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1.
Math Biosci ; : 109247, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38969058

ABSTRACT

The human papillomavirus (HPV) is threatening human health as it spreads globally in varying degrees. On the other hand, the speed and scope of information transmission continues to increase, as well as the significant increase in the number of HPV-related news reports, it has never been more important to explore the role of media news coverage in the spread and control of the virus. Using a decreasing factor that captures the impact of media on the actions of people, this paper develops a model that characterizes the dynamics of HPV transmission with media impact, vaccination and recovery. We obtain global stability of equilibrium points employing geometric method, and further yield effective methods to contain the HPV pandemic by sensitivity analysis. With the center manifold theory, we show that there is a forward bifurcation when R0=1. Our study suggested that, besides controlling contact between infected and susceptible populations and improving effective vaccine coverage, a better intervention would be to strengthen media coverage. In addition, we demonstrated that contact rate and the effect of media coverage result in multiple epidemics of infection when certain conditions are met, implying that interventions need to be tailored to specific situations.

2.
PEC Innov ; 4: 100301, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38962500

ABSTRACT

Objective: HPV vaccination is recommended for children beginning at age 9 to prevent several types of cancer. Many parents turn to Facebook for health information. This study describes changes in HPV vaccine-related articles shared on Facebook amidst the COVID-19 pandemic. Methods: HPV-related articles shared on Facebook (2019-2021) were collected using Buzzsumo, a social media analytics tool and analyzed using content analysis. Articles were categorized by valence, misinformation, evidence types, persuasive tactics, and framing. We quantified these data and tested for difference by article year. Results: Of the 138 included articles, 51% had positive valence towards the vaccine and 36% had negative valence. In 2021, there was a significant increase in positive messaging (72% vs. 44% in 2019/2020; p < 0.01) and misinformation decreased from 50% in 2019 to 24% in 2021 (p = 0.04). Persuasive strategies were more common in 2019 than in later years. Conclusion: Despite decreased engagement in 2021, more positive HPV vaccine messaging was observed, although a quarter of articles still contained misinformation. Our results can inform strategies for communicating with parents about the HPV vaccine. Innovation: Our study is the first to analyze HPV-related articles linked on Facebook and to assess for differences during the pandemic.

3.
Exp Mol Pathol ; 138: 104915, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38964052

ABSTRACT

A subset of head and neck squamous cell carcinomas present solely as metastatic disease in the neck and are of unknown primary origin (SCCUP). Most primary tumors will ultimately be identified, usually in the oropharynx. In a minority of cases, the primary site remains elusive. Here, we examine the role of ancillary testing, including mutational signature analysis (MSA), to help identify likely primary sites in such cases. Twenty-two cases of SCCUP in the neck, collected over a 10-year period, were classified by morphology and viral status; including human papillomavirus (HPV) testing by p16 immunohistochemistry (IHC) and RT-qPCR, as well as Epstein-Barr virus (EBV) testing by EBER-ISH. CD5 and c-KIT (CD117) IHC was done to evaluate for possible thymic origin in all virus-negative cases. Whole exome sequencing, followed by MSA, was used to identify UV signature mutations indicative of cutaneous origin. HPV was identified in 12 of 22 tumors (54.5%), favoring an oropharyngeal origin, and closely associated with nonkeratinizing tumor morphology (Fisher's exact test; p = 0.0002). One tumor with indeterminant morphology had discordant HPV and p16 status (p16+/HPV-). All tumors were EBV-negative. Diffuse expression of CD5 and c-KIT was identified in 1 of 10 virus-negative SCCUPs (10%), suggesting a possible ectopic thymic origin rather than a metastasis. A UV mutational signature, indicating cutaneous origin, was identified in 1 of 10 (10%) virus-negative SCCUPs. A cutaneous auricular primary emerged 3 months after treatment in this patient. Primary tumors became clinically apparent in 2 others (1 hypopharynx, 1 hypopharynx/larynx). Thus, after follow-up, 6 tumors remained unclassifiable as to the possible site of origin (27%). Most SCCUPs of the neck in our series were HPV-associated and thus likely of oropharyngeal origin. UV signature mutation analysis and additional IHC for CD5 and c-KIT for possible thymic origin may aid in further classifying virus-negative unknown primaries. Close clinical inspection of hypopharyngeal mucosa may also be helpful, as a subset of primary tumors later emerged at this site.

