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Journal of Clinical Medicine Aug 2022Adenoid cystic carcinoma (AdCC) is a rare tumor whose clinical course is burdened by local recurrence and distant dissemination. Lymph node metastasis is not believed... (Review)
Review
Adenoid cystic carcinoma (AdCC) is a rare tumor whose clinical course is burdened by local recurrence and distant dissemination. Lymph node metastasis is not believed to be common and its clinical impact is controversial. The aim of this study was to determine: (1) the prevalence of occult metastasis at diagnosis in cN0 head and neck AdCC, (2) its prognostic role, and (3) the consequent need to perform elective neck dissection (END). A systematic review and meta-analyses following PRISMA guidelines was performed. PubMed, Embase, and Central databases were questioned up to July 2021 to identify studies reporting on the prevalence of occult neck metastases in head and neck AdCC. A single-arm meta-analysis was then performed to determine the pooled prevalence of occult lymph node metastases among the retained studies. Of the initial 6317 studies identified, 16 fulfilled the inclusion criteria, and they were included in the meta-analysis. Of a population of 7534 patients, 2530 cN0 patients were treated with END, which revealed 290/2530 cases of occult metastases (pN+/cN0). Meta-analysis of the results of END in the 16 studies estimated an overall prevalence of occult metastases at diagnosis of 17%. No further subgroup analysis was possible to identify factors influencing lymph node involvement and the prognostic role of END. Taking 20% as an historically proposed cut off, a 17% prevalence of occult metastases represents a borderline percentage to get a definitive conclusion about the indication to END for head and neck AdCC. A more advanced UICC stage, an oropharyngeal minor salivary glands origin, and a high-grade transformation are factors to be considered in a comprehensive patient's tailored therapeutic strategy. Multicenter prospective studies are the key to finding stronger recommendations on this topic.
PubMed: 36013166
DOI: 10.3390/jcm11164924 -
Archives of Oral Biology Jan 2024This study aimed to explore the characteristics of human papillomavirus (HPV) in oropharyngeal carcinoma (OPC), in order to provide a new theoretical basis for the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to explore the characteristics of human papillomavirus (HPV) in oropharyngeal carcinoma (OPC), in order to provide a new theoretical basis for the prevention, treatment, and management of OPC.
METHODS
The electronic databases were searched available publications relevant to HPV infection and OPC. Studies were collected until July, 2023. The effect sizes were combined using R 4.2.2 software. Subgroup and sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias.
RESULTS
Seventy-one studies were included with 10,908 OPC patients. The pooled prevalence of HPV and HR-HPV infection was 44.22% and 43.94%, respectively. The genotypes of HR-HPV were HPV16 (37.24%), HPV33 (2.44%), HPV18 (1.64%), HPV35 (1.53%), and HPV58 (0.89%). The highest HPV infection was in North America (66.87%), Oceania (43.09%), and Europe (41.49%), lowest in Africa (4.89%). Females exhibited higher HPV infection (43.18% vs 34.59% in males). Top subsites of HPV infection was tonsil (45.78%), followed by base of tongue (36.66%). Infection was higher in OPC patients aged > 60 (38.15%) than < 60 (34.73%). The prevalence of HPV infection in stage I-II of OPC patients is higher than that in stage III-IV.
CONCLUSIONS
HPV genotyping (16, 18, 33, 35, 58) is a key factor in the prevention and treatment of OPC. Identifying tonsils, base of tongue, and soft palate as common subsites to improve early detection. Elderly women with high HPV infection require attention to risk management and health education for prevention.
