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EBioMedicine Dec 2022There is significant interest in treatment de-escalation for human papillomavirus-associated (HPV) oropharyngeal squamous cell carcinoma (OPSCC) patients given the...
BACKGROUND
There is significant interest in treatment de-escalation for human papillomavirus-associated (HPV) oropharyngeal squamous cell carcinoma (OPSCC) patients given the generally favourable prognosis. However, 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to risk stratify HPV OPSCC patients.
METHODS
We created an immune score (UWO3) associated with survival outcomes in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes.
FINDINGS
A three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival compared to the immune desert (HR = 9.0, 95% CI: 3.2-25.5, P = 3.6 × 10) and mixed (HR = 6.4, 95% CI: 2.2-18.7, P = 0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two small treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation.
INTERPRETATION
With additional prospective validation, the UWO3 score could enable biomarker-driven clinical decision-making for patients with HPV OPSCC based on robust outcome prediction across six independent cohorts. Prospective de-escalation and intensification clinical trials are currently being planned.
FUNDING
CIHR, European Union, and the NIH.
Topics: Humans; Papillomavirus Infections; Retrospective Studies; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Prognosis; Biomarkers; Human Papillomavirus Viruses; Head and Neck Neoplasms; Papillomaviridae
PubMed: 36442320
DOI: 10.1016/j.ebiom.2022.104373 -
Laryngo- Rhino- Otologie May 2022Robotic systems for head and neck surgery are at different stages of technical development and clinical application. Currently, robotic systems are predominantly used... (Review)
Review
Robotic systems for head and neck surgery are at different stages of technical development and clinical application. Currently, robotic systems are predominantly used for transoral surgery of the pharynx and larynx. Robotic surgery of the neck, the thyroid, and the middle and inner ear is much less common; however, some oncological and functional outcomes have been reported. This article provides an overview of the current state of robot-assisted head and neck surgery with a special emphasis on patient benefit and postoperative quality of life (QoL). The focus is placed on the role of transoral robotic surgery (TORS) for the resection of oropharyngeal carcinomas. For this application, reported long-term outcomes show functional post-operative advantages for selected oropharyngeal cancer patients after TORS compared to open surgery and primary radiotherapy. Since TORS also plays a significant role in the context of potential therapy de-escalation for HPV-positive oropharyngeal cancer patients, ongoing trials are presented. Regarding the evaluation of the therapeutic benefit and the QoL of cancer patients, special attention has to be paid to the large degree of variability of individual patients' preferences. Influencing factors and tools for a detailed assessment of QoL parameters are therefore detailed at the beginning of this article. Notably, while some robotic systems for ear and skull base surgery are being developed in Europe, TORS systems are mainly used in North America and Asia. In Europe and Germany in particular, transoral laser microsurgery (TLM) is a well-established technology for transoral tumor resection. Future trials comparing TORS and TLM with detailed investigation of QoL parameters are therefore warranted and might contribute to identifying suitable fields for the application of the different techniques.
Topics: Humans; Microsurgery; Oropharyngeal Neoplasms; Quality of Life; Robotic Surgical Procedures; Robotics; Treatment Outcome
PubMed: 35605618
DOI: 10.1055/a-1647-8650 -
Bone Marrow Transplantation Jan 2022We analyzed subsequent cancers in 329 patients with aplastic anemia given HLA-matched related marrow grafts. Median follow-up: 26 (range 1-47) years. Conditioning:...
We analyzed subsequent cancers in 329 patients with aplastic anemia given HLA-matched related marrow grafts. Median follow-up: 26 (range 1-47) years. Conditioning: cyclophosphamide ± antithymocyte globulin; graft-vs.-host disease (GVHD) prevention: methotrexate ± cyclosporine. The long follow-up and homogeneous treatment allowed definitive analyses of incidence, nature, time of onset, and potential causes of cancers. Fifty-three cancers occurred in 46 patients, 42 had solid tumors and 4 blood cancers. Of the 42, 22 had non-melanoma skin and 7 oropharyngeal cancers. The remainder had a spectrum of other cancers including two liver cancers from pre-transplant hepatitis C. The 26-year cumulative incidence (CI) of cancer was 11% and mortality 5%. Excluding non-melanoma skin cancers, the 26-year CI of cancer was 7%. Cancers were 2.03-fold more than expected from SEER data; that number was 1.89-fold after excluding liver cancers. Nearly all cancers developed between 14 and 34 years. Skin and oropharyngeal cancers showed significant association with chronic GVHD, whereby GVHD had resolved in most patients within 7 years of transplantation. Thus, tumors evolved after a lag time of 7-27 years. Other cancers showed no clear associations with chronic GVHD or drugs used for transplantation. Results reemphasize the importance of preventing chronic GVHD.