4.
J Community Health ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965135

ABSTRACT

One subgroup of Latinos whose healthcare needs must be more thoroughly addressed is the roughly three million farmworkers pursuing seasonal agricultural work within the United States (U.S.). Latino migrant and seasonal farmworkers (MSFW) face compounded political, social, and personal contexts that complicate healthcare access. Although the human papillomavirus (HPV) vaccine prevents HPV infections and cancers, uptake among Hispanic adolescents remains suboptimal. Therefore, it is important to understand Latino MSFW's HPV knowledge, as well as barriers to and facilitators of vaccination so culturally appropriate measures can bolster vaccination. An integrative review was conducted in PubMed, Scopus, and Web of Science using key search terms. Results were evaluated for compatibility with inclusion/exclusion criteria, and selected articles were coded and evaluated via thematic analysis. Six studies of various designs were ultimately included in the review. While some Latino MSFW have baseline knowledge about HPV and the vaccine, knowledge gaps remain. Participants expressed curiosity about how the vaccine works, contents, side effects, dosing, recommended age, and information about prevented diseases. Although additional education and MSFW's receptiveness to provider's recommendations were cited as major facilitators, many barriers also need addressed. Providers must leverage MSFW's existing knowledge, provide education, and facilitate vaccination to protect farmworker families from HPV and related cancers. It must become standard practice for providers to recommend the HPV vaccine to MSFW, who are receptive to this conversation. Increasing vaccination can decrease the disproportionate burden of HPV-related cancers on patients and facilitate access to healthcare services.

5.
Cancer Genet ; 286-287: 29-34, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38971117

ABSTRACT

Few reports have analyzed the fusion genes involved in carcinogenesis in the oropharynx, where the incidence of human papillomavirus-associated tumors is relatively low. The aim of this study was to identify novel driver fusion genes in patients with oropharyngeal cancer. The study enrolled fifty-seven patients who were diagnosed with oropharyngeal carcinoma. RNA sequencing data from fresh-frozen specimens were used to identify candidate fusion genes via the JAFFA, arriba, and STAR-Fusion pipelines. Candidate fusion genes were confirmed by direct sequencing. The expression level of a candidate fusion gene was compared to that of tumors without fusion genes. Finally, filtering was performed for driver genes using the annoFuse pipeline. In addition, the VIRTUS pipeline was used to analyze the presence of human papillomavirus in the tumors. We identified 5 (8.8 %) novel potential driver in-frame fusion genes, MKNK2::MOB3A, ICMT::RPS6KA3, ATP1B3::GRK7, CSNK2A1::KIF16B, and FGFR3::MAEA, and 1 (1.8 %) known in-frame fusion gene, FGFR3::TACC3, in 57 patients with pharyngeal carcinoma. Our results suggest that sporadic fusion genes may contribute to tumorigenesis in oropharyngeal carcinomas.

6.
BMC Cancer ; 24(1): 807, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971725

ABSTRACT

BACKGROUND: In 2020, uterine cervical cancer (UCC) was the 12th most common cancer among women in France and the 4th worldwide. French health authorities wanted to increase Human Papilloma Virus (HPV) vaccination and screening rates. There were still many barriers to these measures among young women, their families, and health professionals and teachers. Between 2014 and 2019, international studies found inconsistent effects of HPV vaccination on UCC screening. In 2022, a survey was conducted among women aged 25 to 40 in the Nord-Pas-de-Calais region to assess participation 1) in HPV vaccination and its barriers, 2) in UCC screening as a function of HPV vaccination status. METHODS: Data were collected using an anonymous online questionnaire distributed by QR code in 80 general practices randomly selected in the Nord-Pas-de-Calais region between January and June 2022. Results were analyzed bivariately using the Chi2 test, multivariately when numbers allowed, and in age subgroups (sensitivity analysis). RESULTS: 407 complete questionnaires (for 602 participating women) were analyzed. In our sample, 41% of women aged 25 to 40 in the Nord-Pas-de-Calais region were vaccinated against HPV viruses in 2022. The risk factors for non-vaccination, after multivariable adjustment, were: the periods of eligibility for vaccination in the early days of French vaccination (2007-2012: odds ratio OR = 0.04 [95% CI, 0.02-0.09]; 2012-2017: OR = 0.5 [0.3-0.8]), information received from non-medical sources (OR = 0.3 [0.2-0.6]), and absence of information about vaccination (OR = 0.12 [0.05-0.27]). In our sample, 90% of women were screened for UCC. In bivariate analysis, women at risk of not being screened were those who were youngest, had been vaccinated against HPV, were not heterosexual, lived alone, had gynecological follow-up by their general practitioner, and did not have regular gynecological follow-up. Sensitivity analysis showed that the only risk factor significantly correlated with non-screening regardless of age group was lack of regular gynecological follow-up. CONCLUSIONS: Participation in HPV vaccination and UCC screening is improved by medical education and gynecological follow-up. This multicenter study, limited by the relative youth of vaccination in France, should be repeated after 2037 to assess the possible effect of vaccination on screening.


