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International Journal of Clinical... Aug 2023Classical oropharyngeal squamous cell carcinoma (OPSCC) caused by alcohol consumption and smoking and HPV-associated OPSCC caused by human papillomavirus (HPV) infection... (Review)
Review
Classical oropharyngeal squamous cell carcinoma (OPSCC) caused by alcohol consumption and smoking and HPV-associated OPSCC caused by human papillomavirus (HPV) infection have different etiologies, incidences, and prognoses. Therefore, the 8th American Joint committee on Cancer (AJCC) and Union for International Cancer Control (UICC) TNM classifications propose distinguishing HPV-associated OPSCC from classical OPSCC and classifying it as an independent disease. Therefore, this review provides an overview of HPV-associated OPSCC from the perspectives of epidemiology, carcinogenesis, development, diagnosis, treatment, and prevention. The incidence of HPV-associated OPSCC is increasing. Although HPV vaccination has been shown to be effective at reducing the incidence of cervical cancer, it is still unclear how it affects the incidence of HPV-associated OPSCC. Additionally, the prognosis of patients with HPV-associated OPSCC is extremely favorable compared to that of patients with classical OPSCC. Therefore, patients with HPV-associated OPSCC may undergo reduced-dose therapy, although attempts to reduce treatment intensity should be carefully planned to ensure they do not compromise oncological outcomes, and large-scale trials aimed at reducing treatment intensity are ongoing.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Human Papillomavirus Viruses; Carcinoma, Squamous Cell; Oropharyngeal Neoplasms; Papillomavirus Infections; Papillomaviridae; Prognosis; Head and Neck Neoplasms
PubMed: 37093464
DOI: 10.1007/s10147-023-02336-8 -
Medicina (Kaunas, Lithuania) Aug 2022to show an overview on the treatments' options for stage I and II oropharyngeal carcinomasquamous cell carcinoma (OPSCC). (Review)
Review
OBJECTIVE
to show an overview on the treatments' options for stage I and II oropharyngeal carcinomasquamous cell carcinoma (OPSCC).
BACKGROUND
The traditional primary treatment modality of OPSCC at early stages is intensity modulated radiation therapy (IMRT). Trans-oral robotic surgery (TORS) has offered as an alternative, less invasive surgical option. Patients with human papilloma virus (HPV)-positive OPSCC have distinct staging with better overall survival in comparison with HPV-negative OPSCC patients.
METHODS
a comprehensive review of the English language literature was performed using PubMed, EMBASE, the Cochrane Library, and CENTRAL electronic databases.
CONCLUSIONS
Many trials started examining the role of TORS in de-escalating treatment to optimize functional consequences while maintaining oncologic outcome. The head-neck surgeon has to know the current role of TORS in HPV-positive and negative OPSCC and the ongoing trials that will influence its future implementation. The feasibility of this treatment, the outcomes ensured, and the side effects are key factors to consider for each patient. The variables reported in this narrative review are pieces of a bigger puzzle called tailored, evidence-based driven medicine. Future evidence will help in the construction of robust and adaptive algorithms in order to ensure the adequate treatment for the OPSCC at early stages.
Topics: Carcinoma, Squamous Cell; Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Retrospective Studies; Robotic Surgical Procedures
PubMed: 36013517
DOI: 10.3390/medicina58081050 -
JAMA Network Open Nov 2022Patients with oropharyngeal carcinoma (OPC) treated with radiotherapy often experience substantial toxic effects, even with modern techniques such as intensity-modulated...
Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Oropharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy.
IMPORTANCE
Patients with oropharyngeal carcinoma (OPC) treated with radiotherapy often experience substantial toxic effects, even with modern techniques such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) has a potential advantage over IMRT due to reduced dose to the surrounding organs at risk; however, data are scarce given the limited availability and use of IMPT.
OBJECTIVE
To compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic OPC treated with IMPT vs IMRT with or without chemotherapy.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study included patients aged 18 years or older with newly diagnosed nonmetastatic OPC who received curative-intent radiotherapy with IMPT or IMRT at a single-institution tertiary academic cancer center from January 1, 2018, to December 31, 2021, with follow-up through December 31, 2021.
EXPOSURES
IMPT or IMRT with or without chemotherapy.
