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Prognostic role of lymph node micrometastasis in oral and oropharyngeal cancer: A systematic review.Oral Oncology Jul 2024An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph... (Review)
Review
BACKGROUND
An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph nodes that evade detection by standard histological evaluation of lymph node sections. Lymph node Mi and ITC could be one reason for regional recurrence after neck dissection. The aim of this study was to review the existing data regarding the impact of Mi on the survival of patients with OOSCC.
METHODS
PubMed and the Cochrane Library were searched for articles reporting the impact of Mi and ITC on patient survival. Two authors independently assessed the methodological quality of retrieved studies using the Downs and Black index. Data were also extracted on study type, number of included patients, mode of histological analysis, statistical analysis, and prognostic impact.
RESULTS
Sixteen articles with a total of 2064 patients were included in the review. Among the 16 included studies, eight revealed a statistically significant impact of Mi on at least one endpoint in the Kaplan-Meier and/or multivariate analysis. Three studies regarded Mi as Ma, while five studies found no impact of Mi on survival. Only one study demonstrated an impact of ITC on patient's prognosis in the univariate but not in the multivariate analysis.
CONCLUSION
The majority of cases included in the review were patients with oral cancer. The findings provide low-certainty evidence that Mi negatively impacts survival. Data on ITC were scarcer, so no conclusions can be drawn about their effect on survival. The lower threshold to discriminate between Mi and ITC should be defined for OOSCC since the existing thresholds are based on data from different tumors. The histological, immunohistological, and anatomical characteristics of Mi and ITC in OOSCC as well as the effect of radiotherapy on Mi should be further investigated separately for oral and oropharyngeal carcinomas.
Topics: Humans; Oropharyngeal Neoplasms; Mouth Neoplasms; Prognosis; Neoplasm Micrometastasis; Lymphatic Metastasis; Lymph Nodes; Carcinoma, Squamous Cell
PubMed: 38823172
DOI: 10.1016/j.oraloncology.2024.106808 -
PeerJ 2024To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal... (Meta-Analysis)
Meta-Analysis
Systematic evaluation and meta-analysis of the prognosis of down-staging human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma using cetuximab combined with radiotherapy instead of cisplatin combined with radiotherapy.
OBJECTIVE
To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV OPSCC).
DESIGN
Meta-analysis and systematic evaluation.
DATA SOURCES
The PubMed, Embase, Web of Science, and Cochrane library databases were searched up to June 8, 2023, as well as Clinicaltrials.gov Clinical Trials Registry, China Knowledge Network, Wanfang Data Knowledge Service Platform, and Wiprojournal.com.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomized controlled trials reporting results of standard regimens of cetuximab + radiotherapy vs cisplatin + radiotherapy in treating HPV OPSCC were included. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), local regional failure rate (LRF), distant metastasis rate (DM), and adverse events (AE).
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data.
RESULTS
A total of 874 relevant papers were obtained from the initial search, and five papers that met the inclusion criteria were included; a total of 1,617 patients with HPV OPSCC were enrolled in these studies. Meta-analysis showed that OS and PFS were significantly shorter in the cetuximab + radiotherapy group of patients with HPV OPSCC compared with those in the conventional cisplatin + radiotherapy group (HR = 2.10, 95% CI [1.39-3.15], = 0.0004; HR = 1.79, 95% CI [1.40-2.29], < 0.0001); LRF and DM were significantly increased (HR = 2.22, 95% CI [1.58-3.11], < 0.0001; HR = 1.66, 95% CI [1.07-2.58], = 0.02), but there was no significant difference in overall grade 3 to 4, acute and late AE overall (OR = 0.86, 95% CI [0.65-1.13], = 0.28).
CONCLUSIONS
Cisplatin + radiotherapy remains the standard treatment for HPV OPSCC. According to the 7th edition AJCC/UICC criteria, low-risk HPV OPSCC patients with a smoking history of ≤ 10 packs/year and non-pharyngeal tumors not involved in lymphatic metastasis had similar survival outcomes with cetuximab/cisplatin + radiotherapy. However, further clinical trials are necessary to determine whether cetuximab + radiotherapy can replace cisplatin + radiotherapy for degraded treatment in individuals who meet the aforementioned characteristics, particularly those with platinum drug allergies.
PROSPERO REGISTRATION NUMBER
CRD42023445619.
