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Cancers Apr 2022This systematic review and meta-analysis aims to address whether age can be a determinant of overall survival (OS), disease-free survival (DFS), recurrence, distant... (Review)
Review
This systematic review and meta-analysis aims to address whether age can be a determinant of overall survival (OS), disease-free survival (DFS), recurrence, distant metastasis (DM) and second primary (SP) in surgically treated oral and oropharyngeal squamous cell carcinoma (OOPSCC). A total of 4981 cases and 44254 controls from 25 comparative observational studies were included in the analysis. A significantly better OS (matched subgroup analysis: OR 1.64; 95% CI 1.31-2.04, overall analysis: OR 1.48; 95% CI 1.09-2.01) was observed in young patients compared to older adults, with heterogeneity ranging from moderate to severe. Worse DFS (unmatched subgroup analysis OR 0.43; 95% CI 0.27-0.68) was observed in young patients compared to older adults with minimal to moderate heterogeneity. The frequency of recurrence (OR 1.49; 95% CI 1.10-2.02) and DM (OR 1.83; 95% CI 1.10-3.03) was significantly higher in the young patients, as found in unmatched and matched subgroup analysis, with the least heterogeneities. Young age can be considered as an independent prognostic factor for recurrence and distant metastases in OOP-SCC. Larger and methodologically robust observational studies with longer follow-up are needed to establish the definitive role of age as an independent prognostic factor on OS and DFS in OOPSCC.
PubMed: 35454794
DOI: 10.3390/cancers14081886 -
International Journal of Molecular... Nov 2022Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is... (Review)
Review
Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is currently the gold standard for oropharyngeal cancers, but is technically demanding, invasive, and expensive. This systematic review aims to review current markers that are detectable in biofluids, which offer promising non-invasive alternatives in oropharyngeal carcinomas (OPCs). A total of 174 clinical trials from the PubMed search engine in the last 5 years were identified and screened by 4 independent reviewers. From these, 38 eligible clinical trials were found and subsequently reviewed. The biomarkers involved, categorized by human papillomavirus (HPV)-status, were further divided according to molecular and cellular levels. Recent trials investigating biomarkers for both HPV-positive and HPV-negative OPCs have approaches from various levels and different biofluids including plasma, oropharyngeal swabs, and oral rinse. Promising candidates have been found to aid in detection, staging, and predicting prognosis, in addition to well-established factors including HPV-status, drinking and smoking status. These studies also emphasize the possibility of enhancing prediction results and increasing statistical significance by multivariate analyses. Liquid biopsies offer promising assistance in enhancing personalized medicine for cancer treatment, from lowering barriers towards early screening, to facilitating de-escalation of treatment. However, further research is needed, and the combination of liquid biopsies with pre-existing methods, including in vivo imaging and invasive techniques such as neck dissections, could also be explored in future trials.
Topics: Humans; Alphapapillomavirus; Papillomaviridae; Oropharyngeal Neoplasms; Biomarkers; Carcinoma
PubMed: 36430813
DOI: 10.3390/ijms232214336 -
Clinical and Translational Radiation... Mar 2022This systematic review aims to identify radiation dose-volume predictors of primary hypothyroidism after radiotherapy in patients with head and neck cancer (HNC). (Review)
Review
BACKGROUND AND PURPOSE
This systematic review aims to identify radiation dose-volume predictors of primary hypothyroidism after radiotherapy in patients with head and neck cancer (HNC).
MATERIALS AND METHODS
We performed a systematic literature search of Medline, EMBASE and Web of Science from database inception to July 1, 2021 for articles that discuss radiation dose-volume predictors of post-radiation primary hypothyroidism in patients with HNC. Data on the incidence, clinical risk factors and radiation dose-volume parameters were extracted. A meta-analysis was performed using the random-effects model to estimate the pooled odds ratio (OR) of thyroid volume as a predictor of the risk of post-radiation hypothyroidism, adjusted for thyroid radiation dosimetry.
