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The Cochrane Database of Systematic... Aug 2023Surgery is a common treatment option in oral cavity cancer (and less frequently in oropharyngeal cancer) to remove the primary tumour and sometimes neck lymph nodes.... (Review)
Review
BACKGROUND
Surgery is a common treatment option in oral cavity cancer (and less frequently in oropharyngeal cancer) to remove the primary tumour and sometimes neck lymph nodes. People with early-stage disease may undergo surgery alone or surgery plus radiotherapy, chemotherapy, immunotherapy/biotherapy, or a combination of these. Timing and extent of surgery varies. This is the third update of a review originally published in 2007.
OBJECTIVES
To evaluate the relative benefits and harms of different surgical treatment modalities for oral cavity and oropharyngeal cancers.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 9 February 2022.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that compared two or more surgical treatment modalities, or surgery versus other treatment modalities, for primary tumours of the oral cavity or oropharynx.
DATA COLLECTION AND ANALYSIS
Our primary outcomes were overall survival, disease-free survival, locoregional recurrence, and recurrence; and our secondary outcomes were adverse effects of treatment, quality of life, direct and indirect costs to patients and health services, and participant satisfaction. We used standard Cochrane methods. We reported survival data as hazard ratios (HRs). For overall survival, we reported the HR of mortality, and for disease-free survival, we reported the combined HR of new disease, progression, and mortality; therefore, HRs below 1 indicated improvement in these outcomes. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We identified four new trials, bringing the total number of included trials to 15 (2820 participants randomised, 2583 participants analysed). For objective outcomes, we assessed four trials at high risk of bias, three at low risk, and eight at unclear risk. The trials evaluated nine comparisons; none compared different surgical approaches for excision of the primary tumour. Five trials evaluated elective neck dissection (ND) versus therapeutic (delayed) ND in people with oral cavity cancer and clinically negative neck nodes. Elective ND compared with therapeutic ND probably improves overall survival (HR 0.64, 95% confidence interval (CI) 0.50 to 0.83; I = 0%; 4 trials, 883 participants; moderate certainty) and disease-free survival (HR 0.56, 95% CI 0.45 to 0.70; I = 12%; 5 trials, 954 participants; moderate certainty), and probably reduces locoregional recurrence (HR 0.58, 95% CI 0.43 to 0.78; I = 0%; 4 trials, 458 participants; moderate certainty) and recurrence (RR 0.58, 95% CI 0.48 to 0.70; I = 0%; 3 trials, 633 participants; moderate certainty). Elective ND is probably associated with more adverse events (risk ratio (RR) 1.31, 95% CI 1.11 to 1.54; I = 0%; 2 trials, 746 participants; moderate certainty). Two trials evaluated elective radical ND versus elective selective ND in people with oral cavity cancer, but we were unable to pool the data as the trials used different surgical procedures. Neither study found evidence of a difference in overall survival (pooled measure not estimable; very low certainty). We are unsure if there is a difference in effect on disease-free survival (HR 0.57, 95% CI 0.29 to 1.11; 1 trial, 104 participants; very low certainty) or recurrence (RR 1.21, 95% CI 0.63 to 2.33; 1 trial, 143 participants; very low certainty). There may be no difference between the interventions in terms of adverse events (1 trial, 148 participants; low certainty). Two trials evaluated superselective ND versus selective ND, but we were unable to use the data. One trial evaluated supraomohyoid ND versus modified radical ND in 332 participants. We were unable to use any of the primary outcome data. The evidence on adverse events was very uncertain, with more complications, pain, and poorer shoulder function in the modified radical ND group. One trial evaluated sentinel node biopsy versus elective ND in 279 participants. There may be little or no difference between the interventions in overall survival (HR 1.00, 95% CI 0.90 to 1.11; low certainty), disease-free survival (HR 0.98, 95% CI 0.90 to 1.07; low certainty), or locoregional recurrence (HR 1.04, 95% CI 0.91 to 1.19; low certainty). The trial provided no usable data for recurrence, and reported no adverse events (very low certainty). One trial evaluated positron emission tomography-computed tomography (PET-CT) following chemoradiotherapy (with ND only if no or incomplete response) versus planned ND (before or after chemoradiotherapy) in 564 participants. There is probably no difference between the interventions in overall survival (HR 0.92, 95% CI 0.65 to 1.31; moderate certainty) or locoregional recurrence (HR 1.00, 95% CI 0.94 to 1.06; moderate certainty). One trial evaluated surgery plus radiotherapy versus radiotherapy alone and provided very low-certainty evidence of better overall survival in the surgery plus radiotherapy group (HR 0.24, 95% CI 0.10 to 0.59; 35 participants). The data were unreliable because the trial stopped early and had multiple protocol violations. In terms of adverse events, subcutaneous fibrosis was more frequent in the surgery plus radiotherapy group, but there were no differences in other adverse events (very low certainty). One trial evaluated surgery versus radiotherapy alone for oropharyngeal cancer in 68 participants. There may be little or no difference between the interventions for overall survival (HR 0.83, 95% CI 0.09 to 7.46; low certainty) or disease-free survival (HR 1.07, 95% CI 0.27 to 4.22; low certainty). For adverse events, there were too many outcomes to draw reliable conclusions. One trial evaluated surgery plus adjuvant radiotherapy versus chemotherapy. We were unable to use the data for any of the outcomes reported (very low certainty).
