing HPV-negative to positive patients. our study demonstrates that patients with recurrent HPV+ OPSCC had suppressive monocyte/macrophage and granulocyte immune-cell enrichment, similar to those seen in the more aggressive HPV-negative OPSCC.

PREVLAR: Phase 2a Randomized Trial to Assess the Safety and Efficacy of RRx-001 in the Attenuation of Oral Mucositis in Patients Receiving Head and Neck Chemoradiotherapy

No Food and Drug Administration-approved intervention exists for oral mucositis (OM) from chemoradiotherapy (CRT) used to treat head and neck cancers. RRx-001 is a hypoxia-activated, cysteine-directed molecule that affects key pathways involved in OM pathogenesis. This phase 2a, multi-institutional trial was designed to assess the safety and feasibility of 3 schedules of a fixed concentration of RRx-001; a standard-of-care arm was included to identify potential signals of efficacy for further study. This study enrolled patients with oral cavity and oropharynx squamous cell carcinoma receiving definitive or postoperative cisplatin-based CRT. Patients were randomized into 4 cohorts. In arms 1 to 3, RRx-001 was coinfused with patients' blood at differing intervals. Arm 4 was a control cohort of patients treated with CRT alone. Trained evaluators assessed OM using a standardized data collection instrument twice weekly during treatment and then until resolution. OM severity was scored centrally using World Health Organization criteria. Safety outcomes were assessed using National Cancer Institute - Common Terminology Criteriav4 benchmarks. Long-term tumor response was defined by Response evaluation criteria in solid tumors v1.1 criteria. Fifty-three patients were enrolled, with 46 and 45 individuals contributing safety and efficacy data, respectively. There were no severe adverse events attributed to the study drug. Across all 3 active arms, the study drug was infused fully per protocol in 86% of patients. All 3 RRx-001 treatment cohorts appeared to demonstrate a similar or lower OM duration relative to control; arm 1 had the lowest median duration of severe oral mucositis (SOM), 8.5 days versus 24 days in controls among patients who developed at least 1 day of SOM. There were no locoregional failures in any patient. Our results support the safety and feasibility of RRx-001 as an intervention to mitigate SOM. Additional studies are planned to confirm its efficacy.

Ninety-day mortality following transoral robotic surgery or radiation at Commission on Cancer-accredited facilities.

Postoperative mortality for oropharynx squamous cell carcinoma (OPSCC) with transoral robotic surgery (TORS) varies from 0.2% to 6.5% on trials; the real-world rate is unknown. NCDB study from 2010 to 2017 for patients with cT1-2N0-2M0 OPSCC with Charleson-Deyo score 0-1. Ninety-day mortality assessed from start and end of treatment at Commission on Cancer-accredited facilities. 3639 patients were treated with TORS and 1937 with radiotherapy. TORS cohort had more women and higher income, was younger, more often treated at academic centers, and more likely to have private insurance (all p < 0.05). Ninety-day mortality was 1.3% with TORS and 0.7% or 1.4% from start or end of radiotherapy, respectively. From end of therapy, there was no significant difference on MVA between treatment modality. There is minimal difference between 90-day mortality in patients treated with TORS or radiotherapy for early-stage OPSCC. While overall rates are low, for patients with expectation of cure, work is needed to identify optimal treatment.

Association of Inherited Copy Number Variation in ADAM3A and ADAM5 Pseudogenes with Oropharynx Cancer Risk and Outcome.

Inherited copy number variations (CNVs) can provide valuable information for cancer susceptibility and prognosis. However, their association with oropharynx squamous cell carcinoma (OPSCC) is still poorly studied. Using microarrays analysis, we identified three inherited CNVs associated with OPSCC risk, of which one was validated in 152 OPSCC patients and 155 controls and related to pseudogene-microRNA-mRNA interaction. Individuals with three or more copies of ADAM3A and ADAM5 pseudogenes (8p11.22 chromosome region) were under 6.49-fold increased risk of OPSCC. ADAM5 shared a highly homologous sequence with the ADAM9 3'-UTR, predicted to be a binding site for miR-122b-5p. Individuals carrying more than three copies of ADAM3A and ADAM5 presented higher ADAM9 expression levels. Moreover, patients with total deletion or one copy of pseudogenes and with higher expression of miR-122b-5p presented worse prognoses. Our data suggest, for the first time, that ADAM3A and ADAM5 pseudogene-inherited CNV could modulate OPSCC occurrence and prognosis, possibly through the interaction of ADAM5 pseudogene transcript, miR-122b-5p, and ADAM9.

Dynamic changes of hematological indices in oropharyngeal cancer patients treated with radiotherapy

Background Hematological indices assist in predicting clinical outcomes. Objectives To explore changes of hematological indices on oropharynx squamous cell carcinoma (OPSCC) patients received radiotherapy and their association with survival. Material and methods The white blood cell count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), hemoglobin (Hb), platelet (Plt), albumin (Alb), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline, 1-, 3-, 6- and 12-months follow-up were retrospectively collected. The trajectory of indices was described. A linear model with random effects was to describe indices’ changing rate and trend. Univariable Cox analysis was to assess the correlation between indices and survival. Results Of the 85 patients, WBC and ALC dropped during acute phase and gradually recovered, while NLR and PLR increased during acute phase and subsequently declined (all p < .01). Higher absolute value of nutritional indices (Alb and Hb) was associated with better prognosis (p < .05). In contrast, patients with higher absolute value or upward trend of inflammatory indices (ANC, Plt, NLR and PLR) had worse survival (p < .05). Conclusions and significance The short- and long-term changes of indices differed in OPSCC patients received radiotherapy, and absolute values and dynamic changes of indices had the potential to be prognostic factors.

Accuracy of response assessment FDG PET-CT post-(chemo)radiotherapy in HPV-negative oropharynx squamous cell carcinoma

Accuracy of response assessment FDG PET-CT post-(chemo)radiotherapy in HPV-negative oropharynx squamous cell carcinoma