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BMC Cancer Jun 2024Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We...
BACKGROUND
Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We investigated the association between different psychosocial factors, socioeconomic status, and patient delays in T3-T4 oral, oropharyngeal, and laryngeal cancer.
PATIENTS AND METHODS
We conducted a nationwide prospective questionnaire-based study (n = 203) over a 3-year period.
RESULTS
We found no association between psychosocial factors (depression, social isolation, loneliness, and cynical hostility) and patient delay. Depression was three times more common among head and neck cancer patients compared with the general Finnish population. Head and neck cancer patients had lower educational levels and employment status, and were more often current smokers and heavy drinkers.
CONCLUSIONS
Although we found no association between patient delay and psychosocial factors, patients diagnosed with a large head and neck cancer appeared to have a lower socioeconomic status and higher risk for developing depression, which should be considered in clinical practice.
Topics: Humans; Male; Female; Laryngeal Neoplasms; Middle Aged; Oropharyngeal Neoplasms; Aged; Surveys and Questionnaires; Prospective Studies; Depression; Mouth Neoplasms; Adult; Quality of Life; Finland; Social Class; Neoplasm Staging; Socioeconomic Factors; Time-to-Treatment
PubMed: 38914952
DOI: 10.1186/s12885-024-12517-x -
Scientific Reports Jun 2024Several studies have emphasised how positive and negative human papillomavirus (HPV+ and HPV-, respectively) oropharyngeal squamous cell carcinoma (OPSCC) has...
Several studies have emphasised how positive and negative human papillomavirus (HPV+ and HPV-, respectively) oropharyngeal squamous cell carcinoma (OPSCC) has distinct molecular profiles, tumor characteristics, and disease outcomes. Different radiomics-based prediction models have been proposed, by also using innovative techniques such as Convolutional Neural Networks (CNNs). Although some of these models reached encouraging predictive performances, there evidence explaining the role of radiomic features in achieving a specific outcome is scarce. In this paper, we propose some preliminary results related to an explainable CNN-based model to predict HPV status in OPSCC patients. We extracted the Gross Tumor Volume (GTV) of pre-treatment CT images related to 499 patients (356 HPV+ and 143 HPV-) included into the OPC-Radiomics public dataset to train an end-to-end Inception-V3 CNN architecture. We also collected a multicentric dataset consisting of 92 patients (43 HPV+ , 49 HPV-), which was employed as an independent test set. Finally, we applied Gradient-weighted Class Activation Mapping (Grad-CAM) technique to highlight the most informative areas with respect to the predicted outcome. The proposed model reached an AUC value of 73.50% on the independent test. As a result of the Grad-CAM algorithm, the most informative areas related to the correctly classified HPV+ patients were located into the intratumoral area. Conversely, the most important areas referred to the tumor edges. Finally, since the proposed model provided additional information with respect to the accuracy of the classification given by the visualization of the areas of greatest interest for predictive purposes for each case examined, it could contribute to increase confidence in using computer-based predictive models in the actual clinical practice.
Topics: Humans; Oropharyngeal Neoplasms; Tomography, X-Ray Computed; Neural Networks, Computer; Papillomavirus Infections; Male; Female; Papillomaviridae; Middle Aged; Aged; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Tumor Burden; Human Papillomavirus Viruses
PubMed: 38902523
DOI: 10.1038/s41598-024-65240-9 -
Scientific Reports Jun 2024The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is primarily due to human papillomavirus, and understanding the tumor biology caused by the...
The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is primarily due to human papillomavirus, and understanding the tumor biology caused by the virus is crucial. Our goal was to investigate the proteins present in the serum of patients with OPSCC, which were not previously studied in OPSCC tissue. We examined the difference in expression of these proteins between HPV-positive and -negative tumors and their correlation with clinicopathological parameters and patient survival. The study included 157 formalin-fixed, paraffin-embedded tissue samples and clinicopathological data. Based on the protein levels in the sera of OPSCC patients, we selected 12 proteins and studied their expression in HPV-negative and HPV-positive OPSCC cell lines. LRG1, SDR16C5, PIP4K2C and MVD proteins were selected for immunohistochemical analysis in HPV-positive and -negative OPSCC tissue samples. These protein´s expression levels were compared with clinicopathological parameters and patient survival to investigate their clinical relevance. LRG1 expression was strong in HPV-negative whereas SDR16C5 expression was strong in HPV-positive tumors. Correlation was observed between LRG1, SDR16C5, and PIP4K2C expression and patient survival. High expression of PIP4K2C was found to be an independent prognostic factor for overall survival and expression correlated with HPV-positive tumor status. The data suggest the possible role of LRG1, SDR16C5 and PIP4K2C in OPSCC biology.
