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Clinical & Experimental Metastasis Jun 2022Infection with HPV virus and exposure to extrinsic carcinogens are the main causative factors for oropharyngeal squamous cell carcinoma (OPSCC). While HPV-related OPSCC... (Review)
Review
Infection with HPV virus and exposure to extrinsic carcinogens are the main causative factors for oropharyngeal squamous cell carcinoma (OPSCC). While HPV-related OPSCC typically shows a better prognosis and may be a candidate for de-intensification therapy, there is a subset of HPV-related cancers that show aggressive phenotype with frequent metastatic spread. The identification and refinement of molecular markers can better serve for prediction of prognosis and thus improve treatment decisions and outcome. We conducted a systematic review according to the PRISMA guidelines of all relevant studies addressing novel biomarkers in publications prior to July 2021. We identified studies that evaluated the association between molecular markers and prognosis in HPV-positive OPSCC. Full-text publications were entirely reviewed, classified, and selected if a clear predictive/prognostic value was seen in patients with HPV-positive OPSCC. Furthermore, a functional analysis of the target genes was conducted to understand biological processes and molecular pathways impacting on HPV-positive OPSCC outcomes. The systematic review yielded a total of 14 studies that matched the inclusion and exclusion criteria. Differential expression was identified for 31 different biomarkers. The first common pattern identified was the association of HPV-related circulating antibodies to activated immune function. Second, gene-gene interaction analysis further identified interacting gene networks tightly implicated in hypoxia tumor metabolism including the Warburg effect. Survival in HPV-positive OPSCC can be predicted by distinct selective biomarkers mainly indicative of immune host response and oxidative metabolism. Among these markers, some were identified to be unsuitable for HPV-positive de-escalation trials aimed at improving patients' quality of life.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Quality of Life; Squamous Cell Carcinoma of Head and Neck
PubMed: 35084607
DOI: 10.1007/s10585-022-10148-9 -
Seminars in Radiation Oncology Jul 2023Head and neck cancer is notoriously challenging to treat in part because it constitutes an anatomically and biologically diverse group of cancers with heterogeneous... (Review)
Review
Head and neck cancer is notoriously challenging to treat in part because it constitutes an anatomically and biologically diverse group of cancers with heterogeneous prognoses. While treatment can be associated with significant late toxicities, recurrence is often difficult to salvage with poor survival rates and functional morbidity. Thus, achieving tumor control and cure at the initial diagnosis is the highest priority. Given the differing outcome expectations (even within a specific sub-site like oropharyngeal carcinoma), there has been growing interest in personalizing treatment: de-escalation in selected cancers to decrease the risk of late toxicity without compromising oncologic outcomes, and intensification for more aggressive cancers to improve oncologic outcomes without causing undue toxicity. This risk stratification is increasingly accomplished using biomarkers, which can represent molecular, clinicopathologic, and/or radiologic data. In this review, we will focus on biomarker-driven radiotherapy dose personalization with emphasis on oropharyngeal and nasopharyngeal carcinoma. This radiation personalization is largely performed on the population level by identifying patients with good prognosis via traditional clinicopathologic factors, although there are emerging studies supporting inter-tumor and intra-tumor level personalization via imaging and molecular biomarkers.
Topics: Humans; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Oropharyngeal Neoplasms; Prognosis; Biomarkers
PubMed: 37331788
DOI: 10.1016/j.semradonc.2023.03.013 -
Head & Neck May 2022Human Papillomavirus (HPV) related oropharyngeal carcinoma (OPC) carries a better prognosis compared with HPV-counterparts, thereby pushing the adoption of... (Meta-Analysis)
Meta-Analysis Review
Human Papillomavirus (HPV) related oropharyngeal carcinoma (OPC) carries a better prognosis compared with HPV-counterparts, thereby pushing the adoption of de-intensification treatment approaches as new strategies to preserve superior oncologic outcomes while minimizing toxicity. We evaluated the effect of treatment de-intensification in terms of overall survival (OS), progression-free survival (PFS), locoregional and distant control (LRC and DM) by selecting prospective or retrospective studies, providing outcome data with reduced intensification versus standard curative treatment in HPV+ OPC patients, with a systematic analysis till September 2020. The primary outcome of interest was OS. Secondary endpoints were PFS, LRC, and DM expressed as HR. A total of 55 studies (from 1393 screened references) were employed for quantitative synthesis for 38 929 patients. Among n = 48 studies with data available, de-intensified treatments reduced OS in HPV+ OPCs (HR = 1.33, 95% CI 1.17-1.52; p < 0.01). In de-escalated treatments, PFS was also decreased (HR = 2.11, 95% CI 1.65-2.69; p < 0.01). Compared with standard treatments, reduced intensity approaches were associated with reduced locoregional and distant disease control (HR = 2.51, 95% CI 1.75-3.59; p < 0.01; and HR = 1.9, 95% CI 1.25-2.9; p < 0.01). Chemoradiation improved survival in a definitive curative setting compared with radiotherapy alone (HR = 1.42, 95% CI 1.16-1.75; p < 0.01). When adjuvant treatments were compared, standard and de-escalation strategies provided similar OS. In conclusion, in patients with HPV+ OPC, de-escalation treatments should not be widely and agnostically adopted in clinical practice, as therein lies a concrete risk of offering a sub-optimal treatment to patients.