Topics: Anemia, Aplastic; Bone Marrow Transplantation; Cyclophosphamide; Graft vs Host Disease; Humans; Liver Neoplasms; Oropharyngeal Neoplasms; Transplantation Conditioning
PubMed: 34657145
DOI: 10.1038/s41409-021-01498-1 -
Ear, Nose, & Throat Journal Aug 2021Incidental papillomas of the pharynx can be found while examining the nasopharynx, oropharynx, and hypopharynx for other disorders of the head and neck. Purpose of the...
INTRODUCTION
Incidental papillomas of the pharynx can be found while examining the nasopharynx, oropharynx, and hypopharynx for other disorders of the head and neck. Purpose of the study is to explore the location, biopsy protocol, and decision to perform office-based versus operative management via potassium titanyl phosphate (KTP) laser when an oropharyngeal papilloma is discovered incidentally.
METHODS
A retrospective review of the senior author's patient population was performed using Current Procedural Terminology and/or codes to identify patients who had KTP laser removal of incidental oropharyngeal papillomas. Patients were included based on the incidental nature of the papilloma and confirmed pathology report of squamous papilloma. Demographics, presenting complaint, lesion location, pathological analysis, type of intervention, and outcomes were recorded. When available, human papillomavirus (HPV) subtype was noted.
RESULTS
A total of 26 cases were identified, 13 females and 13 males. The median age at time of surgery was 58 years (range: 21-77). The most common presenting symptoms were difficulty swallowing and throat pain. The most common locations were the base of tongue, uvula, tonsils, and the soft palate. Of the 26 patients, 23 patients received KTP laser ablation therapy as an office-based procedure, while the remaining 3 were performed under general anesthesia in the operating room. Only 5 patients had a recorded recurrence that required reoperation. There were no operative or postoperative complications. There were 16 biopsy samples tested for HPV, where 12 were negative for HPV and 4 were positive for HPV.
CONCLUSION
Oropharyngeal papillomas, when present, can be found incidentally during examination of the oropharynx for other symptoms. Office-based biopsy and KTP laser is a safe and efficient means of identifying and removing most oropharyngeal papillomas.
Topics: Adult; Aged; Ambulatory Surgical Procedures; Biopsy; Clinical Decision-Making; Deglutition Disorders; Female; Humans; Incidental Findings; Lasers, Solid-State; Male; Middle Aged; Oropharyngeal Neoplasms; Oropharynx; Papilloma; Retrospective Studies; Young Adult
PubMed: 31581834
DOI: 10.1177/0145561319871228 -
TheScientificWorldJournal 2021Oral and oropharyngeal cancer is a debilitating disease with high morbidity and mortality. Depending on the site and extent of the involvement of the cancer and the type...
BACKGROUND
Oral and oropharyngeal cancer is a debilitating disease with high morbidity and mortality. Depending on the site and extent of the involvement of the cancer and the type of treatment modality, these patients can develop pain, trismus, xerostomia, dysphagia, and taste disturbances, compromising them socially and nutritionally. The aim of the study was to evaluate malnutrition and quality of life in patients treated for oral and oropharyngeal cancer. . A cross-sectional study was conducted which included 97 patients treated for oral and oropharyngeal cancer. The quality of life of the selected patients was assessed by using a validated European Organization for the Research and Treatment of Cancer's Quality of Life Questionnaire, Head and Neck and Mandibular Function Impairment Questionnaire. Pre- and posttreatment weight of the patients were assessed, and weight loss of ≥10% of pretreatment weight was considered as malnutrition. The chi-square test was used to correlate the symptoms with the quality of life. A paired test was used to assess the differences in weight before and after treatment, and a value of <0.005 was considered as significant.
RESULTS
The most commonly reported symptoms were xerostomia (93.81%), pain (81.44%), and dysphagia (76.3%). A total of 40.2% of the individuals in the study had malnutrition. Malnutrition was comparatively lower in the group who had nutritional supplements.
CONCLUSION
The quality of life in patients treated for oral and oropharyngeal cancer deteriorates immediately after the treatment; however, it significantly improves over time.
Topics: Cross-Sectional Studies; Deglutition Disorders; Female; Humans; Male; Malnutrition; Middle Aged; Mouth Neoplasms; Oropharyngeal Neoplasms; Quality of Life; Surveys and Questionnaires; Xerostomia
PubMed: 34381320
DOI: 10.1155/2021/9936715 -
Cancer May 2021Modern disease staging systems have restructured human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) oropharyngeal carcinoma (OPC) into distinct...