Topics: Humans; Male; Oropharyngeal Neoplasms; Female; Middle Aged; Aged; Papillomavirus Infections; Glycoproteins; Carcinoma, Squamous Cell; Biomarkers, Tumor; Squamous Cell Carcinoma of Head and Neck; Papillomaviridae; Adult; Prognosis; Cell Line, Tumor
PubMed: 38898137
DOI: 10.1038/s41598-024-64823-w -
Journal of Otolaryngology - Head & Neck... 2024Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with radiation-based therapy suffer from short- and long-term toxicities that affect quality of life...
A Descriptive Study of Quality of Life Following Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.
BACKGROUND
Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with radiation-based therapy suffer from short- and long-term toxicities that affect quality of life (QOL). Transoral robotic surgery (TORS) has an established role in the management of early OPSCC but adjuvant treatment is often indicated postoperatively due to the high incidence of nodal metastasis associated with advanced human papillomavirus (HPV)-related OPSCC. To overcome the need for adjuvant radiation therapy (RT), neoadjuvant chemotherapy followed by TORS and neck dissection (ND) is proposed. This study aimed to assess if QOL in HPV-associated OPSCC receiving neoadjuvant chemotherapy followed by TORS and ND returns to baseline within 12 months of completing treatment.
METHODS
A 12 month longitudinal study was carried out at McGill University Health Centre in Montreal, Canada, among a convenience sample of patients with American Joint Committee on Cancer Seventh Edition stage III and IVa HPV-related OPSCC who were treated with neoadjuvant chemotherapy followed by TORS and ND. QOL data were obtained pretreatment and at 1, 3, 6, and 12 months following treatment completion using the European Organisation for Research and Treatment of Cancer Core and Head and Neck extension modules. Paired tests and mixed models for repeated measures analysis were used to assess changes in QOL from baseline to 12 months postoperatively and over time, respectively.
RESULTS
Nineteen of 23 patients (median age 58 years) who received the study treatment fulfilled the eligibility criteria. OPSCC subsites were palatine tonsil (n = 12) and base of tongue (n = 7). All 19 patients were treated per protocol and none required adjuvant RT as per pathology review and protocol requirements at a postoperative multidisciplinary team tumor board discussion. No significant differences were found when comparing 12 month QOL follow-up scores to pretreatment scores in measures that would likely be affected by RT [eg, swallowing ( = .7), social eating ( = .8), xerostomia ( = .9)].
CONCLUSION
In HPV-related OPSCC, neoadjuvant chemotherapy followed by TORS and ND as definitive treatment is associated with excellent QOL outcomes. Postoperative QOL scores returned to baseline by 3 months and were maintained for all measures, indicating a return to normal function.
Topics: Humans; Quality of Life; Robotic Surgical Procedures; Male; Middle Aged; Female; Oropharyngeal Neoplasms; Neoadjuvant Therapy; Papillomavirus Infections; Aged; Carcinoma, Squamous Cell; Longitudinal Studies; Neck Dissection; Chemotherapy, Adjuvant; Adult; Human Papillomavirus Viruses
PubMed: 38888957
DOI: 10.1177/19160216241248670 -
Radiotherapy and Oncology : Journal of... Jun 2024Preclinical research demonstrated that the exposure of microbubbles (intravascular gas microspheres) to focussed ultrasound within the targeted tumour upregulates...
BACKGROUND AND PURPOSE
Preclinical research demonstrated that the exposure of microbubbles (intravascular gas microspheres) to focussed ultrasound within the targeted tumour upregulates pro-apoptotic pathways and enhances radiation-induced tumour cell death. This study aimed to assess the safety and efficacy of magnetic resonance (MR)-guided focussed ultrasound-stimulated microbubbles (MRgFUS-MB) for head and neck cancers (HN).
