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Cancer Feb 2022Transoral robotic surgery (TORS) was approved by the Food and Drug Administration in 2009 for the treatment of oropharyngeal cancers (oropharyngeal squamous cell...
BACKGROUND
Transoral robotic surgery (TORS) was approved by the Food and Drug Administration in 2009 for the treatment of oropharyngeal cancers (oropharyngeal squamous cell carcinoma [OPSCC]). This study investigated the adoption and safety of TORS.
METHODS
All patients who underwent TORS for OPSCC in the National Cancer Data Base from 2010 to 2016 were selected. Trends in the positive margin rate (PMR), 30-day unplanned readmission, and early postoperative mortality were evaluated. Outcomes after TORS, nonrobotic surgery (NRS), and nonsurgical treatment were compared with matched-pair survival analyses.
RESULTS
From 2010 to 2016, among 73,661 patients with OPSCC, 50,643 were treated nonsurgically, 18,024 were treated with NRS, and 4994 were treated with TORS. TORS utilization increased every year from 2010 (n = 363; 4.2%) to 2016 (n = 994; 8.3%). The TORS PMR for base of tongue malignancies decreased significantly over the study period (21.6% in 2010-2011 vs 15.8% in 2015-2016; P = .03). The TORS PMR at high-volume centers (≥10 cases per year; 11.2%) was almost half that of low-volume centers (<10 cases per year; 19.3%; P < .001). The rates of 30-day unplanned readmission (4.1%) and 30-day postoperative mortality (1.0%) after TORS were low and did not vary over time. High-volume TORS centers had significantly lower rates of 30-day postoperative mortality than low-volume centers (0.5% vs 1.5%; P = .006). In matched-pair analyses controlling for clinicopathologic cofactors, 30-, 60-, and 90-day posttreatment mortality did not vary among patients with OPSCC treated with TORS, NRS, or nonsurgical treatment.
CONCLUSIONS
TORS has become widely adopted and remains safe across the country with a very low risk of severe complications comparable to the risk with NRS. Although safety is excellent nationally, high-volume TORS centers have superior outcomes with lower rates of positive margins and early postoperative mortality.
Topics: Humans; Oropharyngeal Neoplasms; Retrospective Studies; Robotic Surgical Procedures; Squamous Cell Carcinoma of Head and Neck; Treatment Outcome
PubMed: 34762303
DOI: 10.1002/cncr.33995 -
Current Treatment Options in Oncology Jun 2021The rise in the incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPC), the relatively young age at which it is diagnosed, and... (Review)
Review
The rise in the incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPC), the relatively young age at which it is diagnosed, and its favorable prognosis necessitate the use of treatment techniques that reduce the likelihood of side effects during and after curative treatment. Intensity-modulated proton therapy (IMPT) is a form of radiotherapy that de-intensifies treatment through dose de-escalation to normal tissues without compromising dose to the primary tumor and involved, regional lymph nodes. Preclinical studies have demonstrated that HPV-positive squamous cell carcinoma is more sensitive to proton radiation than is HPV-negative squamous cell carcinoma. Retrospective studies comparing intensity-modulated photon (X-ray) radiotherapy to IMPT for OPC suggest comparable rates of disease control and lower rates of pain, xerostomia, dysphagia, dysgeusia, gastrostomy tube dependence, and osteoradionecrosis with IMPT-all of which meaningfully affect the quality of life of patients treated for HPV-associated OPC. Two phase III trials currently underway-the "Randomized Trial of IMPT versus IMRT for the Treatment of Oropharyngeal Cancer of the Head and Neck" and the "TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer (TORPEdO)" trial-are expected to provide prospective, level I evidence regarding the effectiveness of IMPT for such patients.
Topics: Alphapapillomavirus; Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Proton Therapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Randomized Controlled Trials as Topic; Squamous Cell Carcinoma of Head and Neck
PubMed: 34086150
DOI: 10.1007/s11864-021-00847-y -
BMC Public Health Jul 2021Oropharyngeal squamous cell carcinoma (OPSCC) is associated with high mortality. Human papillomavirus (HPV) infection is a significant risk factor for OPSCC. Utilities...