Topics: Humans; Cetuximab; Oropharyngeal Neoplasms; Cisplatin; Chemoradiotherapy; Papillomavirus Infections; Prognosis; Squamous Cell Carcinoma of Head and Neck; Neoplasm Staging; Papillomaviridae; Antineoplastic Agents, Immunological; Progression-Free Survival; Human Papillomavirus Viruses
PubMed: 38784388
DOI: 10.7717/peerj.17391 -
Acta Otorhinolaryngologica Italica :... Jun 2024Studies have demonstrated that tonsillectomy may alter the risk of oropharyngeal cancer (OPC). We systematically reviewed the evidence and pooled data to examine such an... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Studies have demonstrated that tonsillectomy may alter the risk of oropharyngeal cancer (OPC). We systematically reviewed the evidence and pooled data to examine such an association.
METHODS
PubMed, Embase, and Scopus were searched up to 25 April 2023. Studies reporting an association between tonsillectomy and oropharyngeal cancer risk at any site were included.
RESULTS
Five studies were eligible. All examined the risk of tonsillar and base of the tongue (BOT) cancer with prior history of tonsillectomy. On meta-analysis of the data, prior history of tonsillectomy was associated with a significantly decreased risk of tonsillar cancer. The second meta-analysis showed that history of tonsillectomy did not significantly alter the risk of BOT cancer. However, after exclusion of one study, the results showed an increased risk of BOT cancer with a history of tonsillectomy.
CONCLUSIONS
The scarce data available in the literature suggests that tonsillectomy may reduce the risk of tonsillar cancer but does not alter the risk of BOT cancer. Further studies are needed to explore the association between tonsillectomy and the risk of OPC.
Topics: Humans; Oropharyngeal Neoplasms; Risk Assessment; Risk Factors; Tonsillar Neoplasms; Tonsillectomy
PubMed: 38712770
DOI: 10.14639/0392-100X-N2790 -
Clinical Otolaryngology : Official... Jul 2024About 17% of patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC), which is mainly comprised of oropharyngeal SCC (OPSCC),... (Review)
Review
OBJECTIVES
About 17% of patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC), which is mainly comprised of oropharyngeal SCC (OPSCC), will experience disease recurrence, which is often considered incurable when manifested at a metastatic and/or recurrent stage. We conducted a critical qualitative systematic review. Our objectives were to provide an overview of the molecular landscape of recurrent/metastatic HPV-positive HNSCC as well as novel molecular biomarkers.
DESIGN
A literature review was conducted to identify studies reporting on the molecular characteristics of recurrent/metastatic HPV-positive HNSCC, novel molecular biomarkers and treatment options. The reviews of abstracts, full articles, and revision of the included studies, followed by data extraction and quality assessment were performed by three independent assessors. All primary literature, such as retrospective, prospective, and clinical trials as well as basic research studies were considered, and the final search was conducted at the end of February 2023. The level of evidence was rated using the guidelines published by the Oxford Centre for Evidence-based Medicine and quality was assessed using the Newcastle-Ottawa Scale criteria.
RESULTS AND CONCLUSIONS
The literature search resulted in the identification of 1991 articles. A total of 181 full articles were screened, and 66 articles were included in this analysis. Several studies reported that recurrent/metastatic HPV-positive HNSCC had higher rates of TP53 mutation and were genomically similar to HPV-negative HNSCC. The detection of circulating tumour tissue-modified HPV DNA (ctHPVDNA) as a specific biomarker has shown promising results for monitoring treatment response and recurrence in the subset of HPV-positive HNSCC. In addition, evidence for targeted therapy in recurrent/metastatic HPV-positive HNSCC has emerged, including agents that inhibit overexpressed EGFR. Studies of combination immunotherapy are also underway. Our review outlines the latest evidence on the distinct molecular profiles of recurrent/metastatic HPV-positive HNSCC as well as the clinical potential of ctHPVDNA testing in routine practice. More controlled and longitudinal studies are needed to identify additional molecular targets and to assess the performance and benefits of novel molecular biomarkers in clinical practice.
Topics: Humans; Neoplasm Recurrence, Local; Squamous Cell Carcinoma of Head and Neck; Papillomavirus Infections; Head and Neck Neoplasms; Biomarkers, Tumor; Papillomaviridae
PubMed: 38658385
DOI: 10.1111/coa.14161 -
Minerva Surgery Jun 2024Nowadays, robotic surgery finds application in the field of head and neck in the treatment of oropharyngeal tumors. The aim of this work is to examine the efficacy of...
INTRODUCTION
Nowadays, robotic surgery finds application in the field of head and neck in the treatment of oropharyngeal tumors. The aim of this work is to examine the efficacy of transoral robotic surgery (TORS) in performing safe oncological resections of oropharyngeal squamous cell carcinoma (OPSCC), with particular attention to the status of margins.