Subject(s)
Early Detection of Cancer , Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Vaccination , Humans , Female , Adult , Cross-Sectional Studies , France/epidemiology , Papillomavirus Vaccines/administration & dosage , Papillomavirus Infections/prevention & control , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/epidemiology , Early Detection of Cancer/statistics & numerical data , Vaccination/statistics & numerical data , Surveys and Questionnaires , Patient Acceptance of Health Care/statistics & numerical data
7.
Hum Pathol ; 150: 9-19, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38909709

ABSTRACT

OBJECTIVES: There is a paucity of data on North American cohorts of patients with penile squamous cell carcinoma (pSCC). Herein, we aimed to assess the sensitivity of various modalities to identify human papillomavirus (HPV) status, determine the prevalence of high-risk HPV-positivity, and evaluate the prognostic impact of relevant clinicopathologic variables. METHODS: Patients with pSCC (n = 121) consecutively treated with partial/total penectomy (2000-2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression. RESULTS: The majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV-positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2-99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV-negative compared to high-risk HPV-positive patients (HR 2.74, CI 1.12-8.23, P = 0.03). Moreover, among high-risk HPV-negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1-48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV-positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0-33.1). CONCLUSIONS: We demonstrate high-risk HPV-positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV-negative, and basaloid subtype in high-risk HPV-positive pSCC) may have prognostic value.

8.
Photodiagnosis Photodyn Ther ; 48: 104245, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38871015

ABSTRACT

BACKGROUND: Anal condyloma acuminatum (CA) is marked by its thorny treatment and high recurrence rate. Although 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrates significant efficacy and safety in treating anal CA, it does not completely prevent recurrence. This study aimed to develop and validate a nomogram model in predicting the risk of relapse in HIV-negative patients with anal CA following treatment with ALA-PDT. METHODS: A retrospective analysis was conducted on patients diagnosed with anal CA who received combined CO2 laser vaporization and ALA-PDT between January 2013 and May 2023. Patients were divided into recurrence and non-recurrence groups. A nomogram was developed based on factors showing statistical significance in multivariable logistic regression analysis. The discriminative ability and clinical utility of the nomogram were assessed via ROC curves and decision curve analysis, with internal validation performed through bootstrap resampling. RESULTS: Among the 176 patients included, 33 (18.75 %) experienced recurrence, while 143 did not. Independent predictors for recurrence included HPV types, history of anal intercourse, and the number of CO2 laser treatments received. Incorporating these predictors, the nomogram demonstrated a superior diagnostic performance (area under the curve = 0.881, 95 % CI: 0.818-0.935) and a significant net benefit in decision curve analysis. CONCLUSIONS: The nomogram accurately predicts the risk of recurrence in HIV-negative patients with anal CA following ALA-PDT. It offers a valuable tool for guiding preoperative clinical decision-making and establishing personalized treatment strategies to minimize the risk of relapse.

9.
Orbit ; : 1-10, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38913546

ABSTRACT

Primary tumors of the lacrimal sac (PTLS) are a rare subtype of ocular adnexa tumors, with potentially life-threatening clinical course. There has been growing evidence of human papilloma virus (HPV) as an etiological agent in these tumors.In this retrospective observational case series, we report three cases of PTLS. All three underwent an initial dacryocystorhinostomy revealing a tissular mass in the lacrimal sac. Histological findings were respectively epithelial papilloma, epithelial Malpighian papilloma, and undifferentiated epidermoid carcinoma. PCR evaluation identified HPV serotype 6 in the first case and 16 in the third, and high p16 expression was found in the second case.These three cases of PTLS with HPV detection complement 36 other cases identified in the literature, further incriminating HPV in the pathogenesis of these neoplasms. Ophthalmologists must remain wary of chronic lacrimal occlusion symptoms, and resort to CT scan and orbital Doppler sonography whenever first-line treatment fails.

