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Seminars in Radiation Oncology Oct 2021Human papillomavirus is the most common sexually transmitted infection in the world and had been linked to both anogenital and oropharyngeal cancers. It causes nearly... (Review)
Review
Human papillomavirus is the most common sexually transmitted infection in the world and had been linked to both anogenital and oropharyngeal cancers. It causes nearly 100% of cervical cancers and an increasing portion of oropharyngeal cancers. The geographical burden of cervical HPV infection and associated cancers is not uniform and is mainly found in low middle income countries in South America, Africa, and Asia. However, HPV-positive oropharyngeal cancer is rapidly becoming more prevalent in high middle income countries. With the development of vaccines which prevent HPV infection, the World Health Organization has designated the extirpation of HPV and its associated cancers a priority. Countries that have implemented adequate vaccine programs have shown a decrease in HPV prevalence. Understanding the epidemiology of HPV and its associated cancers is fundamental in improving vaccine programs and other health programs.
Topics: Female; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prevalence; Uterine Cervical Neoplasms
PubMed: 34455984
DOI: 10.1016/j.semradonc.2021.04.001 -
Nature Reviews. Clinical Oncology May 2022Human papillomavirus (HPV)-positive (HPV) oropharyngeal squamous cell carcinoma (OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income... (Review)
Review
Human papillomavirus (HPV)-positive (HPV) oropharyngeal squamous cell carcinoma (OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries. The most recent (8th) edition of the UICC/AJCC staging system separates HPV OPSCC from its HPV-negative (HPV) counterpart to account for the improved prognosis seen in the former. Indeed, owing to its improved prognosis and greater prevalence in younger individuals, numerous ongoing trials are examining the potential for treatment de-intensification as a means to improve quality of life while maintaining acceptable survival outcomes. In addition, owing to the distinct biology of HPV OPSCCs, targeted therapies and immunotherapies have become an area of particular interest. Importantly, OPSCC is often detected at an advanced stage owing to a lack of symptoms in the early stages; therefore, a need exists to identify and validate possible diagnostic biomarkers to aid in earlier detection. In this Review, we provide a summary of the epidemiology, molecular biology and clinical management of HPV OPSCC in an effort to highlight important advances in the field. Ultimately, a need exists for improved understanding of the molecular basis and clinical course of this disease to guide efforts towards early detection and precision care, and to improve patient outcomes.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Molecular Epidemiology; Oropharyngeal Neoplasms; Papillomavirus Infections; Quality of Life; Squamous Cell Carcinoma of Head and Neck
PubMed: 35105976
DOI: 10.1038/s41571-022-00603-7 -
Journal of Clinical Oncology : Official... Jan 2022Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a... (Randomized Controlled Trial)
Randomized Controlled Trial
Phase II Randomized Trial of Transoral Surgery and Low-Dose Intensity Modulated Radiation Therapy in Resectable p16+ Locally Advanced Oropharynx Cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311).
PURPOSE
Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC.
METHODS
E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index.
RESULTS
Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6]) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented.
CONCLUSION
Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Chemoradiotherapy, Adjuvant; Cisplatin; Cyclin-Dependent Kinase Inhibitor p16; Feasibility Studies; Female; Humans; Male; Middle Aged; Oropharyngeal Neoplasms; Papillomaviridae; Pharyngectomy; Progression-Free Survival; Prospective Studies; Radiotherapy, Intensity-Modulated; Squamous Cell Carcinoma of Head and Neck; Time Factors
PubMed: 34699271
DOI: 10.1200/JCO.21.01752 -
Clinical & Translational Oncology :... May 2021Head and neck cancers (HNC) are defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than...
Head and neck cancers (HNC) are defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2017 publication, the Spanish Society of Medical Oncology (SEOM) presents an update of the squamous cell HNC diagnosis and treatment guideline. Most relevant diagnostic and therapeutic changes from the last guideline have been updated: introduction of sentinel node biopsy in early oral/oropharyngeal cancer treated with surgery, concomitant radiotherapy with weekly cisplatin 40 mg/m in the adjuvant setting, new approaches for HPV-related oropharyngeal cancer and new treatments with immune-checkpoint inhibitors in recurrent/metastatic disease.