AUTHORS' CONCLUSIONS
We found moderate-certainty evidence based on five trials that elective neck dissection of clinically negative neck nodes at the time of removal of the primary oral cavity tumour is superior to therapeutic neck dissection, with increased survival and disease-free survival, and reduced locoregional recurrence. There was moderate-certainty evidence from one trial of no difference between positron emission tomography (PET-CT) following chemoradiotherapy versus planned neck dissection in terms of overall survival or locoregional recurrence. The evidence for each of the other seven comparisons came from only one or two studies and was assessed as low or very low-certainty.
Topics: Humans; Immunotherapy; Mouth; Neck; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Randomized Controlled Trials as Topic
PubMed: 37650478
DOI: 10.1002/14651858.CD006205.pub5 -
Anticancer Research Sep 2023Otorhinolaryngology tradition is that tonsillectomy (TE) is conducted among children and adolescents for obstructive sleep apnea secondary to adenotonsillar hypertrophy... (Meta-Analysis)
Meta-Analysis Review
Tonsillectomy as Prevention of Tonsil and Base of Tongue Cancer: Systematic Review and Meta-analysis on the Immuno-Oncological Effect of One Among the Most Common Surgeries in the World.
Otorhinolaryngology tradition is that tonsillectomy (TE) is conducted among children and adolescents for obstructive sleep apnea secondary to adenotonsillar hypertrophy and in adults for chronic disease of the tonsils and adenoids (recurrent tonsillitis). Nevertheless, over the last 50 years, we have observed a decline in TE worldwide. As a result, there is an emerging concern of a correlated possible increased risk of tonsil cancer (TC) and other subtypes of oropharyngeal squamous cell carcinoma. Since the available data on such topics are limited and controversial, our aim was to elucidate the impact of TE on the incidence mainly of TC through a systematic review of the literature and a meta-analysis of the studies. After a thorough search, 7 retrospective studies were considered eligible for review and meta-analysis (MA). At MA, patients with a history of TE seem to show a reduced risk of TC but a higher predisposition for base of tongue (BOT) cancer (p<0.001): however, the elevated heterogeneity of the studies hampers drawing firm and convincing conclusions (statistical inconsistency >95%). In future, randomized control trials will be welcome to elucidate the prophylactic role of TE against TC and its real impact on BOT cancer.
Topics: Adolescent; Adult; Child; Humans; Palatine Tonsil; Tonsillectomy; Tongue Neoplasms; Retrospective Studies; Oropharyngeal Neoplasms; Tonsillar Neoplasms; Laryngeal Neoplasms; Head and Neck Neoplasms
PubMed: 37648322
DOI: 10.21873/anticanres.16575 -
The Laryngoscope Apr 2024The immune microenvironment of HPV-associated (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) (HPV+OPSCCs) differs from that of HPV-independent oropharyngeal... (Review)
Review
OBJECTIVE
The immune microenvironment of HPV-associated (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) (HPV+OPSCCs) differs from that of HPV-independent oropharyngeal cancers (HPV-independent OPSCCs). The literature on the subject is very abundant, demanding an organized synthesis of this wealth of information to evaluate the hypothesis associating the favorable prognosis of HPV+OPSCC patients with a different immune microenvironment. A systematic review of the literature was conducted regarding the microenvironment of HPV+OPSCCs.
DATA SOURCE
MEDLINE/PubMed, Embase, and Cochrane Library databases.
REVIEW METHODS
A literature search was performed following PRISMA guidelines (Moher D. PLoS Med. 2009). The PEO (Population, Exposure, and Outcome) framework is detailed as follows: P: patients with oropharyngeal squamous cell carcinomas, E: human papillomavirus (HPV), and O: histological and immunological composition of the tumoral microenvironment (TME). No meta-analysis was performed.