10.
Microb Pathog ; 193: 106764, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38944216

ABSTRACT

Cervical cancer (CC) is the fourth most common cancer among female patients. The primary cause of all types of cervical cancer is human papillomavirus (HPV), which was projected to account for 5,70,000 reported cases in 2018. Two HPV strains (16 and 18) account for 70 % of cervical abnormalities and precancerous cervical cancers. CC is one of the main causes of the 17 % cancer-related death rate among Indian women between the ages of 30 and 69 is CC. The side effects of the currently approved treatments for cervical cancer could endanger the lives of women affected by the illness. Thus, probiotics may be extremely important in the management of CC. Numerous studies on probiotics and their potential for use in cancer diagnosis, prevention, and treatment have been conducted. This review describes the enhancement of the immune system, promotion of a balanced vaginal microbiome, and decreased risk of secondary infections, which have anti-inflammatory effects on the body. Probiotics have the potential to reduce inflammation, thereby adversely affecting cancer cell growth and metastasis. During the course of antibiotic therapy, they support a balanced vaginal microbiome. Oncogenic virus inactivation is possible with probiotic strains. In postmenopausal women, the use of vaginal probiotics helps lessen menopausal symptoms caused by Genitourinary Syndrome of Menopause (GSM). The antitumor effects of other medications can be enhanced by them as potential agents, because they can both promote the growth of beneficial bacteria and reduce the quantity of potentially harmful bacteria. The development of tumors and the proliferation of cancer cells may be indirectly affected by the restoration of the microbial balance. Probiotics may be able to prevent and treat cervical cancer, as they seem to have anticancer properties. To identify probiotics with anticancer qualities that can supplement and possibly even replace traditional cancer treatments, further investigation is required, including carefully planned clinical trials.

11.
Cureus ; 16(5): e60190, 2024 May.
Article in English | MEDLINE | ID: mdl-38868258

ABSTRACT

Objectives To evaluate the relationship between the presence of human papillomavirus (HPV) genotypes in oral rinse samples and periodontitis. Materials and methods This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted in 2013-2014. The primary outcome was the periodontal status, categorized as either no periodontitis or mild periodontitis (combined) versus moderate to severe periodontitis (combined). The primary variable of interest was the presence of different HPV types in oral rinse specimens. Several confounders were selected based on previous evidence that demonstrated a potential association between HPV infectivity and periodontal disease. Results The final sample included 3103 participants. HPV genotypes 6, 35, 39, 55, 59, 71, 72, and 73 showed a statistically significant association with at least one of the periodontal statuses (p-value < 0.05). The presence of any HPV genotype was highly significantly associated with periodontal status, with a p-value of <0.001. Multivariable logistic regression analysis revealed statistically significant associations of HPV 6 and HPV 16 with periodontitis, adjusted for age, gender, diabetes, smoking, race, federal poverty level, last dental visit, and education level. Conclusion Our study highlights a potential link between periodontitis and specific HPV genotypes, such as HPV 6 and HPV 16, in oral rinse specimens. This suggests a complex interplay between periodontal disease and oral HPV infections, underscoring the need for further research to address public health concerns and inform preventive and treatment strategies. Clinical relevance Identifying a link between periodontitis and specific HPV genotypes, such as HPV 6 and HPV 16, in oral rinse samples could prompt early screening and tailored treatment approaches. This underscores the importance of oral health promotion and targeted interventions to address both conditions and improve overall patient outcomes.