Topics: Alphapapillomavirus; Chemoradiotherapy, Adjuvant; Cisplatin; Head and Neck Neoplasms; Humans; Immune Checkpoint Inhibitors; Medical Oncology; Mouth Neoplasms; Neoplasm Staging; Organ Sparing Treatments; Oropharyngeal Neoplasms; Radiation-Sensitizing Agents; Radiotherapy, Adjuvant; Sentinel Lymph Node Biopsy; Societies, Medical; Spain; Squamous Cell Carcinoma of Head and Neck
PubMed: 33635468
DOI: 10.1007/s12094-020-02533-1 -
Annual Review of Pathology Jan 2023Human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries.... (Review)
Review
Human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries. The most recent (8th) edition of the Union for International Cancer Control/American Joint Committee on Cancer staging system separates HPV-OPSCC from its HPV-negative counterpart to account for the improved prognosis seen in the former. Indeed, owing to its improved prognosis and greater prevalence in younger individuals, numerous ongoing trials are examining the potential for treatment deintensification as a means to improve quality of life while maintaining acceptable survival outcomes. Owing to the distinct biology of HPV-OPSCCs, targeted therapies and immunotherapies have become an area of particular interest. Importantly, OPSCC is often detected at an advanced stage, highlighting the need for diagnostic biomarkers to aid in earlier detection. In this review, we highlight important advances in the epidemiology, pathology, diagnosis, and clinical management of HPV-OPSCC and underscore the need for a progressive understanding of the molecular basis of this disease toward early detection and precision care.
Topics: Humans; Papillomavirus Infections; Quality of Life; Oropharyngeal Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Prognosis; Head and Neck Neoplasms
PubMed: 36693202
DOI: 10.1146/annurev-pathmechdis-031521-041424 -
The Cochrane Database of Systematic... Dec 2021Oral cavity and oropharyngeal cancers are the most common cancers arising in the head and neck. Treatment of oral cavity cancer is generally surgery followed by... (Review)
Review
BACKGROUND
Oral cavity and oropharyngeal cancers are the most common cancers arising in the head and neck. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. This review updates one last published in 2011.
OBJECTIVES
To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal squamous cell carcinoma results in improved overall survival, improved disease-free survival and/or improved locoregional control, when incorporated as either induction therapy given prior to locoregional treatment (i.e. radiotherapy or surgery), concurrent with radiotherapy or in the adjuvant (i.e. after locoregional treatment with radiotherapy or surgery) setting.
SEARCH METHODS
An information specialist searched 4 bibliographic databases up to 15 September 2021 and used additional search methods to identify published, unpublished and ongoing studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and that evaluated the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration.
DATA COLLECTION AND ANALYSIS
For this update, we assessed the new included trials for their risk of bias and at least two authors extracted data from them. Our primary outcome was overall survival (time to death from any cause). Secondary outcomes were disease-free survival (time to disease recurrence or death from any cause) and locoregional control (response to primary treatment). We contacted trial authors for additional information or clarification when necessary.
