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Cancers Dec 2020Human papillomavirus (HPV) drives tumorigenesis in a subset of oropharyngeal squamous cell carcinomas (OPSCC) and is increasing in prevalence across the world. Mounting... (Review)
Review
Human papillomavirus (HPV) drives tumorigenesis in a subset of oropharyngeal squamous cell carcinomas (OPSCC) and is increasing in prevalence across the world. Mounting evidence suggests HPV is also involved in a subset of sinonasal squamous cell carcinomas (SNSCC), yet small sample sizes and variability of HPV detection techniques in existing literature hinder definitive conclusions. A systematic review was performed by searching literature through March 29th 2020 using PubMed, Embase, and Web of Science Core Collection databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed by two authors independently. A meta-analysis was performed using the random-effects model. Sixty studies ( = 1449) were eligible for statistical analysis estimating an overall HPV prevalence of 25.5% (95% CI 20.7-31.0). When stratified by HPV detection method, prevalence with multiple substrate testing (20.5%, 95% CI 14.5-28.2) was lower than with single substrate testing (31.7%, 95% CI 23.6-41.1), highest in high-exposure anatomic subsites (nasal cavity and ethmoids) (37.6%, 95% CI 26.5-50.2) vs. low-exposure (15.1%, 95% CI 7.3-28.6) and highest in high HPV+ OPSCC prevalence geographic regions (North America) (30.9%, 95% CI 21.9-41.5) vs. low (Africa) (13.1, 95% CI 6.5-24.5)). While small sample sizes and variability in data cloud firm conclusions, here, we provide a new reference point prevalence for HPV in SNSCC along with orthogonal data supporting a causative role for virally driven tumorigenesis, including that HPV is more commonly found in sinonasal subsites with increased exposure to refluxed oropharyngeal secretions and in geographic regions where HPV+ OPSCC is more prevalent.
PubMed: 33561073
DOI: 10.3390/cancers13010045 -
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 -
Head & Neck Nov 2023The possibility of detecting circulating tumor HPV DNA (ctHPVDNA) in plasma in patients with oropharyngeal cancer has been demonstrated in several reports. However,... (Meta-Analysis)
Meta-Analysis Review
The possibility of detecting circulating tumor HPV DNA (ctHPVDNA) in plasma in patients with oropharyngeal cancer has been demonstrated in several reports. However, these data are from small cohorts and available tests for detection of ctHPVDNA are not fully validated. The aim is to evaluate sensitivity, specificity, and accuracy of ctHPVDNA by ddPCR to define its efficacy in the clinical setting for the diagnosis of HPV + OPSCC. A comprehensive search of three different databases: MEDLINE, Embase, and Cochrane Library databases. A total of 998 patients were evaluated from the 13 studies. OPSSC p16+ were 729, while controls p16- were 269. The meta-analytic study estimated the diagnostic performance of ctHPVDNA as follows: pooled sensitivity and specificity of 0.90 (95% CI: 0.82-0.94) and 0.94 (95% CI: 0.85-0.98), respectively; positive and negative likelihood ratios of 12.6 (95% CI: 4.9-32.1) and 0.05 (95% CI: 0.02-0.13), respectively. ddPCR for ctHPVDNA has good accuracy, sensitivity, and specificity for diagnosis of HPV + OPSCC. ctHPVDNA kinetic represents a great reliable opportunity to improve diagnostic and therapeutic management of cancer patients and could open new perspectives for understanding tumor biology.
Topics: Humans; Papillomavirus Infections; Circulating Tumor DNA; Papillomaviridae; Oropharyngeal Neoplasms; Human Papillomavirus Viruses; DNA, Viral; Head and Neck Neoplasms
PubMed: 37715656
DOI: 10.1002/hed.27515 -
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 -
Cancers Aug 2023High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6... (Review)
Review
High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0-5.5% for penile and 0-87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV.