EVIDENCE ACQUISITION
Literature search of English-language studies focused on TORS through PubMed, the Cochrane Library and EMBASE databases. A total of 431 papers returned to search, but only 24 met the inclusion criteria. The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines.
EVIDENCE SYNTHESIS
Within the selected studies, the overall rate of OPSCC positive margins following TORS is minimal, especially when patient selection is adequate and when TORS is used by high volume centers.
CONCLUSIONS
TORS is a very precise and viable therapeutic tool that provides good results in terms of surgical radicality with low positive margin rates and good results in terms of overall survival and disease-free survival; however, there is still a great heterogeneity in margins definition within the available literature. Consequently, even if this surgical approach is very promising, it is still challenging to draw firm conclusions nowadays.
Topics: Humans; Oropharyngeal Neoplasms; Robotic Surgical Procedures; Margins of Excision; Carcinoma, Squamous Cell; Treatment Outcome; Disease-Free Survival
PubMed: 38618712
DOI: 10.23736/S2724-5691.24.10235-3 -
International Journal of Molecular... Mar 2024Elevated rates of human papillomavirus (HPV)-related anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) in populations like men who have sex... (Meta-Analysis)
Meta-Analysis Review
Elevated rates of human papillomavirus (HPV)-related anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) in populations like men who have sex with men (MSM) living with HIV underscore the need for effective screening. While high-resolution anoscopy-guided biopsy is the gold standard, limited provider availability poses a challenge. This has spurred interest in identifying biomarkers for improved AC prevention. Antibodies against HPV16 oncoprotein E6, known as markers for cervical and oropharyngeal cancers, are the focus of the current study. The systematic review and meta-analysis included six studies meeting inclusion criteria, assessing HPV16 E6 seroprevalence in individuals with anal HSIL or AC. A two-step meta-analysis estimated pooled odds ratios and 95% confidence intervals (CI) for HPV16 E6 seroprevalence and HSIL or AC. Pooled prevalence, sensitivity, specificity, and diagnostic odds ratios were also calculated. This meta-analysis revealed a 3.6-fold increased risk of HSIL for HPV16 E6 seropositive individuals, escalating to a 26.1-fold risk increase for AC. Pooled specificity and sensitivity indicated a high specificity (0.99; 95%CI: 0.99, 0.99) but lower sensitivity (0.19; 95%CI: 0.10, 0.34) for HPV16 E6 serostatus as an AC biomarker. In conclusion, while HPV16 E6 seroprevalence demonstrates specificity as a potential biomarker for HPV-related AC, its utility as a standalone screening tool may be limited. Instead, it could serve effectively as a confirmation test, particularly in high-risk populations, alongside other diagnostic methods. Further research is imperative to explore HPV16 E6 seroconversion dynamics and alternative screening algorithms.
Topics: Male; Humans; Homosexuality, Male; Human papillomavirus 16; Papillomavirus Infections; Early Detection of Cancer; Seroepidemiologic Studies; Sexual and Gender Minorities; Biomarkers, Tumor; Carcinoma in Situ; Anus Neoplasms; Papillomaviridae
PubMed: 38542409
DOI: 10.3390/ijms25063437 -
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 -
Acta Otorhinolaryngologica Italica :... Feb 2024The current study systematically reviews the literature about financial toxicity (FT) in head and neck cancer patients. Three databases were reviewed: PubMed, Scopus and... (Review)
Review
OBJECTIVE
The current study systematically reviews the literature about financial toxicity (FT) in head and neck cancer patients. Three databases were reviewed: PubMed, Scopus and Web of Science.
METHODS
Full text English papers published from 2000 to 2022 reporting on quantitative results about FT in head and neck cancer survivors collected through structured questionnaires or interviews were included.
RESULTS
Twenty-seven articles were included. Most of the articles were published after 2015 and from United States. There was a slight prevalence of papers dealing with oropharyngeal cancer, squamous-cell carcinoma and locally advanced head and neck cancer. Measures of FT were obtained through validated questionnaires like COST, FIT and FDQ. Collected data were mostly referrable to financial spending, financial resources, psychosocial aspect, support seeking, coping care and coping lifestyle subdomain. FT scores by COST were found to be worse in the COVID era. Financial counseling and adequate information about the costs of treatment were two effective strategies to mitigate FT.
CONCLUSIONS
FT is a relatively new challenge in head and neck cancer treatment, whose expenses are higher than therapies for other cancers. A universal method to assess FT and a unified guideline for the administration of questionnaires are needed to mitigate FT and to improve patient outcomes.