MAIN OUTCOMES AND MEASURES
The main outcomes were the incidence of acute and chronic (present after ≥6 months) treatment-related adverse events (AEs) and oncologic outcomes, including locoregional recurrence (LRR), progression-free survival (PFS), and overall survival (OS). Fisher exact tests and χ2 tests were used to evaluate associations between toxic effects and treatment modality (IMPT vs IMRT), and the Kaplan-Meier method was used to compare LRR, PFS, and OS between the 2 groups.
RESULTS
The study included 292 patients with OPC (272 [93%] with human papillomavirus [HPV]-p16-positive tumors); 254 (87%) were men, 38 (13%) were women, and the median age was 64 years (IQR, 58-71 years). Fifty-eight patients (20%) were treated with IMPT, and 234 (80%) were treated with IMRT. Median follow-up was 26 months (IQR, 17-36 months). Most patients (283 [97%]) received a dose to the primary tumor of 70 Gy. Fifty-seven of the patients treated with IMPT (98%) and 215 of those treated with IMRT (92%) had HPV-p16-positive disease. There were no significant differences in 3-year OS (97% IMPT vs 91% IMRT; P = .18), PFS (82% IMPT vs 85% IMRT; P = .62), or LRR (5% IMPT vs 4% IMRT; P = .59). The incidence of acute toxic effects was significantly higher for IMRT compared with IMPT for oral pain of grade 2 or greater (42 [72%] IMPT vs 217 [93%] IMRT; P < .001), xerostomia of grade 2 or greater (12 [21%] IMPT vs 68 [29%] IMRT; P < .001), dysgeusia of grade 2 or greater (16 [28%] IMPT vs 134 [57%] IMRT; P < .001), grade 3 dysphagia (4 [7%] IMPT vs 29 [12%] IMRT; P < .001), mucositis of grade 3 or greater (10 [53%] IMPT vs 13 [70%] IMRT; P = .003), nausea of grade 2 or greater (0 [0%] IMPT vs 18 [8%] IMRT; P = .04), and weight loss of grade 2 or greater (22 [37%] IMPT vs 138 [59%] IMRT; P < .001). There were no significant differences in chronic toxic effects of grade 3 or greater, although there was a significant difference for chronic xerostomia of grade 2 or greater (6 IMPT [11%] vs 22 IMRT [10%]; P < .001). Four patients receiving IMRT (2%) vs 0 receiving IMPT had a percutaneous endoscopic gastrostomy tube for longer than 6 months.
CONCLUSIONS AND RELEVANCE
In this study, curative-intent radiotherapy with IMPT for nonmetastatic OPC was associated with a significantly reduced acute toxicity burden compared with IMRT, with few chronic toxic effects and favorable oncologic outcomes, including locoregional recurrence of only 5% at 2 years. Prospective randomized clinical trials comparing these 2 technologies and of patient-reported outcomes are warranted.
Topics: Male; Humans; Female; Middle Aged; Radiotherapy, Intensity-Modulated; Proton Therapy; Radiotherapy Dosage; Retrospective Studies; Prospective Studies; Papillomavirus Infections; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Xerostomia; Carcinoma
PubMed: 36367724
DOI: 10.1001/jamanetworkopen.2022.41538 -
Oncogene Feb 2024The incidence of oropharyngeal cancer (OPSCC) has escalated in the past few decades; this has largely been triggered by high-risk human papillomavirus (HPV). Early... (Review)
Review
The incidence of oropharyngeal cancer (OPSCC) has escalated in the past few decades; this has largely been triggered by high-risk human papillomavirus (HPV). Early cancer screening is needed for timely clinical intervention and may reduce mortality and morbidity, but the lack of knowledge about premalignant lesions for OPSCC poses a significant challenge to early detection. Biomarkers that identify individuals at high risk for OPSCC may act as surrogate markers for precancer but these are limited as only a few studies decipher the multistep progression from HPV infection to OPSCC development. Here, we summarize the current literature describing the multistep progression from oral HPV infection, persistence, and tumor development in the oropharynx. We also examine key challenges that hinder the identification of premalignant lesions in the oropharynx and discuss potential biomarkers for oropharyngeal precancer. Finally, we evaluate novel strategies to improve investigations of the biological process that drives oral HPV persistence and OPSCC, highlighting new developments in the establishment of a genetic progression model for HPV + OPSCC and in vivo models that mimic HPV + OPSCC pathogenesis.