12.
Cureus ; 16(5): e60547, 2024 May.
Article in English | MEDLINE | ID: mdl-38887331

ABSTRACT

Objectives We aimed to examine the effectiveness of platinum-based triplet induction chemotherapy in metastatic squamous cell carcinoma of the head and neck (HNSCC) at diagnosis in terms of tumor human papillomavirus (HPV) status and the clinical relevance of circulating tumor HPV DNA (ctHPVDNA) during induction chemotherapy. Methods  Twenty-one patients were included. ctHPVDNA was longitudinally quantified using optimized digital PCR in a subset of patients. Results HPV-related HNSCC patients (N=7) had a significantly better response to induction chemotherapy than HPV-unrelated HNSCC patients (N=14) (complete or partial response rate, 100% vs. 36%, P = 0.007). Following induction chemotherapy, more HPV-related HNSCC patients than HPV-unrelated patients received radiotherapy (86% vs. 36%, P = 0.06). With a median follow-up of 26 months in surviving patients, the two-year overall survival was 86% in HPV-related HNSCC patients and 43% in HPV-unrelated HNSCC patients (P = 0.04). In two patients, ctHPVDNA levels drastically decreased after the first cycle of induction chemotherapy but turned to continuous increase after the second cycle, suggesting the acquisition of drug resistance by the end of the second cycle. Radiographic imaging after induction chemotherapy failed to identify the drug resistance. In one patient, ctHPVDNA decreased gradually but remained detectable after induction chemotherapy despite no radiographic residual disease. ctHPVDNA became undetectable during radiotherapy. Conclusion HPV-related HNSCC patients with distant metastasis at diagnosis should be treated definitively. The ctHPVDNA level reflects real-time disease activity. ctHPVDNA monitoring during induction chemotherapy could help the decision-making of the therapeutic strategy.

13.
Curr Oncol Rep ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38861124

ABSTRACT

PURPOSE OF REVIEW: Squamous cell carcinoma of the anus (SCCA) is an HPV-associated malignancy that has limited treatment options. Immunotherapy has expanded these options and here we review current and emerging immunotherapeutic approaches. RECENT FINDINGS: Multiple studies of single-agent anti-PD1/PD-L1 immunotherapy have demonstrated a modest response rate of approximately 10% to 15%. While a minority of patients (~5%) with SCCA experience durable complete responses, most advanced SCCAs are resistant to anti-PD1/PD-L1 monotherapy. Given the need for more broadly effective immunotherapies, novel strategies, such as adaptive cell therapies and therapeutic vaccination, are being explored. To reduce the recurrence risk of localized high-risk SCCA, strategies combining immunotherapy with chemoradiation are also being investigated. While a small subset of patients with SCCA have prolonged responses to PD1-directed immunotherapy, the majority do not derive clinical benefit, and new immunotherapeutic strategies are needed. Better understanding of the immune microenvironment and predictive biomarkers could accelerate therapeutic advances.

14.
Front Immunol ; 15: 1414298, 2024.
Article in English | MEDLINE | ID: mdl-38938577

ABSTRACT

Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide, with human papillomavirus (HPV) infection contributing to cancer development. Conventional therapies achieve only limited efficiency, especially in recurrent or metastatic HNSCC. As the immune landscape decisively impacts the survival of patients and treatment efficacy, this study comprehensively investigated the immunological tumor microenvironment (TME) and its association with patient outcome, with special focus on several dendritic cell (DC) and T lymphocyte subpopulations. Therefore, formalin-fixed paraffin-embedded tumor samples of 56 HNSCC patients, who have undergone resection and adjuvant radiotherapy, were analyzed by multiplex immunohistochemistry focusing on the detailed phenotypic characterization and spatial distribution of DCs, CD8+ T cells, and T-helper cell subsets in different tumor compartments. Immune cell densities and proportions were correlated with clinical characteristics of the whole HNSCC cohort and different HPV- or hypoxia-associated subcohorts. Tumor stroma was highly infiltrated by plasmacytoid DCs and T lymphocytes. Among the T-helper cells and CD8+ T cells, stromal regulatory T cells and intraepithelial exhausted CD8+ T cells expressing programmed cell death protein-1 (PD-1+) and/or lymphocyte-activation gene-3 (LAG-3+) were the predominant phenotypes, indicating an immunosuppressive TME. HPV-associated tumors showed significantly higher infiltration of type I and type II conventional DCs (cDC1, cDC2) as well as several CD8+ T cell phenotypes including exhausted, activated, and proliferating T cells. On the contrary, tumors with hypoxia-associated gene signatures exhibited reduced infiltration for these immune cells. By multivariate Cox regression, immune-related prognostic factors were identified. Patient clusters defined by high infiltration of DCs and T lymphocytes combined with HPV positivity or low hypoxia showed significantly prolonged survival. Thereby, cDC1 and CD8+ T cells emerged as independent prognostic factors for local and distant recurrence. These results might contribute to the implementation of an immune cell infiltration score predicting HNSCC patients' survival and such patient stratification might improve the design of future individualized radiochemo-(immuno)therapies.