Topics: Male; Aged; Humans; Female; Papillomavirus Infections; Human Papillomavirus Viruses; Oropharyngeal Neoplasms
PubMed: 37924712
DOI: 10.1016/j.archoralbio.2023.105830 -
The British Journal of Oral &... Jan 2020Medical practitioners' (MP) role is pivotal in primary prevention, early diagnosis, prompt referral and effective management of oral and oropharyngeal carcinomas... (Meta-Analysis)
Meta-Analysis
Medical practitioners' (MP) role is pivotal in primary prevention, early diagnosis, prompt referral and effective management of oral and oropharyngeal carcinomas (OC/OPC), which raises the importance of their effective OC/OPC education at all levels of medical education. The purpose of this systematic review was to summarise the available scientific evidence about their educational competence in dealing with OC/OPC. We made a systematic search of papers in the English language in MEDLINE, Scopus, Cochrane Library CENTRAL and CINAHL databases from their inception until December 2018. Overall, 23 cross-sectional and three interventional studies have been selected for the systematic review and 18 of these were included in the meta-analyses. Excluding tobacco use (synthesised estimate of 95% of respondents identified tobacco as an OC/OPC risk factor, 95% CI of synthesised estimate 92% to 97%) and alcohol consumption (65%, 95%CI 52% to 77%), less than half of MP (approximately) were knowledgeable about important OC/OPC risk factors including human papilloma virus (42%, 95% CI 30% to 54%), poor diet (34%, 95% CI 17% to 54%), and advancing age (45%, 95% CI 21% to 70%). There was a low to moderate level of awareness among MP regarding common precancerous oral lesions involving leukoplakia (56%, 95% CI 32% to 79%), erythroplakia (30%, 95% CI 8% to 58%), and oral lichen planus (13%, 95% CI 0 to 41%). Moderate knowledge was also recorded about frequent sites of OC development involving the tongue (48%, 95% CI 33% to 64%) and floor of the mouth (37%, 95% CI 19% to 57%). Most MP enquired about tobacco use (86%, 95% CI 74% to 96%), and alcohol consumption (73%, 95% CI 47% to 94%) during history taking, and expressed willingness to be given supplementary OC/OPC education (78%, 95% CI 54% to 96%), as well. With regard to the incidence of intraoral screening, 27% of MP (95% CI 12% to 46%) make an intraoral examination as a routine. Interestingly, studies from each continent yielded significantly different outcomes to some research questions in the review. From the MP's perspective, clinical time restrictions and deficiencies in organised training were recognised as the main barriers towards their OC/OPC educational competence. The findings of this systematic review indicated the existence of deficiencies in knowledge and misconceptions, neglected preventive responsibilities, and associated barriers towards OC/OPC. A need for improved OC/OPC training at all levels of medical education is required to increase competence worldwide.
Topics: Clinical Competence; Cross-Sectional Studies; Health Personnel; Humans; Mouth Neoplasms; Oropharyngeal Neoplasms; Referral and Consultation
PubMed: 31785865
DOI: 10.1016/j.bjoms.2019.08.007 -
Cancers May 2023Although HPV status is known to provide an improved prognosis in initial treatments of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), it is unclear how it... (Review)
Review
Although HPV status is known to provide an improved prognosis in initial treatments of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), it is unclear how it affects patients who receive salvage surgery (SS), which has historically poor survival rates. The purpose of this study was to evaluate the role of SS for patients with locoregional recurrence (LRR) of HPV-positive OPSCC and its impact survival rates. We conducted a scoping review of literature through October 2022 and included 995 individuals. Survival endpoints, such as overall survival (OS), Kaplan-Meier curves, and median post-recurrence survival, were analyzed in addition to demographics. Of all studies, 18.8% (6/32) reported any survival data for SS patients, with the most prevalent reporting 2- and 5-year OS in two studies. Median post-recurrence survival was not reported for SS. These findings reveal the limited and unpredictable reporting of survival-specific data on SS for HPV-positive OPSCC. With limited survival assessment, it is difficult to assess the potential advantages and disadvantages of this therapy to guide clinical decision-making.
PubMed: 37345169
DOI: 10.3390/cancers15102832 -
American Journal of Otolaryngology 2020Gastroesophageal reflux disease (GERD) has been associated with head and neck cancer (HNC), including laryngeal and pharyngeal anatomical sites. A systematic review and... (Meta-Analysis)
Meta-Analysis
PURPOSE
Gastroesophageal reflux disease (GERD) has been associated with head and neck cancer (HNC), including laryngeal and pharyngeal anatomical sites. A systematic review and meta-analysis was performed to examine these associations.
METHODS
Articles were retrieved from the Medline, Web of Science, Scopus, and Embase databases using keywords "gastroesophageal reflux disease", "laryngopharyngeal reflux", "head and neck cancer", and associated variants. Inclusion criteria were English language publications, human subjects, and controlled studies with described development of head and neck cancer among individuals with GERD. 13 studies with a total of 39,824 patients were included.