BACKGROUND
Oropharyngeal squamous cell carcinoma (OPSCC) is associated with high mortality. Human papillomavirus (HPV) infection is a significant risk factor for OPSCC. Utilities are fundamental values representing the strength of individuals' preferences for specific health-related outcomes. Our study aim was to work in partnership with Indigenous communities in South Australia to develop, pilot test and estimate utility scores for health states related to HPV, HPV vaccination, precursor OPSCC and its treatment, and early stage OPSCC among Indigenous Australians.
METHODS
Development and pilot testing of hypothetical HPV and OPSCC health states, specifically through the lens of being Indigenous Australian, was conducted with an Indigenous Reference Group. Six health states were decided upon, with utility scores calculated using a two-stage standard gamble approach among a large convenience sample of Indigenous Australians aged 18+ years residing in South Australia. The rank, percentage of perfect health and utility score of each health state was summarised using means, and medians at 12 months and lifetime duration. Potential differences by age, sex and residential location were assessed using the Wilcox Rank Sum test.
RESULTS
Data from 1011 participants was obtained. The mean utility scores decreased with increasing severity of health states, ranging from 0.91-0.92 in 'screened, cytology normal, HPV vaccination' and 'screened, HPV positive, endoscopy normal', to less than 0.90 (ranging from 0.87-0.88) in lower grade conditions (oral warts and oral intraepithelial neoplasia) and less than 0.80 (ranging from 0.75-0.79) in 'early stage throat cancer'. Higher utility scores were observed for 'screened, cytology normal and HPV vaccination' among younger participants (18-40 years), for 'early stage invasive throat cancer' among females, and for 'oral intraepithelial neoplasia' and 'early stage invasive throat cancer' among metropolitan-dwelling participants.
CONCLUSION
Among a large sample of Indigenous Australians, utility for oral HPV infection and OPSCC decreased with severity of health states. Older participants, as well as males and those residing in non-metropolitan locations, had decreased utility for high-grade cytology and early invasive cancer states. Our findings are an important contribution to cost-utility and disease prevention strategies that seek to inform policies around reducing HPV infection and OPSCC among all Australians.
Topics: Australia; Female; Head and Neck Neoplasms; Humans; Male; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; South Australia; Squamous Cell Carcinoma of Head and Neck
PubMed: 34311730
DOI: 10.1186/s12889-021-11496-z -
International Journal of Molecular... May 2020The oropharynx has become the leading primary site for Human Papilloma Virus (HPV)-associated head and neck cancer. HPV positive oropharyngeal squamous cell carcinoma... (Review)
Review
The oropharynx has become the leading primary site for Human Papilloma Virus (HPV)-associated head and neck cancer. HPV positive oropharyngeal squamous cell carcinoma (HPV+ OSCC) has emerged as an epidemic not easily recognized by many physicians, resulting in delays in diagnosis and management. HPV+ OSCC traditionally refers to younger, healthier patients with high economic status and high-risk sexual behavior and is related to improved prognosis. De-intensification strategies are being evaluated in ongoing clinical trials and if validated, might help spare severe morbidity associated with current cisplatin-based chemoradiotherapy, which is the standard of care for all patients with locally advanced head and neck cancer. On the other hand, whether HPV status represents an important prognostic factor for non-oropharyngeal sites remains to be elucidated.
Topics: Alphapapillomavirus; Carcinoma, Squamous Cell; Chemoradiotherapy; Head and Neck Neoplasms; Humans; Neoplasm Staging; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis; Survival Analysis
PubMed: 32403287
DOI: 10.3390/ijms21093388 -
Cancer Research Feb 2023Increasing rates of human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) have largely offset declines in tobacco-associated head and neck squamous cell carcinoma...