BACKGROUND
Modern disease staging systems have restructured human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) oropharyngeal carcinoma (OPC) into distinct pathologic nodal systems. Given that quantitative lymph node (LN) burden is the dominant prognostic factor in most head and neck cancers, we investigated whether HPV- and HPV+ OPC warrant divergent pathologic nodal classification.
METHODS
Multivariable Cox regression models of OPC surgical patients identified via U.S. cancer registry data were constructed to determine associations between survival and nodal characteristics. Nonlinear associations between metastatic LN number and survival were modeled with restricted cubic splines. Recursive partitioning analysis (RPA) was used to derive unbiased nodal schema.
RESULTS
Mortality risk escalated continuously with each successive positive LN in both OPC subtypes, with analogous slope. Survival hazard increased by 18.5% (hazard ratio [HR], 1.19 [95% CI, 1.16-1.21]; P < .001) and 19.1% (HR, 1.19 [95% CI, 1.17-1.21]; P < .001), with each added positive LN for HPV- and HPV+ OPC, respectively, up to identical change points of 5 positive LNs. Extranodal extension (ENE) was an independent predictor of HPV- OPC (HR, 1.55 [95% CI, 1.20-1.99]; P < .001) and HPV+ OPC (HR 1.73 [95% CI, 1.36-2.20]; P < .001) mortality. In RPA for both diseases, metastatic LN was the principal nodal covariate driving survival, with ENE as a secondary determinant. Given the similarities across analyses, we propose a concise, unifying HPV-/HPV+ OPC pathologic nodal classification schema: N1, 1-5 LN+/ENE-; N2, 1-5 LN+/ENE+; N3, >5 LN+.
CONCLUSION
HPV- and HPV+ OPC exhibit parallel relationships between nodal characteristics and relative mortality. In both diseases, metastatic LN number represents the principal nodal covariate governing survival, with ENE being an influential secondary element. A consolidated OPC pathologic nodal staging system that is based on these covariates may best convey prognosis.
LAY SUMMARY
The current nodal staging system for oropharyngeal carcinoma (OPC) has divided human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) OPC into distinct systems that rely upon criteria that establish them as separate entities, a complexity that may undermine the core objective of staging schema to clearly communicate prognosis. Our large-scale analysis revealed that HPV- and HPV+ pathologic nodal staging systems in fact mirror each other. Multiple analyses produced conspicuously similar nodal staging systems, with metastatic lymph node number and extranodal extension delineating the highest risk groups that shape prognosis. We propose unifying HPV- and HPV+ nodal systems to best streamline prognostication and maximize staging accuracy.
Topics: Carcinoma; Humans; Neoplasm Staging; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis
PubMed: 33595897
DOI: 10.1002/cncr.33414 -
Journal of Zhejiang University....Worldwide there has been a significant increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) etiologically attributed to oncogenic human... (Review)
Review
Worldwide there has been a significant increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) etiologically attributed to oncogenic human papillomavirus (HPV). Reliable and accurate identification and detection tools are important as the incidence of HPV-related cancer is on the rise. Several HPV detection methods for OPSCC have been developed and each has its own advantages and disadvantages in regard to sensitivity, specificity, and technical difficulty. This review summarizes our current knowledge of molecular methods for detecting HPV in OPSCC, including HPV DNA/RNA polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), p16 immunohistochemistry (IHC), and DNA/RNA in situ hybridization (ISH) assays. This summary may facilitate the selection of a suitable method for detecting HPV infection, and therefore may help in the early diagnosis of HPV-related carcinoma to reduce its mortality, incidence, and morbidity.
Topics: Alphapapillomavirus; Cyclin-Dependent Kinase Inhibitor p16; Immunohistochemistry; In Situ Hybridization; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Oropharyngeal Neoplasms; Polymerase Chain Reaction; Squamous Cell Carcinoma of Head and Neck
PubMed: 33843162
DOI: 10.1631/jzus.B2000161 -
Cell Reports. Medicine Nov 2023Tumor-infiltrating HPV16-E2-specific CD8 T cells have been detected in HPV16-induced oropharyngeal squamous cell carcinoma (OPSCC). Whether intratumoral CD4 T cells...