PubMed: 37627099
DOI: 10.3390/cancers15164068 -
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 Jul 2023PSCC is a rare cancer, with approximately half of all cases related to HPV. While HPV and p16 IHC testing have proven their prognostic value for oropharyngeal cancer,... (Review)
Review
PSCC is a rare cancer, with approximately half of all cases related to HPV. While HPV and p16 IHC testing have proven their prognostic value for oropharyngeal cancer, this is not yet established for PSCC. The current level of evidence exploring the relation between PSCC and HPV is moderate, so we conducted a systematic review following PRISMA guidelines to evaluate the prognostic role of HPV and p16 IHC in PSCC clinical outcomes. We searched the PubMed, Embase, and Cochrane databases and identified 34 relevant studies that met our inclusion criteria. Of these, 33 were retrospective cohort studies, and one was a cross-sectional study. Nine studies reported that HPV-positive and p16-positive PSCC had better overall survival (OS) and disease-free survival (DFS). This study highlights the need for a meta-analysis to determine the role of routine HPV status or p16 staining testing as part of the initial diagnosis and staging of PSCC patients worldwide.
PubMed: 37509374
DOI: 10.3390/cancers15143713 -
Archives of Oral Biology Nov 2021To aim of this systematic review was to explore the relationship between Human papillomavirus (HPV) and epithelial-mesenchymal transition (EMT) related to the prognosis... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To aim of this systematic review was to explore the relationship between Human papillomavirus (HPV) and epithelial-mesenchymal transition (EMT) related to the prognosis of oropharyngeal squamous cell carcinoma (OPSCC).
DESIGN
For this systematic review, searches were performed in PubMed, Web of Science, Scopus, Science Direct, and Cochrane, and a random-effects model was used for meta-analysis. The presence of EMT was confirmed by the loss of E-cadherin immunoexpression and overexpression of vimentin.
RESULTS
In summary, EMT-related proteins were expressed regardless of HPV status; however, overall survival was better in HPV-positive OPSCC cases, with a 5.88 times lower death risk compared to HPV-negative patients (OR=0.17; 95%CI=0.10-0.30). Likewise, the maintenance of E-cadherin in OPSCC was associated with an 11.11 times lower risk of death due to the disease (OR=0.09; 95%CI=0.01-0.88).
CONCLUSIONS
More advanced clinical stages (III/IV) and the presence of lymph node metastases (N1-3) were common in OPSCC but were not significantly associated with HPV status.
Topics: Carcinoma, Squamous Cell; Epithelial-Mesenchymal Transition; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis; Squamous Cell Carcinoma of Head and Neck
PubMed: 34592489
DOI: 10.1016/j.archoralbio.2021.105267 -
Oral Oncology Dec 2023Transoral robotic surgery (TORS) is increasingly employed in the management of oropharyngeal cancer without adjuvant treatment. Attaining safe surgical margins is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Transoral robotic surgery (TORS) is increasingly employed in the management of oropharyngeal cancer without adjuvant treatment. Attaining safe surgical margins is paramount to preventing local recurrence (LR), but the necessary surgical margin dimension remains contentious.
METHODS
Systematic review and meta-analysis of studies reporting margin status and LR following TORS without adjuvant therapy for primary OPSCC.
RESULTS
The search identified 269 articles and 11 were selected for inclusion, with 406 patients included in the meta-analysis. Heterogeneity was noted in the definition of "close" margins. Random-effects pooled rate of positive margins was 7 % (95 % CI 0.04-0.12, I = 54 %, p = 0.02) and close margins was 7 % (95 % CI 0.02-0.27, I = 86 %, p=<0.01). The random-effects overall rate of LR was 6 % (95 % CI 0.04-0.10, I = 11 %, p = 0.35), 13 % (95 % CI 0.02-0.620, I = 0 %, p = 1.0) after a positive margin, and 3 % (95 % CI 0.03-0.24, I = 23 %, p = 0.26) after a close margin. Odds ratio (OR) for LR indicated higher risk of LR for positive compared to close margins (7.5; 95 % CI 1.31-42.91, I = 0 %, p = 0.51), and a slightly lower risk of LR between close and negative margins (2.22; 95 % CI 0.67-7.38, I = 0 %, p = 0.8). A lack of frozen-section analysis (OR 2.91, p = 0.36) and HPV-negative disease (OR 1.68, p = 0.03) were associated with an elevated risk of LR.
CONCLUSIONS
TORS as a standalone treatment is associated with low rates of LR; however, the literature is hampered by considerable heterogeneity in margin definitions. Larger multicentre studies are required to determine the precise margin cut-off required for oropharyngeal tumours managed with TORS alone.
Topics: Humans; Margins of Excision; Robotic Surgical Procedures; Combined Modality Therapy; Oropharyngeal Neoplasms; Odds Ratio; Retrospective Studies; Neoplasm Recurrence, Local
PubMed: 37951118
DOI: 10.1016/j.oraloncology.2023.106610 -
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