Topics: Humans; Papillomavirus Infections; Carcinoma, Squamous Cell; Papillomaviridae; Oropharyngeal Neoplasms; Biomarkers
PubMed: 38191674
DOI: 10.1038/s41388-023-02927-9 -
Revista de Saude Publica 2023To analyze the impact of the different phases of the covid-19 pandemic on hospitalizations for oral (CaB) and oropharyngeal (CaOR) cancer in Brazil, carried out within...
OBJECTIVE
To analyze the impact of the different phases of the covid-19 pandemic on hospitalizations for oral (CaB) and oropharyngeal (CaOR) cancer in Brazil, carried out within the scope of the Brazilian Unified Health System (SUS).
METHODS
We obtained data regarding hospital admissions due to CaB and CaOR between January 2018 and August 2021 from the SUS Hospital Information System, analyzing hospital admissions as rates per 100,000 inhabitants. We divided the pandemic (January 2020 to August 2021) and pre-pandemic (January 2018 to December 2019) periods into four-month periods, comparing the pandemic period rates with analogous rates for the pre-pandemic period - for Brazil, by macro-region and by a group of procedures performed during hospitalization. We also analyzed the impact of the pandemic on the average cost of hospitalizations, expressing the results in percentage change.
RESULTS
Rates of hospitalization in the SUS due to CaB and CaOR decreased during the pandemic in Brazil. The most significant reduction occurred in the second four-month period of 2020 (18.42%), followed by decreases in the third four-month period of 2020 (17.76%) and the first and second four-month periods of 2021 (respectively, 14.64% and 17.07%), compared with 2019. The South and Southeast showed the most expressive and constant reductions between the different phases of the pandemic. Hospitalizations for clinical procedures suffered a more significant decrease than for surgical procedures. In Brazil, the average expenditure per hospitalization in the four-month pandemic periods was higher than in the reference periods.
CONCLUSION
After more than a year of the pandemic's beginning in Brazil, the SUS hospital care network for CaB and CaOR had yet to be re-established. The repressed demand for hospitalizations for these diseases, which have fast evolution, will possibly result in delays in treatment, negatively impacting the survival of these patients. Future studies are needed to monitor this situation.
Topics: Humans; Brazil; Pandemics; COVID-19; Hospitalization; Oropharyngeal Neoplasms
PubMed: 37255114
DOI: 10.11606/s1518-8787.2023057004708 -
British Journal of Cancer Apr 2021Oral and gut microbiomes have emerged as potential biomarkers in cancer. We characterised the oral and gut microbiomes in a prospective observational cohort of HPV+... (Observational Study)
Observational Study
BACKGROUND
Oral and gut microbiomes have emerged as potential biomarkers in cancer. We characterised the oral and gut microbiomes in a prospective observational cohort of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) patients and evaluated the impact of chemoradiotherapy (CRT).
METHODS
Saliva, oropharyngeal swabs over the tumour site and stool were collected at baseline and post-CRT. 16S RNA and shotgun metagenomic sequencing were used to generate taxonomic profiles, including relative abundance (RA), bacterial density, α-diversity and β-diversity.
RESULTS
A total of 132 samples from 22 patients were analysed. Baseline saliva and swabs had similar taxonomic composition (R = 0.006; p = 0.827). Oropharyngeal swabs and stool taxonomic composition varied significantly by stage, with increased oral RA of Fusobacterium nucleatum observed in stage III disease (p < 0.05). CRT significantly reduced the species richness and increased the RA of gut-associated taxa in oropharyngeal swabs (p < 0.05), while it had no effect in stool samples. These findings remained significant when adjusted by stage, smoking status and antibiotic use.
CONCLUSIONS
Baseline oral and gut microbiomes differ by stage in this HPV+ cohort. CRT caused a shift towards a gut-like microbiome composition in oropharyngeal swabs. Stage-specific features and the transitions in oral microbiome might have prognostic and therapeutic implications.
Topics: Carcinoma, Squamous Cell; Chemoradiotherapy; Female; Follow-Up Studies; Gastrointestinal Microbiome; Humans; Male; Mouth Mucosa; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Prospective Studies; Saliva
PubMed: 33750907
DOI: 10.1038/s41416-020-01253-1 -
Brazilian Journal of Otorhinolaryngology 2022To descriptively analyze the epidemiological data, clinical stage, and outcomes of oropharyngeal squamous cell carcinoma in the state of São Paulo, Brazil, and to...