Tumor-infiltrating HPV16-E2-specific CD8 T cells have been detected in HPV16-induced oropharyngeal squamous cell carcinoma (OPSCC). Whether intratumoral CD4 T cells target HPV16 E2 and if HPV16-E2-specific immunity contributes to better clinical outcome is unknown. In a prospective HPV16 OPSCC cohort, we regularly detect HPV16-E2-specific CD4 and CD8 intratumoral T cells, albeit at lower frequencies than the co-infiltrating HPV16-E6/E7-specific T cells. These HPV16-reactive T cells produce multiple cytokines when activated, indicating their polyfunctionality. Importantly, their combined intratumoral presence predicts superior survival, emphasizing the value of HPV16-E2-specific T cells in anti-tumor immunity and suggests its use as a target antigen for immunotherapy.
Topics: Humans; Human papillomavirus 16; CD8-Positive T-Lymphocytes; Prospective Studies; Papillomavirus Infections; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms
PubMed: 37924817
DOI: 10.1016/j.xcrm.2023.101262 -
Brazilian Oral Research 2023The aim of this study was to evaluate the time elapsed from first symptoms to the treatment of oral and oropharyngeal cancer (OOC) and to identify variables associated... (Observational Study)
Observational Study
The aim of this study was to evaluate the time elapsed from first symptoms to the treatment of oral and oropharyngeal cancer (OOC) and to identify variables associated with treatment delay. This is an observational study with retrospective and prospective data collection. Patients with a diagnosis of OOC seen at the Head and Neck Surgery outpatient clinic of a Brazilian public hospital were included and followed up to treatment initiation. Participants answered a questionnaire for the collection of socioeconomic, demographic, cultural, and clinical information, as well as information about the time elapsed from first symptoms to the first appointment with a head and neck surgeon. Time to treatment was classified into four intervals: 1- first symptoms to first medical appointment; 2- first medical appointment to specialized medical care; 3- specialized medical care to preparation for treatment; and 4- preparation for treatment to treatment initiation. Bivariate statistics were computed. Out of 100 participants, nine died before treatment. Mean time to treatment was 217 days. Highest mean time was observed for interval 2 (94 days), followed by interval 1 (63 days), interval 4 (39 days), and interval 3 (21 days). At interval 1, a longer time was associated with severe alcohol consumption, severe smoking, and family history of cancer. At interval 2, the delay was associated with appointment with a general practitioner, clinical diagnosis of disease other than cancer, and antibiotic prescription. At interval 4, delay in treatment was associated with surgical treatment. Patients with OOC experience delays from symptom onset to treatment initiation. The longest interval was associated with professional delay, followed by patient delay in help-seeking.
Topics: Humans; Retrospective Studies; Oropharyngeal Neoplasms; Patient Acceptance of Health Care; Smoking; Brazil
PubMed: 37255074
DOI: 10.1590/1807-3107bor-2023.vol37.0054 -
Clinical Cancer Research : An Official... Oct 2022Despite generally favorable outcomes, 15% to 25% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will have recurrence....
PURPOSE
Despite generally favorable outcomes, 15% to 25% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will have recurrence. Current posttreatment surveillance practices rely on physical examinations and imaging and are inconsistently applied. We assessed circulating tumor tissue modified viral (TTMV)-HPV DNA obtained during routine posttreatment surveillance among a large population of real-world patients.
EXPERIMENTAL DESIGN
This retrospective clinical case series included 1,076 consecutive patients across 108 U.S. sites who were ≥ 3 months posttreatment for HPV-driven OPSCC and who had one or more TTMV-HPV DNA tests (NavDx, Naveris Laboratories) obtained during surveillance between February 6, 2020, and June 29, 2021. Test results were compared with subsequent clinical evaluations.
RESULTS
Circulating TTMV-HPV DNA was positive in 80 of 1,076 (7.4%) patients, with follow-up available on all. At first positive surveillance testing, 21 of 80 (26%) patients had known recurrence while 59 of 80 (74%) patients were not known to have recurrent disease. Among these 59 patients, 55 (93%) subsequently had a confirmed recurrence, 2 patients had clinically suspicious lesions, and 2 had clinically "no evidence of disease" (NED) at last follow-up. To date, the overall positive predictive value of TTMV-HPV DNA testing for recurrent disease is 95% (N = 76/80). In addition, the point-in-time negative predictive value is 95% (N = 1,198/1,256).
CONCLUSIONS
These findings highlight the clinical potential for circulating TTMV-HPV DNA testing in routine practice. As a surveillance tool, TTMV-HPV DNA positivity was the first indication of recurrence in the majority of cases, pre-dating identification by routine clinical and imaging exams. These data may inform future clinical and guideline-endorsed strategies for HPV-driven malignancy surveillance. See related commentary by Colevas, p. 4171.
Topics: Alphapapillomavirus; Biomarkers; DNA, Viral; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck
PubMed: 35576437
DOI: 10.1158/1078-0432.CCR-22-0562