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Journal of Oral Pathology & Medicine :... Aug 2023Oral and/or oropharyngeal cancers account for approximately 2% of all malignancies, with variation across age groups, genders, and geographic locations. Treatments for... (Review)
Review
BACKGROUND
Oral and/or oropharyngeal cancers account for approximately 2% of all malignancies, with variation across age groups, genders, and geographic locations. Treatments for oral and/or oropharyngeal cancers usually consist of a combination of surgical excision most commonly followed by radiotherapy ± chemotherapy and/or immunotherapy/biotherapy depending on the nature of the malignancy. The significant morbidity caused by high-dose radiotherapy to the head and neck region is widely observed. Proton therapy is a promising treatment option that localises a proton beam to direct radiation at a specific target, with reduced irradiation to adjacent structures.
METHOD
The objective was to explore the toxicity associated with proton therapy for adults with oral and/or oropharyngeal cancer. Eligibility criteria included full-text articles, English articles, published between up till 7 January 2023. Databases included PubMed, Scopus, Web of Science, Embase, and Scopus.
RESULTS
The systematic search identified 345 studies and a total of 18 studies were included after two independent reviewers completed title, abstract, and full-text screening. Included studies were from four countries, and median participant age range was 53.3 to 66 years. The most commonly reported acute toxic effects included dysphagia, radiation dermatitis, oral mucositis, dysgeusia, and alopecia.
CONCLUSION
Proton therapy is an evolving cancer treatment technique that has diverse advantages over conventional radiotherapy and chemotherapy. This review provides evidence that supports that proton therapy has an improved acute toxicity profile compared to radiotherapy to treat oral and/or oropharyngeal cancer individuals.
Topics: Adult; Humans; Female; Male; Middle Aged; Aged; Proton Therapy; Oropharyngeal Neoplasms
PubMed: 36871197
DOI: 10.1111/jop.13426 -
Oral Oncology Aug 2023Matching treatment intensity to tumor biology is critical to precision oncology for head and neck squamous cell carcinoma (HNSCC) patients. We sought to identify...
OBJECTIVES
Matching treatment intensity to tumor biology is critical to precision oncology for head and neck squamous cell carcinoma (HNSCC) patients. We sought to identify biological features of tumor cell multinucleation, previously shown by us to correlate with survival in oropharyngeal (OP) SCC using a machine learning approach.
MATERIALS AND METHODS
Hematoxylin and eosin images from an institutional OPSCC cohort formed the training set (D). TCGA HNSCC patients (oral cavity, oropharynx and larynx/hypopharynx) formed the validation set (D). Deep learning models were trained in D to calculate a multinucleation index (MuNI) score. Gene set enrichment analysis (GSEA) was then used to explore correlations between MuNI and tumor biology.
RESULTS
MuNI correlated with overall survival. A multivariable nomogram that included MuNI, age, race, sex, T/N stage, and smoking status yielded a C-index of 0.65, and MuNI was prognostic of overall survival (2.25, 1.07-4.71, 0.03), independent of the other variables. High MuNI scores correlated with depletion of effector immunocyte subsets across all HNSCC sites independent of HPV and TP53 mutational status although the correlations were strongest in wild-type TP53 tumors potentially due to aberrant mitotic events and activation of DNA-repair mechanisms.
CONCLUSION
MuNI is associated with survival in HNSCC across subsites. This may be driven by an association between high levels of multinucleation and a suppressive (potentially exhausted) tumor immune microenvironment. Mechanistic studies examining the link between multinucleation and tumor immunity will be required to characterize biological drivers of multinucleation and their impact on treatment response and outcomes.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Precision Medicine; Oropharyngeal Neoplasms; Prognosis; Papillomavirus Infections; Tumor Microenvironment
PubMed: 37307602
DOI: 10.1016/j.oraloncology.2023.106459 -
Cancer Immunology, Immunotherapy : CII Dec 2023To assess the antitumor activity of neoadjuvant chemotherapy in conjunction with PD-1 inhibitors (neoadjuvant chemoimmunotherapy) among patients with oropharyngeal and...
Evaluation of neoadjuvant chemotherapy combined with PD-1 inhibitors in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma: a comparative study of antitumor activity.
PURPOSE
To assess the antitumor activity of neoadjuvant chemotherapy in conjunction with PD-1 inhibitors (neoadjuvant chemoimmunotherapy) among patients with oropharyngeal and hypopharyngeal squamous cell carcinoma (OPHSCC) and compare its efficacy with neoadjuvant chemotherapy alone.
