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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 -
Cancer Medicine Feb 2024The aim of this systematic literature review was to provide updated information on human papillomavirus (HPV) prevalence in locally and regionally advanced (LA) and... (Review)
Review
A systematic literature review of the human papillomavirus prevalence in locally and regionally advanced and recurrent/metastatic head and neck cancers through the last decade: The "ALARM" study.
AIMS
The aim of this systematic literature review was to provide updated information on human papillomavirus (HPV) prevalence in locally and regionally advanced (LA) and recurrent/metastatic (RM) head and neck cancer (HNC) worldwide.
METHODS
Electronic searches were conducted on clinicaltrials.gov, MEDLINE/PubMed, Embase, and ASCO/ESMO journals of congresses for interventional studies (IS; Phase I-III trials) as well as MEDLINE and Embase for non-interventional studies (NIS) of LA/RM HNC published between January 01, 2010 and December 31, 2020. Criteria for study selection included: availability of HPV prevalence data for LA/RM HNC patients, patient enrollment from January 01, 2010 onward, and oropharyngeal cancer (OPC) included among HNC types. HPV prevalence per study was calculated as proportion of HPV+ over total number of enrolled patients. For overall HPV prevalence across studies, mean of reported HPV prevalence rates across studies and pooled estimate (sum of all HPV+ patients over sum of all patients enrolled) were assessed.
RESULTS
Eighty-one studies (62 IS; 19 NIS) were included, representing 9607 LA/RM HNC cases, with an overall mean (pooled) HPV prevalence of 32.6% (25.1%). HPV prevalence was 44.7% (44.0%) in LA and 24.3% (18.6%) in RM. Among 2714 LA/RM OPC patients from 52 studies with available data, mean (pooled) value was 55.8% (50.7%). The majority of data were derived from Northern America and Europe, with overall HPV prevalence of 46.0% (42.1%) and 24.7% (25.3%) across studies conducted exclusively in these geographic regions, respectively (Northern Europe: 31.9% [63.1%]). A "p16-based" assay was the most frequently reported HPV detection methodology (58.0%).
CONCLUSION
Over the last decade, at least one quarter of LA/RM HNC and half of OPC cases studied in IS and NIS were HPV+. This alarming burden is consistent with a potential implication of HPV in the pathogenesis of at least a subgroup of HNC, underscoring the relevance of HPV testing and prophylaxis to HNC prevention and management.
Topics: Humans; Head and Neck Neoplasms; Human Papillomavirus Viruses; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prevalence
PubMed: 38247106
DOI: 10.1002/cam4.6916 -
Clinical Oral Investigations Dec 2023To conduct a systematic review to determine the global prevalence of HPV in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To conduct a systematic review to determine the global prevalence of HPV in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC).
MATERIALS AND METHODS
Literature was searched through October 2022 in main databases to address the question "What is the global prevalence of Human Papillomavirus in oral and oropharyngeal cancer?" Studies had to identify HPV by PCR, ISH, or p16 immunohistochemistry to be eligible. Quality was assessed using the JBI checklist for prevalence studies. Meta-analyses were performed, and reporting followed PRISMA guidelines.
RESULTS
Sixty-five studies were included, and most of them had methodological limitations related to sampling and the HPV detection tool. The pooled prevalence of HPV-positivity was 10% (event rate = 0.1; 95% CI: 0.07, 0.13; P < 0.01; I = 88%) in the oral cavity and 42% (event rate = 0.42; 95% CI: 0.36, 0.49; P = 0.02; I2 = 97%) in oropharynx. The highest HPV prevalence in OSCC was reached by Japan, meanwhile, in OPSCC, Finland and Sweden were the most prevalent. HPV16 is the genotype most frequent with 69% in OSCC and 89% in OPSCC, being the tonsils the intraoral location more affected by HPV (63%, p < 0.01, I 76%).
CONCLUSION
The evidence points to an apparent burden in HPV-related OPSCC, mostly in North America, Northern Europe, and Oceania, especially due to the HPV16 infection suggesting different trends across continents.
CLINICAL RELEVANCE
This updated systematic review and meta-analysis provide sufficient evidence about the global HPV prevalence in OSCC and OPSCC and the most frequent HPV subtype worldwide.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Human Papillomavirus Viruses; Papillomavirus Infections; Prevalence; Mouth Neoplasms; Oropharyngeal Neoplasms; Head and Neck Neoplasms
PubMed: 38158517
DOI: 10.1007/s00784-023-05425-0 -
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 -
Oral Surgery, Oral Medicine, Oral... Feb 2024This systematic review aimed to describe the method followed during physical examination and the anatomical structures of the head and neck assessed in screening for... (Review)
Review
OBJECTIVE
This systematic review aimed to describe the method followed during physical examination and the anatomical structures of the head and neck assessed in screening for oral cancer and oral potentially malignant disorders (OPMDs).