Topics: Alphapapillomavirus; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prospective Studies; Retrospective Studies
PubMed: 35238114
DOI: 10.1002/hed.27019 -
Radiographics : a Review Publication of... 2019During the past decade and a half, the most common cause of oropharyngeal squamous cell carcinoma (OPSCC) has shifted from tobacco and alcohol to the human... (Review)
Review
During the past decade and a half, the most common cause of oropharyngeal squamous cell carcinoma (OPSCC) has shifted from tobacco and alcohol to the human papillomavirus (HPV). HPV-driven p16-positive OPSCC and tobacco-related OPSCC differ in their underlying molecular and genetic profiles, socioeconomic demographics, and response to treatment. HPV-related OPSCC tends to occur in younger patients and has a significantly better response to treatment and excellent prognosis. The stark contrast in prognosis-with around 90% overall 5-year survival for HPV-related p16-positive OPSCC and 40% for non-HPV-related p16-negative OPSCC-has prompted major changes in the eighth edition of the staging manual of the AJCC (American Joint Committee on Cancer). The past 10-15 years have also witnessed major advances in surgery, radiation therapy (RT), and systemic therapy. Minimally invasive surgery has come of age, with transoral robotic procedures and laser microsurgery. Intensity-modulated RT (IMRT) and more recently proton-beam RT have markedly improved the conformity of RT, with an ability to precisely target the cancer and cancer-bearing regions while sparing normal structures and significantly reducing long-term treatment-related morbidity. Progress in systemic therapy has come in the form of immunotherapy and targeted agents such as cetuximab. Owing to the better prognosis of HPV-driven OPSCC as well as the morbidity associated with treatment, de-escalation of therapy via multiple strategies is being explored. The article reviews the advances in diagnosis and multidisciplinary management of OPSCC in the HPV era.RSNA, 2019.
Topics: Age Distribution; Alcohol Drinking; Carcinoma, Squamous Cell; Cell Cycle; Chemotherapy, Adjuvant; Clinical Trials as Topic; Combined Modality Therapy; Diagnostic Imaging; Disease Management; Human papillomavirus 16; Humans; Immunotherapy; Lymphatic Metastasis; Neoplasm Staging; Oncogene Proteins, Viral; Oral Surgical Procedures; Oropharyngeal Neoplasms; Papillomavirus E7 Proteins; Papillomavirus Infections; Prognosis; Radiotherapy, Adjuvant; Repressor Proteins; Risk Factors; Salvage Therapy; Smoking
PubMed: 31603733
DOI: 10.1148/rg.2019190007 -
The British Journal of Oral &... Jan 2023Social habits such as smoking and drinking alcohol are well-known causative agents for oral and oropharyngeal squamous cell carcinoma (OSCC/OPSCC). Human papillomavirus... (Review)
Review
Social habits such as smoking and drinking alcohol are well-known causative agents for oral and oropharyngeal squamous cell carcinoma (OSCC/OPSCC). Human papillomavirus (HPV) is a known causative agent for OPSCC. However, we often encounter patients with no identifiable risk factors. There is growing evidence of the role of occupational carcinogens in the pathogenesis of oral cancer. The aim of this study therefore was to identify any occupational carcinogens linked to oral cancer. We carried out a systematic review of the literature using PubMed, EMBASE, and Medline, along with a retrospective review of patients treated in a regional unit over 25 years. Occupations were classified based on the UK Standard of Classification 2020. Data analysis was completed using the chi-squared test. A total of 17 papers met the inclusion criteria for review. In our retrospective study a total of 874 patients were identified of whom 31% were blue-collar workers, 32.8% were white-collar workers, 20.2% were unemployed/housewives, and 16% workers in other occupations. The majority of blue-collar workers were in the construction industry and had maximum exposure to hydrocarbons and exhaust fumes. The aetiology of oral and oropharyngeal SCC is multifactorial and there is no consensus on the role of occupational carcinogens. We showcase our patient cohort and discuss the occupational exposures that appear to make them susceptible to OSCC and OPSCC. Further multicentre studies are required to enable us to understand fully the pathogenesis of oral cancer and help us to inform relevant organisations, the aim being to reduce the incidence of occupation-related cancer.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Retrospective Studies; Oropharyngeal Neoplasms; Mouth Neoplasms; Carcinoma, Squamous Cell; Papillomavirus Infections; Occupational Exposure; Head and Neck Neoplasms; Carcinogens