METHODS
We conducted a retrospective analysis using data from patients diagnosed with OPHSCC and treated at the Sun Yat-sen University Cancer Center between September 2012 and August 2022. We included patients who received neoadjuvant chemotherapy alone or combined with PD-1 inhibitors. We assessed the clinical response using the Response Evaluation Criteria in Solid Tumors and evaluated progression-free survival (PFS) and overall survival (OS).
RESULTS
Preliminary results demonstrate that neoadjuvant chemoimmunotherapy exhibited robust antitumor activity in OPHSCC, with an impressive overall response rate (ORR) of 81.0%. Complete response and partial response rates were 14.9% and 65.9%, respectively. Notably, neoadjuvant chemoimmunotherapy demonstrated superior PFS and OS to neoadjuvant chemotherapy alone. The 1-year PFS rate was 80.7%, and the 2-year rate was 61.1%. Additionally, the 1-year OS rate reached 92.3%. Finally, a multivariate analysis identified the American Joint Committee on Cancer stage reduction post-treatment as a favorable predictor of PFS.
CONCLUSION
Our results underscore the promising potential of neoadjuvant chemoimmunotherapy in enhancing antitumor activity in patients with OPHSCC. The robust ORR, along with improved PFS and OS, supports the utility of this combined approach. These results pave the way for further investigations to validate and refine the application of neoadjuvant chemoimmunotherapy in this challenging clinical context.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Neoadjuvant Therapy; Immune Checkpoint Inhibitors; Retrospective Studies; Head and Neck Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37837458
DOI: 10.1007/s00262-023-03557-6 -
JAMA Otolaryngology-- Head & Neck... Nov 2023Due to lack of data from high-powered randomized clinical trials, the differences in functional and survival outcomes for patients with oropharyngeal squamous cell...
Differences in Functional and Survival Outcomes Between Patients Receiving Primary Surgery vs Chemoradiation Therapy for Treatment of T1-T2 Oropharyngeal Squamous Cell Carcinoma.
IMPORTANCE
Due to lack of data from high-powered randomized clinical trials, the differences in functional and survival outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) undergoing primary transoral robotic surgery (TORS) vs primary radiation therapy and/or chemoradiation therapy (RT/CRT) are unclear.
OBJECTIVES
To compare 5-year functional (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) and survivorship outcomes in patients with T1-T2 OPSCC receiving primary TORS vs RT/CRT.
DESIGN, SETTING, AND POPULATION
This national multicenter cohort study used data from a global health network (TriNetX) to identify differences in functional and survival outcomes among patients with OPSCC who underwent primary TORS or RT/CRT in 2002 to 2022. After propensity matching, 726 patients with OPSCC met inclusion criteria. In the TORS group, 363 (50%) patients had undergone primary surgery, and in the RT/CRT group, 363 (50%) patients had received primary RT/CRT. Data analyses were performed from December 2022 to January 2023 using the TriNetX platform.
EXPOSURE
Primary surgery with TORS or primary treatment with radiation therapy and/or chemoradiation therapy.
MAIN OUTCOMES AND MEASURES
Propensity score matching was used to balance the 2 groups. Functional outcomes were measured at 6 months, 1 year, 3 years, 5 years, and more than 5 years posttreatment and included dysphagia, gastrostomy tube dependence, and tracheostomy dependence according to standard medical codes. Five-year overall survivorship was compared between patients undergoing primary TORS vs RT/CRT.
RESULTS
Propensity score matching allowed a study sample with 2 cohorts comprising statistically similar parameters with 363 (50%) patients in each. Patients in the TORS cohort had a mean (SD) age of 68.5 (9.9) vs 68.8 (9.7) years in RT/CRT cohort; 86% and 88% were White individuals, respectively; 79% of patients were men in both cohorts. Primary TORS was associated with clinically meaningful increased risk of dysphagia at 6 months (OR, 1.37; 95% CI, 1.01-1.84) and 1 year posttreatment (OR, 1.71; 95% CI, 1.22-2.39) compared with primary RT/CRT. Patients receiving surgery were less likely to be gastrostomy tube dependent at 6 months (OR, 0.46; 95% CI, 0.21-1.00) and 5 years posttreatment (risk difference, -0.05; 95% CI, -0.07 to -0.02). Differences in overall rates of tracheostomy dependence (OR, 0.97; 95% CI, 0.51-1.82) between groups were not clinically meaningful. Patients with OPSCC, unmatched for cancer stage or human papillomavirus status, who received RT/CRT had worse 5-year overall survival than those who underwent primary surgery (70.2% vs 58.4%; hazard ratio, 0.56; 95% CI, 0.40-0.79).