RESULTS
Our search identified 29 observational studies involving 4,530 patients. With median follow-up durations ranging from 1.0 to 5.3 years, the average crude incidence of post-radiation primary hypothyroidism was 41.4 % (range, 10 %-57 %). Multiple radiation dose-volume parameters were associated with post-radiation primary hypothyroidism, including the thyroid mean dose (Dmean), minimum dose, V25, V30, V35, V45, V50, V30-60, VS45 and VS60. Thyroid Dmean and V50 were the most frequently proposed dosimetric predictors. The pooled adjusted OR of thyroid volume on the risk of post-radiation primary hypothyroidism was 0.89 (95 % confidence interval, 0.85-0.93; p < 0.001) per 1 cc increment.
CONCLUSION
Post-radiation primary hypothyroidism is a common late complication after radiotherapy for HNC. Minimizing inadvertent exposure of the thyroid gland to radiation is crucial to prevent this late complication. Radiation dose-volume constraints individualized for thyroid volume should be considered in HNC radiotherapy planning.
PubMed: 35128087
DOI: 10.1016/j.ctro.2022.01.001 -
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 Oct 2022This systematic review and meta-analysis aims to estimate the prevalence and prognostic impact of retropharyngeal lymph node metastases (RLNMs) in oropharyngeal squamous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review and meta-analysis aims to estimate the prevalence and prognostic impact of retropharyngeal lymph node metastases (RLNMs) in oropharyngeal squamous cell carcinoma (OPSCC).
METHODS
This meta-analysis was conducted according to PRISMA guidelines.
INCLUSION CRITERIA
studies with more than 20 patients reporting the prevalence or prognostic impact of RLNMs in OPSCC. Whenever available, data on HPV status and subsites were extracted.
RESULTS
Twenty-two articles were included. The overall prevalence of RLNMs in OPSCC was 13%, with no significant differences depending on HPV status. The highest prevalence was observed for posterior pharyngeal wall SCC (24%), followed by soft palate (17%), palatine tonsil (15%), and base of tongue (8%). RLNMs were associated with a significantly higher risk of death (HR:2.54;IC95%1.89-3.41) and progression (HR:2.44;IC95%1.80-3.30).
CONCLUSIONS
The prevalence of RLNMs in OPSCC was 13%, being higher in tumors of the posterior pharyngeal wall. RLNMs were associated with unfavorable outcomes.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Lymph Nodes; Lymphatic Metastasis; Oropharyngeal Neoplasms; Papillomavirus Infections; Prevalence; Prognosis; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck
PubMed: 35913029
DOI: 10.1002/hed.27166 -
JCO Global Oncology Mar 2024Head and neck cancer accounts for about one third of the global burden in India. Mucosal high-risk human papillomavirus (HPV) has been hypothesized as a contributory... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Head and neck cancer accounts for about one third of the global burden in India. Mucosal high-risk human papillomavirus (HPV) has been hypothesized as a contributory risk factor for head and neck cancer (HNC) but its prevalence in Indian patients is not well established. Therefore, this systematic review and meta-analysis aimed to estimate the prevalence of HPV in HNC in India and their attributable fraction by considering the biomarkers of carcinogenesis, p16, and HPV mRNA.
METHODS
A systematic literature search was done in Medline via PubMed, Embase, Scopus, ScienceDirect, ProQuest, and Cochrane to identify studies on HPV and HNC in the Indian population, published between January 1990 and October 2022. Fifty-four eligible studies were identified and relevant clinical information was collected. Meta-analysis was conducted to estimate the pooled prevalence of HPV DNA, p16INK4a, and mRNA percent positivity by random-effect logistic regression model using Metapreg, STATA 18.