Topics: Humans; Financial Stress; Head and Neck Neoplasms; Oropharyngeal Neoplasms; Quality of Life; Surveys and Questionnaires
PubMed: 38420716
DOI: 10.14639/0392-100X-N2762 -
BMC Oral Health Feb 2024There is a blooming trend in the application of robotic surgery in oral and maxillofacial care, and different studies had evaluated the quality of life (QoL) outcomes... (Review)
Review
BACKGROUND
There is a blooming trend in the application of robotic surgery in oral and maxillofacial care, and different studies had evaluated the quality of life (QoL) outcomes among patients who underwent robotic surgery in the oral and maxillofacial region. However, empirical evidence on the QoL outcomes from these procedures is yet to be mapped. Thus, this study was conducted to evaluate the available scientific evidence and gaps concerning the QoL outcomes of patients treated with robotic surgery in the oral and maxillofacial region.
METHODS
This study adopted a scoping review design, and it was conducted and reported based on the Arksey and O'Malley, PRISMA-ScR, and AMSTAR-2 guidelines. SCOPUS, PubMed, CINAHL Complete, and APA PsycINFO were searched to retrieve relevant literature. Using Rayyan software, the retrieved literature were deduplicated, and screened based on the review's eligibility criteria. Only the eligible articles were included in the review. From the included articles, relevant data were charted, collated, and summarized.
RESULTS
A total of 123 literature were retrieved from the literature search. After deduplication and screening, only 18 heterogeneous original articles were included in the review. A total of 771 transoral robotic surgeries (TORSs) were reported in these articles, and the TORSs were conducted on patients with oropharyngeal carcinomas (OPC), recurrent tonsillitis, and obstructive sleep apnoea (OSA). In total, 20 different QoL instruments were used in these articles to assess patients' QoL outcomes, and the most used instrument was the MD Anderson Dysphagia Inventory Questionnaire (MDADI). Physical functions related to swallowing, speech and salivary functions were the most assessed QoL aspects. TORS was reported to result in improved QOL in patients with OPC, OSA, and recurrent tonsillitis, most significantly within the first postoperative year. Notably, the site of the lesion, involvement of neck dissections and the characteristics of the adjuvant therapy seemed to affect the QOL outcome in patients with OPC.
CONCLUSION
Compared to the conventional treatment modalities, TORS has demonstrated better QoL, mostly in the domains related to oral functions such as swallowing and speech, among patients treated with such. This improvement was most evident within the initial post-operative year.
Topics: Humans; Quality of Life; Robotic Surgical Procedures; Oropharyngeal Neoplasms; Tonsillitis; Sleep Apnea, Obstructive
PubMed: 38408988
DOI: 10.1186/s12903-024-04035-w -
Journal of Cancer Research and Clinical... Jan 2024Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) displays distinct epidemiological, clinical, and molecular characteristics compared to... (Review)
Review
PURPOSE
Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) displays distinct epidemiological, clinical, and molecular characteristics compared to the negative counterpart. Alterations in autophagy play an important role in cancer, and emerging evidence indicates an interplay of autophagy in HNSCC carcinogenesis and tumor promotion. However, the influence of HPV infection on autophagy in HNSCC has received less attention and has not been previously reviewed. Therefore, we here aimed to systematically review the role of autophagy explicitly in HPV HNSCC.
METHODS
Studies accessible in PubMed, Embase, Scopus, and Web of Science investigating HNSCC, highlighting the molecular biological differences between HPV and HPV HNSCC and its influences on autophagy in HNSCC were analyzed according to the PRISMA statement. A total of 10 articles were identified, included, and summarized.
RESULTS
The HPV16 E7 oncoprotein was reported to be involved in the degradation of AMBRA1 and STING, and to enhance chemotherapy-induced cell death via lethal mitophagy in HNSCC cells. Autophagy-associated gene signatures correlated with HPV-subtype and overall survival. Additionally, immunohistochemical (IHC) analyses indicate that high LC3B expression correlates with poor overall survival in oropharyngeal HNSCC patients.
CONCLUSION
HPV may dampen general bulk autophagic flux via degradation of AMBRA1 but may promote selective autophagic degradation of STING and mitochondria. Interpretations of correlations between autophagy-associated gene expressions or IHC analyses of autophagy-related (ATG) proteins in paraffin embedded tissue with clinicopathological features without biological validation need to be taken with caution.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Papillomavirus Infections; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Autophagy; Adaptor Proteins, Signal Transducing
PubMed: 38291202
DOI: 10.1007/s00432-023-05514-3