CONCLUSIONS AND RELEVANCE
This national multicenter cohort study of patients undergoing primary TORS vs primary RT/CRT for T1-T2 OPSCC found that primary TORS was associated with a clinically meaningful increased risk of short-term dysphagia. Patients treated with primary RT/CRT had an increased risk of short- and long-term gastrostomy tube dependence and worse 5-year overall survival than those who underwent surgery.
Topics: Male; Humans; Aged; Female; Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms; Cohort Studies; Treatment Outcome; Deglutition Disorders; Robotic Surgical Procedures; Head and Neck Neoplasms
PubMed: 37422846
DOI: 10.1001/jamaoto.2023.1944 -
Nursing Sep 2023
Review
Topics: Humans; Nurses; Oropharyngeal Neoplasms
PubMed: 37616402
DOI: 10.1097/01.NURSE.0000978240.58702.f3 -
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 -
Head & Neck Jan 2024Still, little is known about microbial dysbiosis in oropharyngeal and laryngeal tissue as risk factor for development of local squamous cell carcinoma. The site-specific...
BACKGROUND
Still, little is known about microbial dysbiosis in oropharyngeal and laryngeal tissue as risk factor for development of local squamous cell carcinoma. The site-specific microbiota at these regions in healthy and cancer tissue and their modulation by environmental factors need to be defined.
METHODS
The local microbiota of cancer tissue and healthy controls was profiled by 16S rRNA gene amplicon sequencing and statistical analysis using 111 oropharyngeal and 72 laryngeal intraoperative swabs.
RESULTS
Oropharynx and larynx harbor distinct microbial communities. Clear effects of both smoking and cancer were seen in the oropharynx whereas effects in the larynx were minor.
CONCLUSION
The distinct microbial communities at larynx and oropharynx partially explain why the effects of cancer and smoking were distinct at those sites. Thus, the use of microbiota supposed to mirror community changes in another target location should be avoided and more studies on the actual cancerous environment are necessary.
Topics: Humans; Laryngeal Neoplasms; RNA, Ribosomal, 16S; Carcinoma, Squamous Cell; Larynx; Smoking; Oropharynx; Microbiota; Oropharyngeal Neoplasms; Head and Neck Neoplasms
PubMed: 37905455
DOI: 10.1002/hed.27562 -
International Journal of Molecular... Feb 2024Oropharyngeal squamous cell carcinoma (OPSCC), a subset of head and neck squamous cell carcinoma (HNSCC), involves the palatine tonsils, soft palate, base of tongue, and... (Review)
Review
Oropharyngeal squamous cell carcinoma (OPSCC), a subset of head and neck squamous cell carcinoma (HNSCC), involves the palatine tonsils, soft palate, base of tongue, and uvula, with the ability to spread to adjacent subsites. Personalized treatment strategies for Human Papillomavirus-associated squamous cell carcinoma of the oropharynx (HPVOPSCC) are yet to be established. In this article, we summarise our current understanding of the pathogenesis of HPVOPSCC, the intrinsic role of the immune system, current ICI clinical trials, and the potential role of small molecule immunotherapy in HPVOPSCC.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Oropharyngeal Neoplasms; Papillomavirus Infections; Immune System; Human Papillomavirus Viruses; Immunotherapy; Papillomaviridae
PubMed: 38474047
DOI: 10.3390/ijms25052798 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Sep 2023Oropharyngeal carcinoma is one of the most common malignant tumors of head and neck. In recent years, the incidence of Human papilloma virus-associated oropharyngeal... (Review)
Review
Oropharyngeal carcinoma is one of the most common malignant tumors of head and neck. In recent years, the incidence of Human papilloma virus-associated oropharyngeal squamous cell carcinoma(HPV-OPSCC) has been increasing year by year. With the advancement of minimally invasive surgical techniques, the wide application of intensity modulated radiation therapy, and the demand of patients for organ function protection and higher quality of life, the unique biological behavior and better prognosis of HPV-OPSCC have led to the exploration of a series of attenuated treatment modes. This article reviews the diagnosis and treatment status of oropharyngeal cancer and related research progress based on relevant reports.
Topics: Humans; Papillomavirus Infections; Quality of Life; Squamous Cell Carcinoma of Head and Neck; Head; Human Papillomavirus Viruses; Oropharyngeal Neoplasms; Head and Neck Neoplasms
PubMed: 37640996
DOI: 10.13201/j.issn.2096-7993.2023.09.009 -
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