MAIN RESULTS
We included 100 studies with 18,813 participants. None of the included trials were at low risk of bias. For induction chemotherapy, we reported the results for contemporary regimens that will be of interest to clinicians and people being treated for oral cavity and oropharyngeal cancers. Overall, there is insufficient evidence to clearly demonstrate a survival benefit from induction chemotherapy with platinum plus 5-fluorouracil prior to radiotherapy (hazard ratio (HR) for death 0.85, 95% confidence interval (CI) 0.70 to 1.04, P = 0.11; 7427 participants, 5 studies; moderate-certainty evidence), prior to surgery (HR for death 1.06, 95% CI 0.71 to 1.60, P = 0.77; 198 participants, 1 study; low-certainty evidence) or prior to concurrent chemoradiation (CRT) with cisplatin (HR for death 0.71, 95% CI 0.37 to 1.35, P = 0.30; 389 participants, 2 studies; low-certainty evidence). There is insufficient evidence to support the use of an induction chemotherapy regimen with cisplatin plus 5-fluorouracil plus docetaxel prior to CRT with cisplatin (HR for death 1.08, 95% CI 0.80 to 1.44, P = 0.63; 760 participants, 3 studies; low-certainty evidence). There is insufficient evidence to support the use of adjuvant chemotherapy over observation only following surgery (HR for death 0.95, 95% CI 0.73 to 1.22, P = 0.67; 353 participants, 5 studies; moderate-certainty evidence). Among studies that compared post-surgical adjuvant CRT, as compared to post-surgical RT, adjuvant CRT showed a survival benefit (HR 0.84, 95% CI 0.72 to 0.98, P = 0.03; 1097 participants, 4 studies; moderate-certainty evidence). Primary treatment with CRT, as compared to radiotherapy alone, was associated with a reduction in the risk of death (HR for death 0.74, 95% CI 0.67 to 0.83, P < 0.00001; 2852 participants, 24 studies; moderate-certainty evidence). AUTHORS' CONCLUSIONS: The results of this review demonstrate that chemotherapy in the curative-intent treatment of oral cavity and oropharyngeal cancers only seems to be of benefit when used in specific circumstances together with locoregional treatment. The evidence does not show a clear survival benefit from the use of induction chemotherapy prior to radiotherapy, surgery or CRT. Adjuvant CRT reduces the risk of death by 16%, as compared to radiotherapy alone. Concurrent chemoradiation as compared to radiation alone is associated with a greater than 20% improvement in overall survival; however, additional research is required to inform how the specific chemotherapy regimen may influence this benefit.
Topics: Chemoradiotherapy, Adjuvant; Humans; Mouth Neoplasms; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms
PubMed: 34929047
DOI: 10.1002/14651858.CD006386.pub4 -
JAMA Oncology Jun 2022The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown. (Randomized Controlled Trial)
Randomized Controlled Trial
Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.
IMPORTANCE
The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown.
OBJECTIVE
To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC.
DESIGN, SETTING, AND PARTICIPANTS
This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up.
INTERVENTIONS
Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings).
MAIN OUTCOMES AND MEASURES
The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects.
RESULTS
Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes.
TRIAL REGISTRATION
Clinicaltrials.gov Identifier: NCT03210103.
Topics: Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Oropharyngeal Neoplasms; Papillomavirus Infections; Quality of Life; Squamous Cell Carcinoma of Head and Neck
PubMed: 35482348
DOI: 10.1001/jamaoncol.2022.0615 -
Journal of Clinical Oncology : Official... Mar 2021Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus-associated oropharyngeal squamous cell... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven.
PATIENTS AND METHODS
In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI).
RESULTS
Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% ( = .04). For IMRT, 2-year PFS was 87.6% ( = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% 52.4%; < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% ( = .56).
CONCLUSION
The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.
Topics: Adult; Aged; Aged, 80 and over; Chemoradiotherapy; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Squamous Cell Carcinoma of Head and Neck; Survival Rate
PubMed: 33507809
DOI: 10.1200/JCO.20.03128 -
ELife Apr 2023A recent World Health Organization report states that at least 40% of all cancer cases may be preventable, with smoking, alcohol consumption, and obesity identified as...