MATERIALS AND METHODS
This prospective phase 1 clinical trial included patients with newly diagnosed or recurrent HN cancer (except nasopharynx malignancies) for whom locoregional radiotherapy with radical- or palliative-intent as deemed appropriate. Patients with contraindications for microbubble administration or contrast-enhanced MR were excluded. MR-coupled focussed ultrasound sonicated intravenously administered microbubbles within the MR-guided target volume. Patients receiving 5-10 and 33-35 radiation fractions were planned for 2 and 3 MRgFUS-MB treatments, respectively. Primary endpoint was toxicity per CTCAEv5.0. Secondary endpoint was tumour response at 3 months per RECIST 1.1 criteria.
RESULTS
Twelve patients were enrolled between Jun/2020 and Nov/2023, but 1 withdrew consent. Eleven patients were included in safety analysis. Median follow-up was 7 months (range, 0.3-38). Most patients had oropharyngeal cancer (55 %) and received 20-30 Gy/5-10 fractions (63 %). No systemic toxicity or MRgFUS-MB-related adverse events occurred. The most severe acute adverse events were radiation-related grade 3 toxicities in 6 patients (55 %; dermatitis in 3, mucositis in 1, dysphagia in 6). No radiation necrosis or grade 4/5 toxicities were reported. 8 patients were included in the 3-month tumour response assessment: 4 had partial response (50 %), 3 had complete response (37.5 %), and 1 had progressive disease (12.5 %).
CONCLUSIONS
MRgFUS-MB treatment was safe and associated with high rates of tumour response at 3 months.
PubMed: 38879128
DOI: 10.1016/j.radonc.2024.110380 -
Journal For Immunotherapy of Cancer Jun 2024Oropharyngeal squamous cell carcinoma (OPSCC) induced by human papillomavirus (HPV-positive) is associated with better clinical outcomes than HPV-negative OPSCC....
BACKGROUND
Oropharyngeal squamous cell carcinoma (OPSCC) induced by human papillomavirus (HPV-positive) is associated with better clinical outcomes than HPV-negative OPSCC. However, the clinical benefits of immunotherapy in patients with HPV-positive OPSCC remain unclear.
METHODS
To identify the cellular and molecular factors that limited the benefits associated with HPV in OPSCC immunotherapy, we performed single-cell RNA (n=20) and T-cell receptor sequencing (n=10) analyses of tonsil or base of tongue tumor biopsies prior to immunotherapy. Primary findings from our single-cell analysis were confirmed through immunofluorescence experiments, and secondary validation analysis were performed via publicly available transcriptomics data sets.
RESULTS
We found significantly higher transcriptional diversity of malignant cells among non-responders to immunotherapy, regardless of HPV infection status. We also observed a significantly larger proportion of CD4 follicular helper T cells (Tfh) in HPV-positive tumors, potentially due to enhanced Tfh differentiation. Most importantly, CD8 resident memory T cells (Trm) with elevated (encoding CD161) expression showed an association with dampened antitumor activity in patients with HPV-positive OPSCC, which may explain their heterogeneous clinical outcomes. Notably, all HPV-positive patients, whose Trm presented elevated levels, showed low expression of (encoding the CD161 ligand) in B cells, which may reduce tertiary lymphoid structure activity. Immunofluorescence of HPV-positive tumors treated with immune checkpoint blockade showed an inverse correlation between the density of CD161 Trm and changes in tumor size.
CONCLUSIONS
We found that CD161 Trm counteracts clinical benefits associated with HPV in OPSCC immunotherapy. This suggests that targeted inhibition of CD161 in Trm could enhance the efficacy of immunotherapy in HPV-positive oropharyngeal cancers.
TRIAL REGISTRATION NUMBER
NCT03737968.