Subject(s)
CD8-Positive T-Lymphocytes , Dendritic Cells , Head and Neck Neoplasms , Squamous Cell Carcinoma of Head and Neck , Tumor Microenvironment , Humans , Dendritic Cells/immunology , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/virology , Squamous Cell Carcinoma of Head and Neck/mortality , Male , Female , CD8-Positive T-Lymphocytes/immunology , Middle Aged , Tumor Microenvironment/immunology , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/virology , Head and Neck Neoplasms/mortality , Aged , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Prognosis , Adult , Papillomavirus Infections/immunology , Papillomavirus Infections/complications , Papillomavirus Infections/virology
15.
Front Oral Health ; 5: 1390081, 2024.
Article in English | MEDLINE | ID: mdl-38803348

ABSTRACT

Introduction: HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) shows distinct biological and clinical behaviour when compared to HPV-negative OPSCC. The overall role of the tumour microenvironment (TME) in head and neck cancer progression and metastasis has been studied intensively, but differences in HPV-negative and HPV-positive OPSCCs are less understood. Objective: To investigate the role of cancer-associated fibroblasts (CAFs) and the functional interactions of normal tonsil fibroblasts (NTFs) and OP CAFs with HPV+ and HPV- OPSCC cells and explore novel candidates in tumour-fibroblast crosstalk. Materials and methods: A retrospective cohort of 143 primary OPSCCs was characterised using HPV16/18 RNAScope assay, p16 IHC and ɑ-SMA. Four OPSCC, three NTF and 2 new OPSCC CAF cultures were used to assess the cytokine-based interactions using cytokine arrays on conditioned media (CM), followed by co-culture approaches to identify the role of individual cell types and the role of OPN (SPP1) and IL-6 in SCC/fibroblast communication. Results: HPV status was associated with better overall survival. Although ɑ-SMA expression was observed in both OPSCC subtypes, it provided survival stratification only in the HPV-positive group (Log-Rank p = 0.02). Three normal tonsillar fibroblast cultures (NTFs) were characterised by induction of myofibroblastic and senescent phenotypes with similar reactivity to our published NOF phenotype. The OPSCC-derived CAF cultures were characterised and their baseline myofibroblastic and senescence phenotypes varied. Cytokine array analysis of CM to identify novel candidates in the crosstalk between OPSCC tumour cells and NTFs/CAFs identified differences in the cytokine profiles on comparison of HPV+ and HPV- OPSCC cells. Osteopontin (OPN/SPP1) was identified, particularly in HPV-negative OPSCC cell analyses. We have demonstrated that OPN was produced by the OPSCC cells and revealed an associated upregulation of IL-6 in fibroblasts. Treatment of NTFs with rOPN showed alteration in phenotype, including increased contraction and IL-6 production. Antibody-mediated inhibition of CD44v6 attenuated the production of IL-6 by OPN in NTFs. Conclusion: This investigation with OPSCC fibroblasts provides novel insights into the role of CAFs in OPSCC mediated by IL-6 stimulated release of OPN from HPV negative OPSCC cells. The details of HPV-positive SCC cell/fibroblast cytokine crosstalk remain elusive.