RESULTS
Thirty-four high-quality studies were taken for meta-analysis. The pooled prevalence of HPV in HNC was 20% (95% CI, 12 to 32) with a high level of heterogeneity ( = 90.79%). The proportion of HPV in oropharyngeal cancer (OPC; 22% [95% CI, 13 to 34]) and laryngeal cancer (LC; 29% [95% CI, 17 to 46]) was higher than in oral cancer (OC; 16% [95% CI, 8 to 30]). The HPV-attributable fraction of OPC, considering the mRNA and p16 positivity, was 12.54% and 9.68%, respectively, almost similar to LC (11.6% and 9.57%), while it was much lower in OC (3.36% and 4%).
CONCLUSION
The HPV-attributable fraction is considerably lower for OC, suggesting a negligible causative role of HPV in OC. A significant proportion of OPC and LC are attributed to HPV; however, their exact causative role is unclear because of the presence of other known risk factors.
Topics: Humans; Human Papillomavirus Viruses; Papillomavirus Infections; DNA, Viral; Head and Neck Neoplasms; India; RNA, Messenger
PubMed: 38513185
DOI: 10.1200/GO.23.00464 -
Laryngoscope Investigative... Oct 2022To synthesize evidence for interactions of traditional oropharyngeal squamous cell carcinoma (OPSCC) risk factors-tobacco smoking and alcohol drinking-with human... (Review)
Review
OBJECTIVE
To synthesize evidence for interactions of traditional oropharyngeal squamous cell carcinoma (OPSCC) risk factors-tobacco smoking and alcohol drinking-with human papillomavirus (HPV).
DATA SOURCES
MEDLINE, Embase, Cochrane Database of Systematic Reviews, ProQuest, and Global Health were searched with no restrictions on language or publication date.
METHODS
All case-control studies assessing interactions between these factors in OPSCC were considered. Quality was assessed using the Newcastle-Ottawa Scale for case-control studies. The main outcome was the OR for developing OPSCC for the following interactions: (1) HPV and smoking, (2) HPV and alcohol drinking, and (3) HPV, alcohol drinking, and smoking. Interactions were assessed from stratified analysis (by HPV status) and/or joint effect analysis (synergy index and multiplicative index).
RESULTS
The search provided 3084 relevant studies, of which 9 were included. In the stratified analysis, the OR of developing OPSCC among smokers with HPV was less than that among smokers without HPV. A similar pattern was observed for alcohol drinking. This effect persisted among smokers and heavy alcohol drinkers with HPV compared with those without HPV. Joint effect analysis on the additive scale showed sub-additive antagonistic interactions between HPV and smoking, and between HPV and alcohol. On the multiplicative scale, sub-multiplicative interactions were found between HPV and smoking, and HPV and alcohol.
CONCLUSIONS
This meta-analysis suggests a negative directed interaction of HPV and smoking; and HPV and heavy alcohol drinking in the development of primary OPSCC on stratified analysis and joint effect analysis.
LEVEL OF EVIDENCE
3A.
PubMed: 36258880
DOI: 10.1002/lio2.877 -
Cancers Aug 2022Transoral Robotic Surgery (TORS) has become widely adopted for the surgical removal of oropharyngeal squamous cell carcinoma (OPSCC), with the most common locations... (Review)
Review
Transoral Robotic Surgery (TORS) has become widely adopted for the surgical removal of oropharyngeal squamous cell carcinoma (OPSCC), with the most common locations being in the tonsil and base of tongue (BOT). However, it is currently unknown if TORS has equal efficacy and outcomes in patients with tonsillar or BOT OPSCC. Therefore, the aim of this study was to compare the margin status and recurrence rates of tonsillar and BOT OPSCC after TORS. Per PRISMA guidelines, PubMed, Scopus, and CINAHL were systematically searched from inception to 2/28/2022. Articles including the surgical management of OPSCC with TORS that compared margin status, complications, and recurrence between tonsil and BOT were included. Meta-analyses of proportions and odds ratios were performed. A total of 28 studies were included, comprising 1769 patients with tonsillar OPSCC and 1139 patients with BOT OPSCC. HPV positivity was seen in 92.3% of tumors. BOT OPSCC had a higher rate of positive margins compared to tonsillar OPSCC (28.1% [95%CI 15.1-43.3] vs. 7.5% [95%CI 3.3-13.3]). No differences were seen in recurrence between BOT and tonsillar OPSCC (OR 1.1 [95%CI 0.8-1.5], = 0.480). In addition, no differences in postoperative hemorrhage were seen between tonsillar and BOT OPSCC (10.7% [95%CI 6.1-16.5] vs. 8.8% [95% CI 1.5-21.3]). While a higher rate of positive margins was seen in BOT OPSCC when compared to tonsil OPSCC, this did not translate to a higher recurrence rate in the BOT group. Future research on which subset of patients with BOT is more likely to have positive margins is warranted to improve the utility of TORS further.