Topics: Humans; Oropharyngeal Neoplasms; Single-Cell Analysis; Immunotherapy; Papillomavirus Infections; Male; Female; Middle Aged; Aged; NK Cell Lectin-Like Receptor Subfamily B
PubMed: 38857913
DOI: 10.1136/jitc-2023-008667 -
Technology in Cancer Research &... 2024The purpose of this research was to compare two treatment techniques for oropharyngeal cancers: conventional linac-based static intensity-modulated radiotherapy (sIMRT)... (Comparative Study)
Comparative Study
OBJECTIVE
The purpose of this research was to compare two treatment techniques for oropharyngeal cancers: conventional linac-based static intensity-modulated radiotherapy (sIMRT) and helical tomotherapy (HT). The study examined several parameters, including target coverage, organs at risk, integral dose, and beam on time. Additionally, the study evaluated the doses to the parotid, temporomandibular joint, and pharyngeal constrictor muscles, which are important for swallowing.
METHOD
The present study retrospectively analyzed the data of 13 patients with oropharyngeal cancer who underwent radiotherapy between 2019 and 2021. The treatment plans for each patient were regenerated using both sIMRT and HT treatment planning systems with the sequential boost method. The techniques were evaluated and compared based on dose-volume histogram, homogeneity index, and conformity index parameters. The target coverage and organs at risk were statistically compared for two techniques. Additionally, the doses received by the healthy tissue volume were obtained for integral dose evaluation. The beam on time for each technique was assessed.
RESULTS
When considering planning target volume evaluation, there was no difference in D between the two techniques and sIMRT demonstrated higher D values compared to the HT. The HT technique had better results for all organs at risk, such as the parotid, temporomandibular joint, and pharyngeal constrictor muscle. As for integral dose, it has been shown that the sIMRT technique provides better protection compared to HT. In addition, the beam on time was also longer with the HT technique.
CONCLUSION
Both techniques may provide optimal target coverage for patients with oropharyngeal cancer. HT conferred notable advantages, especially with regard to critical structures implicated in swallowing, such as the parotid, temporomandibular joint, and pharyngeal constrictor muscle, in comparison to sIMRT.
Topics: Humans; Oropharyngeal Neoplasms; Parotid Gland; Radiotherapy Dosage; Organs at Risk; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Temporomandibular Joint; Male; Retrospective Studies; Pharyngeal Muscles; Female; Aged; Middle Aged
PubMed: 38841792
DOI: 10.1177/15330338241260646 -
Veterinary Journal (London, England :... Jun 2024Penile squamous cell carcinomas (SCCs) are common, potentially life-threatening neoplasms of horses. They are well-recognized to be caused by Equus caballus...
Penile squamous cell carcinomas (SCCs) are common, potentially life-threatening neoplasms of horses. They are well-recognized to be caused by Equus caballus papillomavirus (EcPV) type 2, although EcPV2 cannot be detected in all cases. A 23-year-old standardbred gelding developed multiple penile in situ and invasive SCCs that contained histological evidence of PV infection. By using both consensus and specific PCR primers, these lesions were found to contain EcPV7 DNA, but not DNA from EcPV2 or any other PV type. To determine how frequently EcPV7 is present in equine penile SCCs, specific primers were used to detect EcPV2 and EcPV7 in a series of 20 archived samples. EcPV7 was the only PV detected in one, both EcPV2 and 7 were detected in five, and only EcPV2 was detected in 14 SCCs. EcPV7 DNA was also detected in three of 10 archived oropharyngeal SCCs, although only as a co- infection with EcPV2. This is the first report of EcPV7 causing disease in horses. These results suggest EcPV7 could cause a subset of equine penile SCCs, and this is the first evidence that PV types other than EcPV2 can cause these neoplasms. The detection of EcPV7 in the oropharyngeal SCCs suggests a potential role of this PV type in the development of these SCCs. There were no clinical or histological features that differentiated lesions containing EcPV7 DNA from those containing EcPV2 DNA. If EcPV7 causes a proportion of equine penile SCCs, vaccines to prevent EcPV2 infection may not prevent all equine penile SCCs.
PubMed: 38838769
DOI: 10.1016/j.tvjl.2024.106155 -
BMC Public Health Jun 2024The prevalence of, and risk factors for, genital Human Papillomavirus (HPV) infections within the young adult population are well-established; the same is not known for... (Observational Study)
Observational Study
BACKGROUND
The prevalence of, and risk factors for, genital Human Papillomavirus (HPV) infections within the young adult population are well-established; the same is not known for oral HPV. This observational study aimed to determine oral HPV prevalence and abundance within a UK young adult population, and examine if sexual practices and established risk factors of oropharyngeal squamous cell carcinomas (OPSCCs) (such as smoking and alcohol consumption) influenced HPV prevalence.