OBJECTIVE
To descriptively analyze the epidemiological data, clinical stage, and outcomes of oropharyngeal squamous cell carcinoma in the state of São Paulo, Brazil, and to estimate the influence of clinical stage and treatment type on overall and disease-free survival.
METHODS
We retrospectively analyzed epidemiological data from the São Paulo Cancer Center Foundation database relative to patients with oropharyngeal squamous cell carcinoma diagnosed between 2004 and 2014 in the state of São Paulo. Univariate and multivariate Cox regression analyses were performed to assess factors associated with the outcomes. A forward stepwise selection procedure was used. Survival curves were estimated by the Kaplan-Meier method and compared by the Gehan-Breslow-Wilcoxon test.
RESULTS
A total of 8075 individuals with oropharyngeal squamous cell carcinoma were identified. Of these, 86.3% were diagnosed at an advanced stage and 13.7% at an early stage. Only 27.2% of patients were treated surgically, whereas 57.5% were treated medically. Patients undergoing surgery had longer overall survival than those receiving medical treatment in both early- and advanced-stage oropharyngeal squamous cell carcinoma. However, there was no significant difference in disease-free survival between surgical and medical treatment.
CONCLUSION
No significant difference in disease-free survival between medical and surgical treatment suggests similar complete remission rates with both approaches. Patients receiving medical treatment had shorter overall survival, which may be due to complications from chemotherapy and radiotherapy. However, we cannot confirm this relationship based on the data provided by the São Paulo Cancer Center Foundation. Prospective studies are warranted to assess whether the lower overall survival rate in patients receiving medical treatment is secondary to complications from chemotherapy and radiotherapy.
LEVEL OF EVIDENCE
2C.
Topics: Humans; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Prognosis; Carcinoma, Squamous Cell; Retrospective Studies; Brazil; Head and Neck Neoplasms; Neoplasm Staging
PubMed: 36064816
DOI: 10.1016/j.bjorl.2022.07.003 -
Journal of Otolaryngology - Head & Neck... Jun 2021Evaluate the oncologic outcomes and cost analysis of transitioning to a specimen oriented intraoperative margin assessment protocol from a tumour bed sampling protocol...
OBJECTIVE
Evaluate the oncologic outcomes and cost analysis of transitioning to a specimen oriented intraoperative margin assessment protocol from a tumour bed sampling protocol in oral cavity (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC).
STUDY DESIGN
Retrospective case series and subsequent prospective cohort study SETTING: Tertiary care academic teaching hospital SUBJECTS AND METHODS: Retrospective case series of all institutional T1-T2 OCSCC or OPSCC treated with primary surgery between January 1st 2009 - December 31st 2014. Kaplan-Meier survival estimates with log rank tests were used to compare patients based on final margin status. Cost analysis was performed for escalation of therapy due to positive final margins. Following introduction of a specimen derived margin protocol, successive prospective cohort study of T1-T4 OCSCC or OPSCC treated with primary surgery from January 1st 2017 - December 31st 2018. Analysis and comparison of both protocols included review of intraoperative margins, final pathology and treatment cost.
RESULTS
Analysis of our intra-operative tumour bed frozen section protocol revealed 15 of 116 (12.9%) patients had positive final pathology margins, resulting in post-operative escalation of therapy for 14/15 patients in the form of re-resection (7/14), radiation therapy (6/14) and chemoradiotherapy (1/14). One other patient with positive final margins received escalated therapy for additional negative prognostic factors. Recurrence free survival at 3 years was 88.4 and 50.7% for negative and positive final margins respectively (p = 0.048). Implementation of a specimen oriented frozen section protocol resulted in 1 of 111 patients (0.9%) having positive final pathology margins, a statistically significant decrease (p < 0.001). Utilizing our specimen oriented protocol, there was an absolute risk reduction for having a final positive margin of 12.0% and relative risk reduction of 93.0%. Estimated cost avoidance applying the specimen oriented protocol to our previous cohort was $412,052.812017 CAD.