A recent World Health Organization report states that at least 40% of all cancer cases may be preventable, with smoking, alcohol consumption, and obesity identified as three of the most important modifiable lifestyle factors. Given the significant decline in smoking rates, particularly within developed countries, other potentially modifiable risk factors for head and neck cancer warrant investigation. Obesity and related metabolic disorders such as type 2 diabetes (T2D) and hypertension have been associated with head and neck cancer risk in multiple observational studies. However, adiposity has also been correlated with smoking, with bias, confounding or reverse causality possibly explaining these findings. To overcome the challenges of observational studies, we conducted two-sample Mendelian randomization (inverse variance weighted [IVW] method) using genetic variants which were robustly associated with adiposity, glycaemic and blood pressure traits in genome-wide association studies (GWAS). Outcome data were taken from the largest available GWAS of 6034 oral and oropharyngeal cases, with 6585 controls. We found limited evidence of a causal effect of genetically proxied body mass index (BMI; OR IVW = 0.89, 95% CI 0.72-1.09, p = 0.26 per 1 standard deviation in BMI [4.81kg/m]) on oral and oropharyngeal cancer risk. Similarly, there was limited evidence for related traits including T2D and hypertension. Small effects cannot be excluded given the lack of power to detect them in currently available GWAS.
Topics: Humans; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Mendelian Randomization Analysis; Risk Factors; Oropharyngeal Neoplasms; Obesity; Hypertension; Polymorphism, Single Nucleotide
PubMed: 37042641
DOI: 10.7554/eLife.82674 -
JAMA Network Open Nov 2020Postoperative chemoradiation is the standard of care for cancers with positive margins or extracapsular extension, but the benefit of chemotherapy is unclear for...
IMPORTANCE
Postoperative chemoradiation is the standard of care for cancers with positive margins or extracapsular extension, but the benefit of chemotherapy is unclear for patients with other intermediate risk features.
OBJECTIVE
To evaluate whether machine learning models could identify patients with intermediate-risk head and neck squamous cell carcinoma who would benefit from chemoradiation.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included patients diagnosed with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx from January 1, 2004, through December 31, 2016. Patients had resected disease and underwent adjuvant radiotherapy. Analysis was performed from October 1, 2019, through September 1, 2020. Patients were selected from the National Cancer Database, a hospital-based registry that captures data from more than 70% of newly diagnosed cancers in the United States. Three machine learning survival models were trained using 80% of the cohort, with the remaining 20% used to assess model performance.
EXPOSURES
Receipt of adjuvant chemoradiation or radiation alone.
MAIN OUTCOMES AND MEASURES
Patients who received treatment recommended by machine learning models were compared with those who did not. Overall survival for treatment according to model recommendations was the primary outcome. Secondary outcomes included frequency of recommendation for chemotherapy and chemotherapy benefit in patients recommended for chemoradiation vs radiation alone.
RESULTS
A total of 33 527 patients (24 189 [72%] men; 28 036 [84%] aged ≤70 years) met the inclusion criteria. Median follow-up in the validation data set was 43.2 (interquartile range, 19.8-65.5) months. DeepSurv, neural multitask logistic regression, and survival forest models recommended chemoradiation for 17 589 (52%), 15 917 (47%), and 14 912 patients (44%), respectively. Treatment according to model recommendations was associated with a survival benefit, with a hazard ratio of 0.79 (95% CI, 0.72-0.85; P < .001) for DeepSurv, 0.83 (95% CI, 0.77-0.90; P < .001) for neural multitask logistic regression, and 0.90 (95% CI, 0.83-0.98; P = .01) for random survival forest models. No survival benefit for chemotherapy was seen for patients recommended to receive radiotherapy alone.
CONCLUSIONS AND RELEVANCE
These findings suggest that machine learning models may identify patients with intermediate risk who could benefit from chemoradiation. These models predicted that approximately half of such patients have no added benefit from chemotherapy.
Topics: Aged; Chemoradiotherapy, Adjuvant; Cohort Studies; Deep Learning; Female; Humans; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Logistic Models; Lymph Nodes; Machine Learning; Male; Mouth Neoplasms; Neoplasm Grading; Neoplasm Staging; Neural Networks, Computer; Oropharyngeal Neoplasms; Otorhinolaryngologic Surgical Procedures; Patient Selection; Proportional Hazards Models; Radiotherapy, Adjuvant; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Tumor Burden
PubMed: 33211108
DOI: 10.1001/jamanetworkopen.2020.25881