METHODS
Convenience sampling was used to recruit a small sample of 452 UK-based young adults studying at a higher education (HE) institution to the study; the study was not powered. A highly sensitive real-time PCR HPV screening method was developed for the detection of multiple HPV subtypes from oral swabs. HPV-positive samples were subsequently screened by qPCR for viral subtypes HPV-6, HPV-11, HPV-16, HPV-18. Results were analysed by univariate and multivariate methods and stratified for gender, with lifestyle behaviour data collected via questionnaire. Socio-economic status was not captured within the questionnaire.
RESULTS
We found a high oral HPV prevalence of 22.79%, with a dominance of high-risk viral type HPV-16 (prevalence 19.12%; abundance average 1.08 × 10 copies/million cells) detected within healthy young adults. Frequent smoking (p = .05), masturbation (p = .029), and engagement in multiple sexual activities (p = .057), were found to be associated with oral HPV prevalence, and HPV-16 prevalence, whilst behaviours traditionally associated with genital HPV were not.
CONCLUSIONS
Our results strengthen the link between sexual practices and oral HPV transmission. We suggest that young adults should be considered high-risk for the contraction of oral HPV, although acknowledge that this sample of HE students may not be representative of the wider population. We show that high-risk HPV-16 is prevalent in the healthy population, as well as dominating within OPSCC; this study is one of the first to determine the dominance of oral HPV-16 prevalence and abundance within this population, presenting a clear need for greater awareness of oral HPV infections, and the risk factors for HPV-positive OPSCC within young adults.
Topics: Humans; Papillomavirus Infections; Male; Female; Risk Factors; Prevalence; Young Adult; United Kingdom; Sexual Behavior; Adult; Adolescent; Oropharyngeal Neoplasms; Papillomaviridae; Real-Time Polymerase Chain Reaction; Human Papillomavirus Viruses
PubMed: 38831431
DOI: 10.1186/s12889-024-18977-x -
Scientific Reports May 2024While associations between periodontitis and an elevated risk of cancer have been suggested, the results of existing observational studies have been inconsistent, also...
While associations between periodontitis and an elevated risk of cancer have been suggested, the results of existing observational studies have been inconsistent, also leaving room for further investigation into the underlying mechanisms. This study was designed to delve into the possible causal link between periodontitis and 20 standard cancers while concurrently identifying potential mediators. We initiated a Mendelian randomization analysis that drew from either publicly accessible or personally obtained genome-wide association study (GWAS) datasets. The inverse variance weighting (IVW) method served as our primary tool for analysis. To ensure the strength and consistency of our results, we implemented additional strategies, including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), bolstered by funnel plots. Our analysis unveiled an elevated risk of head and neck cancer concomitant with periodontitis (p = 0.041, OR 0.999, 95% CI 0.999-1.000), specifically a heightened risk of oropharyngeal cancer (p = 0.022, OR 0.999, 95% CI 0.999-1.000). As a result of probing into potential mediators, Fusobacterium nucleatum emerged as a likely intermediary in the promoting effect of periodontitis on oropharyngeal cancer (p = 0.021, OR 0.999, 95% CI 0.998-1.000). Inversely, basal cell carcinoma and endometrial cancer demonstrated an association with an increased incidence of periodontitis (basal cell carcinoma: p = 0.020, OR 0.987, 95% CI 0.976-0.998; endometrial cancer: p = 0.027, OR 0.984, 95% CI 0.970-0.998). However, periodontitis exerted no significant causal impact on the 19 other common cancers or the three subtypes of head and neck cancer. To conclude, our results support the theory that periodontitis contributes to an enhanced risk of head and neck cancer, particularly oropharyngeal cancer, with Fusobacterium nucleatum functioning as a potential intermediary.
Topics: Humans; Mendelian Randomization Analysis; Periodontitis; Oropharyngeal Neoplasms; Genome-Wide Association Study; Risk Factors; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38822160
DOI: 10.1038/s41598-024-63447-4