CONCLUSION
Implementation of a specimen oriented intraoperative margin protocol provides a statistically significant decrease in final positive margins. This change in protocol leads to decreased patient morbidity by avoiding therapy escalation attributable only to positive margins, and avoids the economic costs of these treatments.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Humans; Male; Margins of Excision; Middle Aged; Mouth Neoplasms; Nova Scotia; Oropharyngeal Neoplasms; Otorhinolaryngologic Surgical Procedures; Prognosis; Prospective Studies; Retrospective Studies; Survival Rate
PubMed: 34154663
DOI: 10.1186/s40463-021-00501-5 -
Brazilian Journal of Otorhinolaryngology 2023According to an extensive database, the Objective is to compare surgical versus non-surgical treatment through Propensity Score (PS) for patients with Oropharyngeal...
UNLABELLED
According to an extensive database, the Objective is to compare surgical versus non-surgical treatment through Propensity Score (PS) for patients with Oropharyngeal Squamous Cell Carcinoma (OPSCC).
METHODS
We retrospectively evaluated epidemiological data from 8075 patients with OPSCC diagnosed between 2004 and 2014 and used PS matching to analyze possible prognostic factors for its outcomes with regression analyses.
RESULTS
Cox multiple regression analysis to study survival after PS matching shows that type of treatment was associated with death with a hazard ratio of 1.753 (p<0.05) of non-surgical treatment. However, it was not associated with recurrence (p>0.05). In the surgical treatment group, overall survival was 79.9% at one year, 36.4% at five years, and 20.5% at ten years. Disease-free survival was 90.1%, 64.8%, and 56.0% at 1, 5, and 10-years, respectively. In the non-surgical treatment group, overall survival was 60.6% at one year, 21.8% at five years, and 12.7% at ten years. Disease-free survival was 90.8%, 67.2%, and 57.8% at 1, 5, and 10-years, respectively.
CONCLUSION
Patients in the surgical treatment group had better outcomes related to survival. Recurrence is associated with the survival of OPSCC cancer. Recurrence-free survival is similar to both treatments.
LEVEL OF EVIDENCE
2C.
Topics: Humans; Propensity Score; Male; Retrospective Studies; Female; Oropharyngeal Neoplasms; Middle Aged; Carcinoma, Squamous Cell; Treatment Outcome; Aged; Disease-Free Survival; Neoplasm Recurrence, Local; Adult; Neoplasm Staging; Prognosis
PubMed: 37813007
DOI: 10.1016/j.bjorl.2023.101335 -
Clinical Cancer Research : An Official... Jan 2022In locally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC), (i) to investigate kinetics of human papillomavirus (HPV) circulating tumor DNA (ctDNA) and... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
In locally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC), (i) to investigate kinetics of human papillomavirus (HPV) circulating tumor DNA (ctDNA) and association with tumor progression after chemoradiation, and (ii) to compare the predictive value of ctDNA to imaging biomarkers of MRI and FDG-PET.
EXPERIMENTAL DESIGN
Serial blood samples were collected from patients with AJCC8 stage III OPSCC ( = 34) enrolled on a randomized trial: pretreatment; during chemoradiation at weeks 2, 4, and 7; and posttreatment. All patients also had dynamic-contrast-enhanced and diffusion-weighted MRI, as well as FDG-PET scans pre-chemoradiation and week 2 during chemoradiation. ctDNA values were analyzed for prediction of freedom from progression (FFP), and correlations with aggressive tumor subvolumes with low blood volume (TV) and low apparent diffusion coefficient (TV), and metabolic tumor volume (MTV) using Cox proportional hazards model and Spearman rank correlation.
RESULTS
Low pretreatment ctDNA and an early increase in ctDNA at week 2 compared with baseline were significantly associated with superior FFP ( < 0.02 and < 0.05, respectively). At week 4 or 7, neither ctDNA counts nor clearance were significantly predictive of progression ( = 0.8). Pretreatment ctDNA values were significantly correlated with nodal TV, TV, and MTV pre-chemoradiation ( < 0.03), while the ctDNA values at week 2 were correlated with these imaging metrics in primary tumor. Multivariate analysis showed that ctDNA and the imaging metrics performed comparably to predict FFP.
CONCLUSIONS
Early ctDNA kinetics during definitive chemoradiation may predict therapy response in stage III OPSCC.
Topics: Alphapapillomavirus; Biomarkers; Carcinoma, Squamous Cell; Circulating Tumor DNA; Fluorodeoxyglucose F18; Head and Neck Neoplasms; Humans; Kinetics; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck
PubMed: 34702772
DOI: 10.1158/1078-0432.CCR-21-2338