16.
Vaccine X ; 18: 100492, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38737622

ABSTRACT

Background: Human papillomavirus (HPV) immunization can prevent cancers, but uptake has been incomplete (and worse with the COVID-19 pandemic). Dental clinicians already screen for oral cancers, many of which are caused by HPV, and could identify vaccination candidates, but this requires a case-finding strategy. Objective: The purpose of this study was (1) to develop and test a case-finding approach to identify patients who were candidates for HPV vaccinations, (2) to test an HPV vaccination intervention by dental professionals on vaccination uptake. Methods: Design: Prospective, non-randomized feasibility case finding study with a 4-week enrollment period and a 6 week follow up period in general dental offices.Setting: Two general and non-commercial dentistry offices in Edmonton, Alberta Canada.Subjects: Consecutive scheduled (non-emergent) patients who met the Health Canada criteria for HPV vaccination: immunocompetent males and females aged 9-45 years and those who are immunocompromised. Consent for the discussion was obtained from each subject or parent.Intervention: Scheduled dental patients meeting the inclusion criteria were flagged by a research assistant who reviewed the appointment schedule each week for 4 weeks. For these subjects, dental clinicians (dentists and dental hygienists) used our Dental Dialogue Tool to discuss HPV vaccination and answer questions. Participating patients who consented to receive the HPV vaccine were given a prescription by the attending dentist and were directed to follow-up with a local pharmacy to have the vaccine administered. Each participant that was provided with an HPV prescription was contacted after 6 weeks to identify if they received the first dose of vaccine.Outcomes: Yield of our case-finding strategy and receipt of a patient's first HPV vaccine dose during 6 weeks post vaccine prescription. Results: Our case-finding strategy assessed 656 scheduled patients over 4 weeks. From this screening,179 (a case-finding yield of 20.4 %), were candidates for HPV vaccine discussion. Forty-three of these 179 patients (24 %) were already vaccinated.. Two patients (1.1 %) did not consent to be spoken with and 134 (74.8 %) consented to the HPV vaccine discussion.. Forty-eight of 134 patients (35.8 %) of patients accepted a prescription from the dentist after speaking with the dental clinician. Ultimately, 8/48 (16 %) (patients received their first dose of the HPV vaccine by the 6 week of follow-up call. However, this is only 4.5 % (8/177) of those patients who did consent for the discussion of HPV cancers and vaccination from their dentist. Conclusion: We demonstrated that case-finding for HPV vaccine candidates in general dental offices was feasible, with a reasonable yield. While the dental dialogue tool was described as a great resource to explain the facts and answer questions, very few patients were vaccinated after 6 weeks of follow-up. Further work is necessary to sharpen the intervention, perhaps including follow-up discussions with the dental clinicians.

17.
Cureus ; 16(4): e57646, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38707008

ABSTRACT

BACKGROUND: Human papillomavirus (HPV) infection is a prevalent sexually transmitted infection globally, with significant associations with various cancers. Despite the availability of HPV vaccines, vaccination uptake remains suboptimal in many regions, including Saudi Arabia. METHODS: This cross-sectional survey-based study aimed to assess perceptions, attitudes, and barriers related to HPV vaccination among residents in different regions of Saudi Arabia. Participants were recruited using a stratified sampling method, and data were collected through a structured questionnaire administered electronically. RESULTS: A total of 600 participants were included in the study, with diverse demographic profiles observed. The largest age group was 26-35 years old, comprising 42.7% (n = 256) of the sample. The distribution of gender was approximately equal, with 54.7% (n = 328) male participants. Notable perception and knowledge about HPV were observed, with 49.7% (n = 298) reporting being very familiar. Furthermore, 85.8% (n = 515) believed that HPV could cause serious health problems, and 63.7% (n = 382) perceived the vaccine to be very effective. Positive attitudes toward HPV vaccination were prevalent, with a significant proportion expressing a willingness to recommend the vaccine to themselves (70.0%, n = 420) and their children (65.0%, n = 390). Healthcare provider recommendation emerged as a key influencing factor, with 73.8% (n = 443) citing it as influential. Despite favorable attitudes, barriers to HPV vaccination were reported, including vaccine cost (22.5%, n = 135) and lack of awareness (13.7%, n = 82). However, a substantial proportion of unvaccinated participants cited not applicable reasons (57.2%, n = 343), indicating prior vaccination. Factors associated with HPV vaccination uptake included higher education levels, with those holding a master's degree or above exhibiting higher odds of vaccination uptake (OR (odds ratio): 1.80, 95% CI (confidence interval): 1.35-2.40, p < 0.001). Age (26-35 vs. 18-25) also showed a borderline significant association (OR: 1.25, 95% CI: 0.98-1.60, p = 0.074). CONCLUSION: The study highlights the importance of understanding perceptions and barriers to HPV vaccination to inform public health policies and programs in Saudi Arabia. Addressing identified barriers, such as educational campaigns and improving access to vaccination services, is essential for enhancing HPV vaccination coverage and reducing the burden of HPV-related diseases in the region.