RESULTS
From 1,202 studies that were screened, 58 studies were included (n = 6,474 patients; n = 3,581 (55%) HPV+OPSCCs and n = 2,861(45%) HPV-independent OPSCCs). The presence of tumor-infiltrating lymphocytes (TIL), CD3+ in 1,733 patients, CD4+ in 520 patients, and CD8+ (cytotoxic T lymphocytes (CTL)) in 3,104 patients, and high levels of PD-L1 expression in 1,222 patients is strongly correlated with an improved clinical outcome in HPV+OPSCCs.
CONCLUSION
This systematic review provides the most comprehensive information on the immune microenvironment of HPV+OPSCCs to date. Tumor-infiltrating lymphocytes and PD-L1 expression are associated with a favorable prognosis. B, CD8+ and resident memory cells densities are higher in HPV+OPSCCs. The importance of myeloid lineages is still a matter of debate and research.
LEVEL OF EVIDENCE
NA Laryngoscope, 134:1507-1516, 2024.
Topics: Humans; Prognosis; B7-H1 Antigen; Human Papillomavirus Viruses; Papillomavirus Infections; Papillomaviridae; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Tumor Microenvironment
PubMed: 37642393
DOI: 10.1002/lary.31010 -
Journal of Robotic Surgery Oct 2023To compare the effectiveness of transoral robotic surgery (TORS) and non-robotic surgeries (NRES) in patients with oropharyngeal squamous cell carcinoma (OPSCC), medical... (Meta-Analysis)
Meta-Analysis
To compare the effectiveness of transoral robotic surgery (TORS) and non-robotic surgeries (NRES) in patients with oropharyngeal squamous cell carcinoma (OPSCC), medical databases were searched including PubMed, Web of Science, Medline, Embase, and Cochrane Library up to January 2023. The methodology follows PRISMA guidelines, including the PRISMA flow diagram. Data from the included studies were extracted independently by two researchers. Seven studies involving five hundred seventy-seven patients were included. Of these, 275 underwent TORS and 302 underwent NRES. The disease-free survival rate was significantly higher in the TORS group than in the NRES group (OR = 3.43, 95% CI 1.92-6.15, P < 0.0001). However, there were no significant differences in positive surgical margins, hospital stays, operation time, blood loss, postoperative bleeding rate, perioperative tracheostomy, perioperative feeding tube, and overall survival rate. These findings can initially guide the preoperative counseling of TORS in patients with OPSCC, and preliminarily confirm that the adoption of TORS deserves careful consideration.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Robotic Surgical Procedures; Carcinoma, Squamous Cell; Oropharyngeal Neoplasms; Head and Neck Neoplasms; Retrospective Studies
PubMed: 37542007
DOI: 10.1007/s11701-023-01689-6 -
Cancer Medicine Sep 2023HPV infection can cause cancer, and standard treatments often result in recurrence. The extent to which liquid biopsy using HPV circulating tumor DNA (HPV ctDNA) can be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
HPV infection can cause cancer, and standard treatments often result in recurrence. The extent to which liquid biopsy using HPV circulating tumor DNA (HPV ctDNA) can be used as a promising marker for predicting recurrence in HPV-related cancers remains to be validated. Here we conducted a systematic review and meta-analysis to assess its effectiveness in predicting treatment response.
METHODS
We conducted a systematic literature search of online databases, including PubMed, Embase, Scopus, and the Cochrane Library, up to December 2022. The goal was to identify survival studies that evaluated the potential of plasma HPV ctDNA at baseline and end-of-treatment (EoT) in predicting recurrence of related cancers. Hazard ratios were estimated directly from models or extracted from Kaplan-Meier plots.
RESULTS
The pooled effect of HPV ctDNA presence on disease recurrence was estimated to be HR = 7.97 (95% CI: [3.74, 17.01]). Subgroup analysis showed that the risk of recurrence was HR = 2.17 (95% CI: [1.07, 4.41]) for baseline-positive cases and HR = 13.21 (95% CI: [6.62, 26.36]) for EoT-positive cases. Significant associations were also observed between recurrence of oropharyngeal squamous cell carcinoma (HR = 12.25 (95% CI: [2.62, 57.36])) and cervical cancer (HR = 4.60 (95% CI: [2.08, 10.17])) in plasma HPV ctDNA-positive patients.
CONCLUSIONS
The study found that HPV ctDNA detection can predict the rate of relapse or recurrence after treatment, with post-treatment measurement being more effective than baseline assessment. HPV ctDNA could be used as a surrogate or incorporated with other methods for detecting residual disease.