UNLABELLED
Increasing rates of human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) have largely offset declines in tobacco-associated head and neck squamous cell carcinoma (HNSCC) at non-OPC sites. Host immunity is an important modulator of HPV infection, persistence, and clearance, and also of immune evasion in both virally- and nonvirally-driven cancers. However, the association between collective known cancer-related immune gene variants and HNSCC susceptibility has not been fully characterized. Here, we conducted a genetic association study in the multiethnic Veterans Affairs Million Veteran Program cohort, evaluating 16,050 variants in 1,576 immune genes in 4,012 HNSCC cases (OPC = 1,823; non-OPC = 2,189) and 16,048 matched controls. Significant polymorphisms were further examined in a non-Hispanic white (NHW) validation cohort (OPC = 1,206; non-OPC = 955; controls = 4,507). For overall HNSCC susceptibility in NHWs, we discovered and validated a novel 9q31.1 SMC2 association and replicated the known 6p21.32 HLA-DQ-DR association. Six loci/genes for overall HNSCC susceptibility were selectively enriched in African-Americans (6p21.32 HLA-G, 9q21.33 GAS1, 11q12.2 CD6, 11q23.2 NCAM1/CD56, 17p13.1 CD68, 18q22.2 SOCS6); all 6 genes function in antigen-presenting regulation and T-cell activation. Two additional loci (10q26 DMBT1, 15q22.2 TPM1) were uncovered for non-OPC susceptibility, and three loci (11q24 CRTAM, 16q21 CDH5, 18q12.1 CDH2) were identified for HPV-positive OPC susceptibility. This study underscores the role of immune gene variants in modulating susceptibility for both HPV-driven and non-HPV-driven HNSCC. Additional large studies, particularly in racially diverse populations, are needed to further validate the associations and to help elucidate other potential immune factors and mechanisms that may underlie HNSCC risk.
SIGNIFICANCE
Several inherited variations in immune system genes are significantly associated with susceptibility to head and neck cancer, which could help improve personalized cancer risk estimates.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Veterans; Immunogenetics; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Oropharyngeal Neoplasms; Papillomavirus Infections; Human Papillomavirus Viruses; Calcium-Binding Proteins; DNA-Binding Proteins; Tumor Suppressor Proteins; Suppressor of Cytokine Signaling Proteins
PubMed: 36378845
DOI: 10.1158/0008-5472.CAN-22-1641 -
European Journal of Cancer (Oxford,... Aug 2022Our objective was to develop a predictive model using a machine learning signature to identify patients at high risk of relapse or death after treatment for HPV-positive...
OBJECTIVES
Our objective was to develop a predictive model using a machine learning signature to identify patients at high risk of relapse or death after treatment for HPV-positive oropharyngeal carcinoma.
MATERIALS AND METHODS
Pre-treatment variables of 450 patients with HPV-positive oropharyngeal carcinoma treated with a curative intent comprised clinical items, imaging parameters and histological findings. The events considered were progression or residual disease after treatment, the recurrent disease after a disease-free interval and death. The endpoints were the prediction of events and progression-free survival. After feature Z-score normalisation and selection, random forest classifier models were trained. The best models were evaluated on recall, the F-score, and the ROC AUC metric. The clinical relevance of the best prediction model was evaluated using Kaplan-Meier analysis with a log-rank test.
RESULTS
The best random forest model predicted the 5-year risk of relapse-free survival with a recall of 79.1%, an F1-score of 81.08%, and an AUC of the ROC curve of 0.89. The models performed poorly for the prediction of specific events of progression only, recurrence only or death only. The clinical relevance of the model was validated with a 5-year relapse-free survival of high-risk patients versus low-risk patients of 23.5% and 80%, respectively (p < 0.0001).
CONCLUSION
Patients with HPV-driven oropharyngeal carcinoma at high risk of relapse-free survival could be identified with a predictive machine learning model using patient data before treatment.
Topics: Carcinoma; Humans; Machine Learning; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis; Retrospective Studies
PubMed: 35714450
DOI: 10.1016/j.ejca.2022.05.003 -
BMC Oral Health Jun 2024Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and...
BACKGROUND
Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before.
METHODS
A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression.
RESULTS
Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267-0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036-7.825, p = 0.043).
CONCLUSIONS
We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC.