STUDY DESIGN
An extensive literature search was carried out using MEDLINE/PubMed, EMBASE, Scopus, LILACS, Web of Science, Cochrane databases, and gray literature. The risk of bias was available in all papers included.
RESULTS
Of 9,688 records identified, 27 were included in this review, reporting data from 356,250 individuals screened and distributed across 11 countries. Most of these (n = 19) were based on 1 round of screening conducted by a dental professional or other health care workers. Most screening programs included visual inspection and palpation of the lips, oral cavity, and the most visible oropharyngeal sites, but the descriptions reported were imprecise. Additional inspection and palpation of the neck (submental, submandibular, cervical, and supraclavicular regions) to assess for the presence of swellings and any palpable neck nodes were also performed in 15 programs.
CONCLUSION
In conclusion, there was considerable heterogeneity in the method of physical examination in screening programs for oral cancer and OPMDs among the included studies.
Topics: Humans; Early Detection of Cancer; Mouth Neoplasms; Mouth Diseases; Lip Neoplasms; Physical Examination; Lip; Precancerous Conditions
PubMed: 37989648
DOI: 10.1016/j.oooo.2023.10.005 -
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 -
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 -
Biomedical Papers of the Medical... Dec 2023HPV16 status in oropharyngeal cancer (OPC) is an important prognostic factor. Its determination, based on immunistochemical analysis of p16 oncoprotein requires an... (Review)
Review
HPV16 status in oropharyngeal cancer (OPC) is an important prognostic factor. Its determination, based on immunistochemical analysis of p16 oncoprotein requires an invasive biopsy. Thus, alternative methods are being sought. Determining oral HPV16 status appears to be a promising alternative. However, it is not used routinely. This prompted us to perform a systematic literature review enabling us to evaluate the diagnostic and predictive ability of this approach. Thirty-four relevant studies were finally selected. For determination of HPV status in OPC, the calculated average sensitivity and specificity for oral sampling was 74% and 91%, respectively, with p16 tumour tissue marker being the gold standard. The method appears to be valuable in monitoring treatment response as well as the biological activity of the tumour, enabling early detection of persistent or relapsing carcinoma sufficiently long before its clinical and/or radiological manifestation. It can also contribute to identification of the primary tumour in cases of metastases of unknown origin. Last but not least, the screening HPV oral testing would help to identify individuals with persistent HPV oral infection who are at increased risk of development of OPC.
Topics: Humans; Papillomavirus Infections; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Carcinoma; Sensitivity and Specificity; Biomarkers, Tumor
PubMed: 37901925
DOI: 10.5507/bp.2023.040 -
International Journal of Cancer Mar 2024We intended to update human papillomavirus (HPV) prevalence and p16 positivity in oropharyngeal squamous cell carcinomars (SCC), and calculate HPV attributable fraction... (Meta-Analysis)
Meta-Analysis
We intended to update human papillomavirus (HPV) prevalence and p16 positivity in oropharyngeal squamous cell carcinomars (SCC), and calculate HPV attributable fraction (AF) for oropharyngeal SCC by geographic region. We searched Medline, Embase, and the Cochrane Library to identify published studies of HPV prevalence and p16 positivity alone or together in oropharyngeal SCC before December 28, 2021. Studies that reported type-specific HPV DNA prevalence using broad-spectrum PCR-based testing methods were included. We estimated pooled HPV prevalence, type-specific HPV prevalence, and p16 positivity. AF of HPV was calculated by geographic region. One hundred and thirty-four studies including 12 139 cases were included in our analysis. The pooled HPV prevalence estimate for oropharyngeal SCC was 48.1% (95% confidence interval [CI] 43.2-53.0). HPV prevalence varied significantly by geographic region, and the highest HPV prevalence in oropharyngeal SCC was noted in North America (72.6%, 95% CI 63.8-80.6). Among HPV positive cases, HPV 16 was the most common type with a prevalence of 40.2% (95% CI 35.7-44.7). The pooled p16 positivity in HPV positive and HPV16 positive oropharyngeal SCC cases was 87.2% (95% CI 81.6-91.2) and 91.7% (84.3-97.2). The highest AFs of HPV and HPV16 were noted in North America at 69.6% (95% CI 53.0-91.5) and 63.0% (48.0-82.7). [Correction added on 31 October 2023, after first online publication: the percentage symbol (%) was missing and has been added to 63.0% (48.0-82.7) in the Abstract and Conclusion.] A significant proportion of oropharyngeal SCC was attributable to HPV. HPV16 accounts for the majority of HPV positive oropharyngeal SCC cases. These findings highlight the importance of HPV vaccination in the prevention of a substantial proportion of oropharyngeal SCC cases.
Topics: Humans; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Head and Neck Neoplasms; Human papillomavirus 16; Human Papillomavirus Viruses; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck
PubMed: 37861207
DOI: 10.1002/ijc.34763 -
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