RESULTS
Overall, presence of GERD was associated with an increased risk of developing HNC (OR = 1.86, 95% Confidence Interval [CI] = 1.27-2.74). This association remained significant with laryngeal cancers (OR = 1.95, 95% CI = 1.33-2.86), but not pharyngeal cancers (OR = 1.56, 95% CI = 0.86-2.83). Subgroup analyses of hypopharyngeal (OR = 2.26, 95% CI = 0.67-7.68) and oropharyngeal subsites (OR = 1.39, 95% CI = 0.51-3.84) were not statistically significant. Meta-analysis of studies that objectively assessed reflux, such as pH monitor placement, showed statistical significance (OR = 2.81, 95% CI = 1.36-5.81), while studies that used subjective reporting or chart review of GERD were not significant (OR = 1.46, 95% CI = 0.89-2.40). Association between H. pylori infection and head and neck cancers was not statistically significant (OR = 2.66, 95% CI = 0.59-11.97).
CONCLUSION
A diagnosis of GERD is associated with a later diagnosis of HNC, but this association is not significant for pharyngeal cancers. Associations of GERD with HNC may be specific to laryngeal cancers.
LEVEL OF EVIDENCE
Systematic review and meta-analysis of case control studies (3a).
Topics: Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Male; Pharyngeal Neoplasms; Risk
PubMed: 32841763
DOI: 10.1016/j.amjoto.2020.102653 -
Annals of Translational Medicine Dec 2022Despite its effectiveness, the standard course of chemoradiation for the treatment of human papillomavirus (HPV)-related oropharyngeal carcinoma (OPC) results in...
BACKGROUND
Despite its effectiveness, the standard course of chemoradiation for the treatment of human papillomavirus (HPV)-related oropharyngeal carcinoma (OPC) results in considerable treatment-related adverse effects. Studies proved that HPV-positive OPC is very sensitive to radiotherapy. Using de-escalation therapy as a new strategy is critical to maintaining positive outcomes while alleviating side effects. However, some studies hold that reduced dose causes insufficient effect on tumor killing. We conducted this systematic review and meta-analysis of survival and adverse reactions in patients with HPV-related OPC by retrospective analysis and evaluated the therapeutic effect of reducing the radiation dose.
METHODS
Data were double-selected and extracted by searching seven electronic databases, Original studies in all language treated HPV-associated OPC with reduced-dose and standard-dose therapies were included. Overall survival (OS), progression-free survival (PFS), and incidence rates of adverse events were obtained by pooling analyses. Statistical analyses were performed using RStudio Version 1.1.383 (RStudio, Boston, MA, USA) via the Meta-Analysis R Package (metafor). Heterogeneity was evaluated using the I statistic and the Cochran Q test. We used Stata (version 15.0) for forest graph.
RESULTS
Thirteen studies were included in this meta-analysis, involving a dose range of 66-70 Gy for the standard treatment regimen and <66 Gy for the reduced-dose group. There was no significant difference in the age of the patients in the standard and the reduced treatment groups (60.9±5.9 . 58.6±2.4 years). Nine studies were included as standard cohort and thirteen studies were enrolled as reduced-dose cohort. The 2- and 3-year overall survival rates in the reduced-dose group (95.66% and 91.51%, respectively) were superior to those in the standard-dose group (88.36% and 87.46%, respectively). There was no significant difference in PFS between the two groups. A systematic review of articles on dose reduction and the standard dose was also conducted. The most common complication in reduced-dose radiation was oral mucositis (36.4%), followed by decreased white blood cell (WBC) count (30.5%) and dry mouth (29.1%).
CONCLUSIONS
Reducing the radiation dose in patients with HPV-related OPC substantially alleviates the treatment toxicities and optimizes the quality of life of patients while at the same time maintaining favorable oncologic outcomes.
PubMed: 36660712
DOI: 10.21037/atm-22-5935 -
Head & Neck Jan 2023The prevalence of distant metastases (DM) in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) remains unknown. A PRISMA systematic review... (Meta-Analysis)
Meta-Analysis Review
The prevalence of distant metastases (DM) in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) remains unknown. A PRISMA systematic review of DM rates in patients with HPV-related OPSCC was performed. PubMed-MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched. The primary outcome was prevalence of DM. Data on demographics, tumor classification, and clinical outcomes were also collected. Meta-analysis of pooled DM rate was determined. Ten articles met inclusion criteria, representing 1860 patients with mean follow-up of 3.6 years. Overall DM rate was 7.0% (95% CI: 5.9-8.2). T3 or T4 classification disease was associated with a 4.88-fold (95% CI: 1.92-12.40) risk of DM compared to T1 or T2 classification disease. This study is the first to systematically review the prevalence of DM among patients with HPV-related OPSCC, where pooled DM rate was found to be 7%.