Topics: Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Circulating Tumor DNA; Neoplasm Recurrence, Local; Head and Neck Neoplasms
PubMed: 37492996
DOI: 10.1002/cam4.6377 -
Oral Oncology Oct 2023Transoral robotic surgery (TORS) has been used in the salvage setting for head and neck cancers both with and without reconstruction. The complications of salvage TORS...
BACKGROUND
Transoral robotic surgery (TORS) has been used in the salvage setting for head and neck cancers both with and without reconstruction. The complications of salvage TORS and the effect of reconstruction on complications has not been studied.
OBJECTIVE
To study the complications of salvage TORS and examine the effect of reconstruction on complication rates.
METHOD
An electronic search of the English- language literature using PubMed, Medline, and the Cochrane database was conducted and a systematic review performed in accordance with PRISMA guidelines (CRD42020181057).
RESULTS
A total of 23 studies including 533 patients have been published on salvage TORS.The average patient age was 61.2 years.Prior treatment was described for 420 patients.205 (48.8%) underwent prior definitive radiotherapy (RT).160 (38.1%) underwent definitive chemoradiotherapy (CRT).Only 55 (13.1%) had prior surgery.Overall, there were 158 complications with a pooled rate of 33.6% (95%CI: 25.4-42.3%).77 were major complications requiring surgical intervention with a pooled rate of 18.9% (95% CI: 14.8-23.3%).The number of patients undergoing reconstruction among salvage cases in the literature is 59 (9.19%), with 24 local flaps and 25 microvascular free flaps.Reconstruction was associated with lower overall hemorrhage rates but had no impact on major hemorrhage rates.
CONCLUSIONS
The pooled incidence rates of major complications, major POH and emergency tracheostomy following salvage TORS are 18.9%, 10.5%, and 4.4%.The rate of death following salvage TORS is 3.6%. Reconstruction was associated with lower overall hemorrhage rate after salvage TORS but had no impact on major postoperative hemorrhage rates.
Topics: Humans; Middle Aged; Oropharyngeal Neoplasms; Robotic Surgical Procedures; Head and Neck Neoplasms; Chemoradiotherapy
PubMed: 37454544
DOI: 10.1016/j.oraloncology.2023.106467 -
Asia-Pacific Journal of Clinical... Apr 2024Return to work (RTW) is a marker of functional recovery for working-age cancer survivors. Identifying factors that impact on RTW in cancer survivors is an essential step... (Review)
Review
Return to work (RTW) is a marker of functional recovery for working-age cancer survivors. Identifying factors that impact on RTW in cancer survivors is an essential step to guide further research and interventions to support RTW. This systematic review aimed to identify nontreatment, non-cancer-related variables impacting RTW in Australian cancer survivors. A systematic search was conducted in EMBASE, PsycINFO, CINAHL, PubMed, and Google Scholar. Studies were eligible if they included: (1) adults living post diagnosis of malignancy; (2) quantitative data for nontreatment, non-cancer-related variables impacting RTW; (3) only Australian participants. Included studies were critically appraised, and relevant data extracted and synthesized narratively. Six studies were included in the review, published between 2008 and 2020. Studies were of variable quality and mixed methodologies. One study included malignancies of any type with the remainder focusing on survivors of colorectal cancer (n = 3), oropharyngeal cancer (n = 1), and glioblastoma multiforme (n = 1). Multiple factors were related to RTW in individual studies, including older age, presence of three or more comorbidities, fewer work hours pre-morbidly, lower body mass index, longer than recommended sleep duration, and not having private health insurance; however, there was limited consistency in findings between studies. Other variables examined included: occupation type, household income, healthy lifestyle behaviors, flexibility, and duration of employment with workplace; however, no significant associations with RTW were reported. Further research is required to gather compelling evidence on factors that influence RTW in Australian cancer survivors.
Topics: Adult; Humans; Cancer Survivors; Return to Work; Australia; Survivors; Neoplasms
PubMed: 37357383
DOI: 10.1111/ajco.13973 -
European Archives of... Oct 2023Recurrent head and neck squamous cell carcinomas (HNSCC) are frequently managed with salvage surgery, but the impact these operations have on function and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recurrent head and neck squamous cell carcinomas (HNSCC) are frequently managed with salvage surgery, but the impact these operations have on function and quality-of-life (QoL) is understudied. This review aimed to provide a quantitative and qualitative assessment of the functional and QoL effects of salvage surgical procedures.
METHODS
Systematic review and meta-analysis were conducted of studies reporting QoL and function following salvage HNSCC resections.