PubMed: 36443129
DOI: 10.1016/j.bjoms.2022.11.001 -
Auris, Nasus, Larynx Aug 2022Over time, the primary treatment modality of oropharyngeal squamous cell cancers (OPSCC) is intensity-modulated radiation therapy (IMRT), eventually associated with... (Review)
Review
Over time, the primary treatment modality of oropharyngeal squamous cell cancers (OPSCC) is intensity-modulated radiation therapy (IMRT), eventually associated with chemotherapy (CHT). This treatment modality is preferred for reduced impact on the quality of life rather than aggressive open surgical approaches. The advent of TransOral Robotic Surgery (TORS) has rediscovered the role of surgery in the treatment of OPSCC. Although the primary chemoradiation therapy (CRT) and transoral robotic surgery (TORS) are competing for similar oncologic results, CRT may result in significant functional complaints such as severe dysphagia and feeding tube dependence and, on the other hand, TORS might result in surgical defects depending on the size of the resection and anatomic location. Nevertheless, TORS may intercept the locoregionally advanced population through pathologic downstaging as well as the potential for improvement in oncologic outcomes. The available reconstructive options allow an expanding role of this minimally invasive surgery, even in locally advanced tumours. Finally, the surgical management of OPSCC with TORS identifies areas of opportunity in shortening the overall treatment package time compared to traditional surgery.
Topics: Chemoradiotherapy; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Quality of Life; Robotic Surgical Procedures; Squamous Cell Carcinoma of Head and Neck
PubMed: 35101284
DOI: 10.1016/j.anl.2022.01.011 -
The Laryngoscope Jul 2019Based on current guidelines, surgical and nonsurgical therapies are viable frontline treatment for patients with locoregional oropharyngeal carcinoma (OPC). We sought to... (Comparative Study)
Comparative Study
OBJECTIVES/HYPOTHESIS
Based on current guidelines, surgical and nonsurgical therapies are viable frontline treatment for patients with locoregional oropharyngeal carcinoma (OPC). We sought to compare financial parameters between chemoradiation and transoral robotic surgery (TORS) in this patient population.
STUDY DESIGN
Case-control study.
METHODS
In this study we identified patients with selected American Joint Committee on Cancer 7th Edition stage II to IVa OPC treated with TORS between January 2013 and December 2014. Fifteen patients who underwent TORS were stage matched with 15 patients treated with chemoradiation. Total charges and cost data for each patient were analyzed at 4-month and 1-year time points; functional and oncologic outcomes were assessed.
RESULTS
There were no significant differences in functional and oncologic outcomes. Patients undergoing TORS had a longer inpatient hospital stay, and most required a nasogastric tube for an average of 3.5 days. There were no local or regional recurrences. Across all time points, the TORS group had lower charges and costs compared to the chemoradiation group, with 14% lower costs at 1 year. In the chemoradiation group, nearly two-thirds of costs came from radiation therapy and pharmacy expenses. Chemotherapy accounted for most pharmacy costs. The costs of operating the surgical robot accounted for a about half of surgical costs.
CONCLUSIONS
Selected patients with stage II to IVa oropharyngeal carcinoma treated with TORS may incur lower costs than those treated nonsurgically. With rising healthcare spending, the financial impact of treatment might be considered for those patients eligible for treatment regimens with comparable functional and oncologic outcomes.
LEVEL OF EVIDENCE
3b Laryngoscope, 129:1604-1609, 2019.
Topics: Case-Control Studies; Chemoradiotherapy; Costs and Cost Analysis; Female; Humans; Intubation, Gastrointestinal; Length of Stay; Male; Middle Aged; Neoplasm Staging; Oropharyngeal Neoplasms; Robotic Surgical Procedures
PubMed: 30485445
DOI: 10.1002/lary.27544 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Sep 2023To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. A retrospective analysis was performed on 468 pathologically...