18.
HNO ; 2024 May 03.
Article in German | MEDLINE | ID: mdl-38700582

ABSTRACT

BACKGROUND: Patient-reported outcome (PRO) measures lead to improved quality of life in cancer patients and possibly to earlier detection of tumor recurrence. OBJECTIVE: Patient interest in complementing tumor follow-up care with apps for recording PROs was assessed using a questionnaire. MATERIALS AND METHODS: An independently created questionnaire to record the interest of tumor patients in a digitalized form of tumor follow-up care was evaluated (n = 110). RESULTS: In the study, the majority of tumor patients were interested in using an app for tumor disease. Taking age into account, the number increased even further for patients < 60 years of age, as expected. In line with this, human papillomavirus (HPV)-positive patients showed significantly greater interest (p = 0.021). CONCLUSION: The introduction of an app is supported by the majority of tumor patients. In addition to recording PROs, other applications (appointment reminders, patient files, sports/nutrition programs) could also be integrated.

19.
Head Neck Pathol ; 18(1): 36, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709462

ABSTRACT

BACKGROUND: To determine the prevalence of HR-HPV in a series of lip SCC from South African patients, using currently accepted HPV-testing methodologies and to define the clinical and histomorphologic features of HPV-associated lip SCC. METHODS: Fifty SCC of lip and 50 control cases were tested for HR-HPV using p16 and HR-HPV DNA PCR. p16-equivocal/positive and HPV DNA PCR-positive SCC were further evaluated for the expression of HPV-16 and HPV-18 mRNA transcripts using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to confirm transcriptionally active HPV. RESULTS: p16 was positive in 22% (n = 11) and equivocal in 4% (n = 2) of the SCC. One p16-positive case showed positivity for both HPV-16 DNA and HPV-16 E6/E7 mRNA transcripts (HPV prevalence rate of 2%). The HPV-positive case was non-keratinizing and occurred in an 80-year-old female. The two p16-equivocal cases were HR-HPV DNA positive and mRNA PCR negative. p16 was found to have a positive predictive value of 9%. CONCLUSION: Findings from our cohort of lip SCC suggest that HR-HPV may have an insignificant role in the pathogenesis of SCC at this site. Due to its low ppv, p16 is insufficient to establish HR-HPV infection in SCC of the lip. The combination of p16 and DNA PCR appears to correlate with the presence of transcriptionally active virus. HPV E6/E7 mRNA detection is the gold standard for identifying HR-HPV. mRNA testing is not widely available in sub-Saharan Africa due to technical and financial constraints; however, the test appears to be of great value in p16-equivocal lip SCC.


Subject(s)
Carcinoma, Squamous Cell , Lip Neoplasms , Papillomavirus Infections , Humans , Female , Papillomavirus Infections/complications , South Africa , Lip Neoplasms/virology , Lip Neoplasms/pathology , Aged , Middle Aged , Aged, 80 and over , Male , Carcinoma, Squamous Cell/virology , Carcinoma, Squamous Cell/pathology , Adult , Cohort Studies , Squamous Cell Carcinoma of Head and Neck/virology , Squamous Cell Carcinoma of Head and Neck/pathology , Human papillomavirus 16/genetics
20.
Curr Med Chem ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38721792

ABSTRACT

Over the past few decades, women have been troubled by grave diseases such as breast cancer, which are biologically and molecularly classified as hereditary diseases. Even though the risk of other cancers is relatively different and the downstream pathway of genetic mutation differs from breast cancer, the continued transformation of genes such as BRCA1 and BRCA2 leads to breast cancer malignancy. Notably at the molecular level, a parallel connection between the normal growth of breast and the progression of mammary cancer where the breast cancer stem cells play a crucial role in the advancement of mammary carcinoma. Arguably, several significant signaling pathways, for instance, ER signaling, HER2 signaling, and Wnt signaling control the typical breast development as well as breast stem cells, thereby cell proliferation, cell differentiation, and cell motility are involved. Incidentally, the Mouse Mammary Tumor Virus (MMTV) is notable among the unexplained viral components influenced by virus-corrupting mammary carcinomas. According to the genesis, MMTV proviral DNA is integrated into mammary epithelial cells, and genomic lymphoid cells during viral replication and triggers the progression of cellular oncogenesis. This overview reveals the deadliest theories on breast cancer, molecular mechanisms, and the MMTV transmission cycle. To establish prevention therapies that are both acceptable and efficacious, addressing apprehensions related to the toxicity of these interventions must be a preliminary hurdle to overcome.

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