RESULTS
The search identified 415 articles and 34 were selected for inclusion. Pooled random effects analysis revealed long-term feeding and tracheostomy tube rates of 18% and 7%. Pooled long-term feeding tube rates in open oral and oropharyngeal, transoral robotic, total and partial laryngectomy surgeries were 41%, 25%, 11% and 4%. Eight studies used validated QoL questionnaires.
CONCLUSIONS
Functional and QoL outcomes from salvage surgery are acceptable, but appear to be worse following open procedures. Prospective studies measuring changes over time are needed to assess these procedures impact on patient well-being.
Topics: Humans; Head and Neck Neoplasms; Salvage Therapy; Quality of Life; Squamous Cell Carcinoma of Head and Neck; Neoplasm Recurrence, Local
PubMed: 37329358
DOI: 10.1007/s00405-023-08056-z -
Molecular Oral Microbiology Aug 2023Squamous cell carcinoma of the oral cavity (OSCC) is the most common head-and-neck malignancy. Importantly, we are experiencing an alarming rise in the incidence of... (Meta-Analysis)
Meta-Analysis Review
Squamous cell carcinoma of the oral cavity (OSCC) is the most common head-and-neck malignancy. Importantly, we are experiencing an alarming rise in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) globally. Oncogenic viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV), are known to be co-associated with OSCC and OPSCC cases. However, the reported incidence of HPV and EBV co-infection in OSCCs and OPSCCs globally is unknown. To address this, we performed a formal meta-analysis and systematic review on published studies that report the detection of both EBV and HPV in OSCCs and OPSCCs. Our analysis revealed 18 relevant studies out of a total of 1820 cases (1181 from the oral cavity and 639 from the oropharynx). Overall, HPV and EBV co-infection was found in 11.9% of OSCC and OPSCC cases combined (95% CI: 8%-14.1%). Based on anatomical subsite, dual positivity estimates were 10.5% (95% CI: 6.7%-15.1%) for OSCC and 14.2% (95% CI: 9.1%-21.3%) for OPSCC. The highest dual positivity rates described were in European countries: for OSCC 34.7% (95% CI: 25.9%-44.6%) in Sweden and for OPSCC, 23.4% (95% CI: 16.9%-31.5%) in Poland. Given these substantive prevalence rates, the value of detecting dual infection in the diagnosis and prognosis of these cancers deserves careful longitudinal studies, as do implications for cancer prevention and therapy. We further proposed molecular mechanisms that could explain how HPV and EBV could co-contribute to the aetiology of OSCCs and OPSCCs.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Human Papillomavirus Viruses; Papillomavirus Infections; Coinfection; Head and Neck Neoplasms
PubMed: 37014754
DOI: 10.1111/omi.12412 -
Journal of Robotic Surgery Aug 2023Transoral robotic surgery (TORS) approach for the treatment of oropharyngeal cancer allows for reduced patient morbidity, amongst other advantages over the traditional... (Review)
Review
Transoral robotic surgery (TORS) approach for the treatment of oropharyngeal cancer allows for reduced patient morbidity, amongst other advantages over the traditional lip-splitting mandibulotomy method. Free-flap reconstruction is commonly utilized in head and neck cancer surgeries; however, safety and outcomes of this technique in TORS procedures have not been well studied. The objective of this study was to perform a systematic review to evaluate the efficacy and safety of TORS with free-flap reconstruction (TORS-FFR) for oropharyngeal cancer. A systematic search of Scopus, EMBASE, CINAHL and PubMed databases was completed. Following PRISMA guidelines, case series/reports, retrospective and prospective cohort studies were included. Primary outcomes measured were deaths and complication rates associated with TORS-FFR for oropharyngeal cancers. Secondary outcomes included functional swallowing and airway outcomes, operative time and length of hospital stay. Twenty-one studies met the inclusion criteria comprising a total of 132 patients. The mean patient age was 58.4 years. The most frequent complication was infection (8.9%) followed by flap wound dehiscence (4.2%). The average total operative time was 710 min (n = 48), while average length of hospital stay was 13.5 days (n = 48). Reconstructions were most commonly fashioned from radial forearm free flaps (RFFF), with anterolateral thigh flaps (ALT) representing the second most common free-flap subtype. TORS-FFR procedures for oropharyngeal cancer are safe, with low serious complication rates. This surgical approach may be associated with decreased length of hospital stay; however, further studies are required to better characterize post-operative outcomes.Level of evidence 1a.
Topics: Humans; Middle Aged; Retrospective Studies; Robotic Surgical Procedures; Prospective Studies; Oropharyngeal Neoplasms; Free Tissue Flaps
PubMed: 36964850
DOI: 10.1007/s11701-023-01572-4