To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. A retrospective analysis was performed on 468 pathologically confirmed oropharyngeal cancer as the primary tumor patients with p16 status, excluded distant metastasis, and admitted to the Chinese Academy of Medical Sciences from January 2010 to December 2020. The clinical features and prognosis of the secondary primary tumor were analyzed. Among 468 patients with oropharyngeal cancer treated at initial diagnosed, 222 cases were P16-negative. With a median follow-up time of 64.3 months, 66 cases developed second primary cancer, with an incidence of 29.3%, among which 63.6%(42/66) were synchronous and 36.4%(24/66) were heterochronous, esophagus was the most commonly involved site. The 5-year OS of p16-negative oropharyngeal carcinoma with synchronous second primary cancer, without second primary cancer and with heterogeneous second primary cancer were 26.3% and 57.3% and 73.2%(=0.001); The second primary cancer accounted for 11.2%(12/107) of the deaths in the whole group, among them, the heterochronous second primary accounted for 75.0%(9/12). There were 246 patients with p16 positive, with a median follow-up time of 52.4 months, 20 patients developed second primary cancer(8.1%). Among them, 65.0%(13/20) were synchronous and 35.0%(7/20) were heterochronous. Esophagus was the most commonly involved site. The 4-year OS of p16-positive with synchronous, heterochronous and non-second primary cancer group were 51.9%, 80.7% and 83.3%. Secondary primary cancer accounted for 3.8%(2/52) of all deaths in p16 positvie group. The incidence of second primary cancer of p16 positive and negative oropharyngeal carcinoma were different. The esophagus was the most commonly involved site regardless of p16 status. Regardless of p16 status, the survival of patients with synchronous second primary cancer was worse than those without second primary cancer. For p16-negative oropharyngeal carcinoma, the prognosis was better in patients with heterogeneous second primary cancer, the second primary cancer is one of the main causes of death.
Topics: Humans; Carcinoma; Oropharyngeal Neoplasms; Retrospective Studies; Neoplasms, Second Primary
PubMed: 37640995
DOI: 10.13201/j.issn.2096-7993.2023.09.007 -
Oncology (Williston Park, N.Y.) Jul 2023Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC), which accounts for an increasing proportion of all head and neck cancers, represents a... (Review)
Review
Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC), which accounts for an increasing proportion of all head and neck cancers, represents a specific entity with distinct clinical and molecular characteristics. It is now firmly established that patients with HPV-positive oropharyngeal SCC have a significantly improved prognosis because this variant has exquisite radiosensitivity compared with HPV-negative oropharyngeal SCC; thus, it can be targeted with de-escalated approaches using reduced doses of radiation and/or chemotherapy. The overriding goal of de-escalation is to maintain the high cure and survival rates associated with traditional approaches while reducing the incidence of both short- and long-term toxicity. Although the exact reason for the improved radiosensitivity of HPV-positive oropharyngeal carcinoma is unclear, prospective studies have now been published demonstrating that de-escalated radiation can successfully maintain high rates of cure and preserve the quality of life for appropriately selected patients with this disease. However, these studies have been complicated by such factors as the relatively limited sample sizes, as well as the variability in treatment, inclusion criteria, and follow-up. How treatment paradigms will evolve, particularly in the era of precision medicine, is a provocative question and is the subject of this review.
Topics: Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Prospective Studies; Quality of Life; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Papillomaviridae
PubMed: 37499250
DOI: 10.46883/2023.25921000 -
The Laryngoscope Jun 2021The role of locoregional radiotherapy for metastatic oropharyngeal squamous cell cancer (OPSCC) is unclear. We investigated the impact of head and neck radiotherapy on...
OBJECTIVES
The role of locoregional radiotherapy for metastatic oropharyngeal squamous cell cancer (OPSCC) is unclear. We investigated the impact of head and neck radiotherapy on survival in de novo metastatic OPSCC patients who received systemic therapy.
METHODS
We queried the NCDB from 2004-2015 for metastatic OPSCC patients at diagnosis with known HPV-status who received systemic therapy. The association of head and neck radiotherapy with overall survival was analyzed using the Kaplan-Meier method, Cox proportional hazards model, and propensity score-matched analysis adjusting for demographic and disease-specific prognostic factors.
RESULTS
Of the 2,139 patients with metastatic OPSCC who presented with metastases and received systemic treatment, we identified 556 patients with known HPV-status. Among these 556 patients, 49% were HPV-positive and 56% received head and neck radiotherapy. With a median follow-up of 17.5 months (IQR 6.0-163.4 months), radiotherapy was associated with significantly improved 1-year OS (67% vs 58%, log-rank P < .001) which remained significant on MVA (HR 0.78 95% CI 0.62-0.97 P = .029). In HPV-status subgroup analysis, a survival benefit was identified in HPV-positive patients (1-year OS 77% vs 67%, log-rank P < .001) but not in HPV-negative patients. Results were consistent on a propensity score-matched analysis of 212 HPV-positive matched patients (HR 0.66, 95% CI 0.49-0.83, P < .001).
CONCLUSION
The survival of metastatic OPSCC remains limited. In this large series of patients with known HPV-status, head and neck radiotherapy was associated with longer survival in those with HPV-associated disease. These data could guide management of this challenging group of patients for head and neck cancer practitioners.
LEVEL OF EVIDENCE
3 Laryngoscope, 131:E1847-E1853, 2021.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis; Propensity Score; Survival Rate
PubMed: 33141455
DOI: 10.1002/lary.29245