PubMed: 35954500
DOI: 10.3390/cancers14153837 -
Cancers May 2022The aim of this study was to assess the prognostic value of tumor volume in oropharyngeal squamous cell carcinoma (OPSCC). The study was performed according to the... (Review)
Review
The aim of this study was to assess the prognostic value of tumor volume in oropharyngeal squamous cell carcinoma (OPSCC). The study was performed according to the PRISMA guidelines. A total of 1417 patients with a median age of 59.3 years (IQR 57.5−60) were included. The combined Hazard Ratios (HRs) for overall survival (OS) were 1.02 (95% CI, 0.99−1.05; p = 0.21) for primary tumor volume (pTV) and 1.01 (95% CI, 1.00−1.02; p = 0.15) for nodal tumor volume (nTV). Regarding locoregional control (LRC), the pooled HRs were 1.07 (95% CI, 0.99−1.17; p = 0.10) for pTV and 1.02 (95% CI, 1.01−1.03; p < 0.05) for nTV. Finally, the pooled HRs for disease-free survival (DFS) were 1.01 (95% CI, 1.00−1.03; p < 0.05) for pTV and 1.02 (95% CI, 1.01−1.03; p < 0.05) for nTV. In conclusion, pTV and nTV seem not to behave as reliable prognostic factors in OPSCC.
PubMed: 35626068
DOI: 10.3390/cancers14102465 -
Cancers Nov 2022Locally-advanced head and neck squamous cell carcinoma (HNSCC) is mainly defined by the presence of pathologic cervical lymph nodes (LNs) with or without extracapsular... (Review)
Review
Locally-advanced head and neck squamous cell carcinoma (HNSCC) is mainly defined by the presence of pathologic cervical lymph nodes (LNs) with or without extracapsular spread (ECS). Current radiologic criteria to classify LNs as non-pathologic, pathologic, or pathologic with ECS are primarily shape-based. However, significantly more quantitative information is contained within imaging modalities. This quantitative information could be exploited for classification of LNs in patients with locally-advanced HNSCC by means of artificial intelligence (AI). Currently, various reviews exploring the role of AI in HNSCC are available. However, reviews specifically addressing the current role of AI to classify LN in HNSCC-patients are sparse. The present work systematically reviews original articles that specifically explore the role of AI to classify LNs in locally-advanced HNSCC applying Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and the Study Quality Assessment Tool of National Institute of Health (NIH). Between 2001 and 2022, out of 69 studies a total of 13 retrospective, mainly monocentric, studies were identified. The majority of the studies included patients with oropharyngeal and oral cavity (9 and 7 of 13 studies, respectively) HNSCC. Histopathologic findings were defined as reference in 9 of 13 studies. Machine learning was applied in 13 studies, 9 of them applying deep learning. The mean number of included patients was 75 (SD ± 72; range 10-258) and of LNs was 340 (SD ± 268; range 21-791). The mean diagnostic accuracy for the training sets was 86% (SD ± 14%; range: 43-99%) and for testing sets 86% (SD ± 5%; range 76-92%). Consequently, all of the identified studies concluded AI to be a potentially promising diagnostic support tool for LN-classification in HNSCC. However, adequately powered, prospective, and randomized control trials are urgently required to further assess AI's role in LN-classification in locally-advanced HNSCC.
PubMed: 36358815
DOI: 10.3390/cancers14215397