Topics: Humans; Oropharyngeal Neoplasms; Male; Female; Middle Aged; Prognosis; LIM Domain Proteins; Biomarkers, Tumor; Carcinoma, Squamous Cell; Aged; Transcription Factors; Membrane Glycoproteins; Adult; Ki-67 Antigen; Hyaluronan Receptors; Tumor Suppressor Protein p53; Papillomavirus Infections; Immunohistochemistry; Aged, 80 and over; Survival Rate
PubMed: 38918827
DOI: 10.1186/s12903-024-04510-4 -
Cancer Prevention Research... Aug 2020Head and neck squamous cell carcinoma (HNSCC) was the 7th most common malignancy worldwide in 2018 and despite therapeutic advances, the overall survival rate for oral... (Review)
Review
Head and neck squamous cell carcinoma (HNSCC) was the 7th most common malignancy worldwide in 2018 and despite therapeutic advances, the overall survival rate for oral squamous cell carcinoma (OSCC; ∼50%) has remained unchanged for decades. The most common types are OSCC and oropharyngeal squamous cell carcinoma (OPSCC, survival rate ∼85%). Tobacco smoking is a major risk factor of HNSCC. In the developed world, the incidence of OSCC is declining as a result of tobacco cessation programs. However, OPSCC, which is also linked to human papillomavirus (HPV) infection, is on the rise and now ranks as the most common HPV-related cancer. The current state of knowledge indicates that HPV-associated disease differs substantially from other types of HNSCC and distinct biological differences between HPV-positive and HPV-negative HNSCC have been identified. Although risk factors have been extensively discussed in the literature, there are multiple clinically relevant questions that remain unanswered and even unexplored. Moreover, existing approaches (e.g., tobacco cessation, vaccination, and chemoprevention) to manage and control this disease remain a challenge. Thus, in this review, we discuss potential future basic research that can assist in a better understanding of disease pathogenesis which may lead to novel and more effective preventive strategies for OSCC and OPSCC.
Topics: Alphapapillomavirus; Animals; Disease Models, Animal; Humans; Incidence; Mass Vaccination; Mice; Microbiota; Mouth; Mouth Neoplasms; Oropharyngeal Neoplasms; Papillomavirus Infections; Papillomavirus Vaccines; Risk Factors; Squamous Cell Carcinoma of Head and Neck; Tobacco Smoking; Tobacco Use Cessation
PubMed: 32434808
DOI: 10.1158/1940-6207.CAPR-20-0096 -
Association Between Up-front Surgery and Risk of Stroke in US Veterans With Oropharyngeal Carcinoma.JAMA Otolaryngology-- Head & Neck... Aug 2022Cardiovascular events are an important cause of morbidity in patients with oropharyngeal squamous cell carcinoma (OPSCC). Radiation and chemotherapy have been associated...
IMPORTANCE
Cardiovascular events are an important cause of morbidity in patients with oropharyngeal squamous cell carcinoma (OPSCC). Radiation and chemotherapy have been associated with increased risk of stroke; up-front surgery allows the opportunity for (chemo)radiotherapy de-escalation.
OBJECTIVE
To evaluate whether up-front surgery was associated with decreased stroke risk compared to nonsurgical treatment for OPSCC.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study was conducted at the US Veterans Health Administration and examined US veterans diagnosed with nonmetastatic OPSCC from 2000 to 2020. Data cutoff was September 17, 2021, and data analysis was performed from October 2021 to February 2022.
EXPOSURES
Up-front surgical treatment or definitive (chemo)radiotherapy as captured in cancer registry.
MAIN OUTCOMES AND MEASURES
Cumulative incidence of stroke, accounting for death as a competing risk; and association between up-front surgery and stroke risk. After generating propensity scores for the probability of receiving surgical treatment and using inverse probability weighting (IPW) to construct balanced pseudo-populations, Cox regression was used to estimate a cause-specific hazard ratio (csHR) of stroke associated with surgical vs nonsurgical treatment.
RESULTS
Of 10 436 patients, median (IQR) age was 61 (56-67) years; 10 329 (99%) were male; 1319 (13%) were Black, and 7823 (75%) were White; 2717 received up-front surgery, and 7719 received nonsurgical therapy with definitive (chemo)radiotherapy. The 10-year cumulative incidence of stroke was 12.5% (95% CI, 11.8%-13.3%) and death was 57.3% (95% CI, 56.2%-58.4%). Surgical patients who also received (chemo)radiotherapy had shorter radiation and chemotherapy courses than nonsurgical patients. After propensity score and IPW, the csHR of stroke for surgical treatment was 0.77 (95% CI, 0.66-0.91). This association was consistent across subgroups defined by age and baseline cardiovascular risk factors.
CONCLUSIONS AND RELEVANCE
In this cohort study, up-front surgical treatment was associated with a 23% reduced risk of stroke compared with definitive (chemo)radiotherapy. These findings present an important additional risk-benefit consideration to factor into treatment decisions and patient counseling and should motivate future studies to examine cardiovascular events in this high-risk population.
Topics: Aged; Carcinoma, Squamous Cell; Cardiovascular Diseases; Cohort Studies; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Oropharyngeal Neoplasms; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Stroke; Veterans
PubMed: 35737359
DOI: 10.1001/jamaoto.2022.1327 -
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