Topics: Humans; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Papillomavirus Infections; Human Papillomavirus Viruses; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Papillomaviridae
PubMed: 36306202
DOI: 10.1002/hed.27230 -
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 -
Oral Oncology Jan 2024We aim to determine if there is a survival difference between patients with oropharyngeal squamous cell carcinoma (OPSCC) associated with human papillomavirus (HPV) 16... (Meta-Analysis)
Meta-Analysis
PURPOSE
We aim to determine if there is a survival difference between patients with oropharyngeal squamous cell carcinoma (OPSCC) associated with human papillomavirus (HPV) 16 versus HPV-non16 subtypes.
PATIENT AND METHODS
Databases were queried for full length, peer-reviewed, English language, articles published between 01/01/1980 and 06/08/2022. Studies reporting clinical outcomes of OPSCC associated with HPV16 and HPV-non16 subtypes with at least 10 patients were included. Primary outcome was the overall survival (OS) of patients with HPV16- versus HPV-non16-associated OPSCC. Secondary outcomes were recurrence-free survival (RFS) and pooled rate of p16 positivity by immunohistochemistry (IHC).
RESULTS
A total of 9 studies met inclusion criteria and included 1,310 patients with HPV16 and 219 with HPV-non16 subtypes of OPSCC. The prevalence of HPV-non16 was 14.3 %. The pooled 5-year OS rates for patients with HPV16 and HPV-non16 were 83.4 %(95 % CI 77.8-89.0 %) and 69.3 %(95 % CI 58.5-80.1 %), respectively. OS at 5 years was significantly worse for HPV-non16 subtype, compared to HPV16 (log odds ratio [OR] -0.54, p = 0.008). There was a trend towards worse 5-year RFS with HPV-non16 compared to HPV16 (log OR -0.55, p = 0.063). Patients with HPV-non16 disease were less likely to be p16 positive by IHC (log OR -0.91, p = 0.02).
CONCLUSION
Patients with HPV-non16OPSCC may experience worse OS and were less likely to be p16 positive compared to patients with HPV16 disease. While future prospective validation is warranted, routine assessment of both p16 IHC and HPV subtype could be considered prior to pursuing treatment de-escalation for HPV-associated OPSCC.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms; Human Papillomavirus Viruses; Carcinoma, Squamous Cell; Papillomavirus Infections; Human papillomavirus 16; Head and Neck Neoplasms; Cyclin-Dependent Kinase Inhibitor p16; Prognosis
PubMed: 38006690
DOI: 10.1016/j.oraloncology.2023.106644 -
Head & Neck Oct 2020There is a well documented racial disparity in overall survival for oropharyngeal squamous cell carcinoma (OPSCC); however, it is unknown to what extent this disparity... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is a well documented racial disparity in overall survival for oropharyngeal squamous cell carcinoma (OPSCC); however, it is unknown to what extent this disparity varies by HPV-status.
METHODS
A literature search was conducted through December 2019 using Ovid Medline, Cochrane Library, Embase, Scopus, and Clinicaltrials.gov. PRISMA guidelines were followed. A meta-analysis was conducted using random effects models to obtain pooled hazard ratios (HRs).
RESULTS
Of 649 studies initially identified, 20 studies met criteria for the narrative review. There were four studies evaluating survival by race in HPV-positive OPSCC and five studies in HPV-negative OPSCC suitable for pooling. The pooled HR associated with black race was 1.10 (95% CI 0.96-1.23) among patients with HPV-positive (n = 23 608) and 1.50 (95% CI 1.12-1.88) among patients with HPV-negative (n = 12 112). There was notable heterogeneity (I = 83%) and publication bias among the HPV-negative OPSCC studies.
CONCLUSIONS
The racial disparity in OPSCC survival persists for HPV-negative disease and is nonsignificant for HPV-positive disease. Unmeasured differences in socioeconomic status and access to care may contribute to this disparity.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck
PubMed: 32632953
DOI: 10.1002/hed.26328