Positive Human Papillomavirus Status Research Articles

Abstract A051: A conceptual framework for disclosure, intimacy, and sexual behaviors among Black women diagnosed with human papillomavirus

Abstract Purpose: Black women suffer disproportionately from Human papillomavirus (HPV) infection and related cancers, including greater associated post-diagnosis mortality. Little research and no frameworks, of which we are aware, have characterized the experiences of patients with a positive HPV diagnosis, including which factors contribute to disclosure of one’s HPV positive status, which has specific implications for intimacy with romantic partners, sexual behaviors, and the spread of HPV. Objective: To propose a conceptual framework regarding disclosure, intimacy with romantic partners, and sexual behaviors among Black women diagnosed with an HPV infection. Development: A working group including diverse perspectives in public health (e.g., infectious disease, women’s health, cancer health) conducted a review of eight existing public health, cancer health equity, and infectious diseases to identify frameworks relevant for our outcomes – i.e., communication about one’s disease status, partnership/relationship outcomes, and sexual health. Examples include Communication Privacy Management Theory, Politeness Theory, Objectification Theory, socioecological models, Maslow’s Hierarchy of Needs model, and models on social relationships and health, including those focused on stress processes. Framework: Our framework first characterizes HPV disclosure which is a multi-dimensional construct, representing the amount and type of information that is communicated to the partner. Multifaceted factors that contribute to disclosure include HPV knowledge, exposure to community stigma (e.g., sexual silence), self-efficacy for disclosure, and anticipated support from partner. These patient-level factors may not only contribute to disclosure, but also influence how HPV disclosure affects relationship outcomes (e.g., intimacy, sexual behaviors). Other theoretical moderators exist at multiple levels, including at the levels of the disclosure, partner, and relationship. At the level of the disclosure, the modality, amount, and type of information communicated may influence partner responsiveness and relationship outcomes (e.g., reduced intimacy, alternative sexual partners). At the partner level, knowledge of HPV, and exposure to community stigma can contribute to the partner’s response and relationship outcomes. At the relationship level, quality, values, and norms of the relationship, including trust, provision/receipt of emotional support, and communication norms, will also likely moderate the impact of disclosure on relationship outcomes. Emerging Research: This framework offers multiple venues for future cancer equity research. We will conduct participatory qualitative research to identify other relevant factors and pathways through which an HPV diagnosis may impact disclosure, intimacy, and subsequent sexual risk. We will subsequently conduct quantitative survey research to test associations and offer targets for future cancer health equity interventions. Citation Format: Barbara Williams, Kristine Zimmermann, Kathleen Kristensen, Kayla Moore, Whitney Miller, Elise Hu, Jamison Merrill, Marjorie Kersten, Lindsay Prescod, Uchechi Mitchell, Yamilé Molina. A conceptual framework for disclosure, intimacy, and sexual behaviors among Black women diagnosed with human papillomavirus [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A051.

Altered mitochondrial DNA copy number in cervical exfoliated cells among high‑risk HPV‑positive and HPV‑negative women.

The majority of cervical cancer cases are due to human papillomavirus (HPV) infection. However, certain cases of cervical cancer are not caused by HPV. Recent studies have shown a link between altered mitochondrial DNA (mtDNA) copy number, an indicative measure of mitochondrial dysfunction, and cervical cancer in women who test positive for HPV. However, the role of the mtDNA copy number in HPV-negative cervical cancer has remained elusive. In the present study, the mtDNA copy number was determined using quantitative PCR as the ratio between mtDNA and nuclear DNA in 287 ThinPrep cervical samples, including 143 cases with cervical abnormalities and 144 control subjects with high-risk (hr)-HPV positive or HPV-negative status. In an overall analysis of cases categorized based on the cytology diagnosis into squamous cervical carcinoma/high-grade squamous intraepithelial lesions (SCC/HSIL), low-grade squamous intraepithelial lesions (LSIL) and normal controls, the mtDNA copy number was significantly higher in all cases compared to the controls and a higher mtDNA copy number was observed in SCC/HSIL compared to LSIL cases. In the stratification analyses based on hr-HPV positive and HPV-negative status, an increased mtDNA copy number was observed in the cases compared with the controls regardless of their HPV status (P<0.05). When cases with cervical abnormalities were categorized based on histological diagnosis into cervical intraepithelial neoplasia (CIN)2/CIN3 and CIN1, an overall analysis indicated an increased mtDNA copy number in CIN2/CIN3 compared to CIN1 (P=0.01). Stratification analyses of these cases based on HPV status revealed a higher mtDNA copy number in CIN2/CIN3 compared to CIN1 regardless of HPV infection (P<0.05). These results showed that an elevated mtDNA copy number in subjects with cervical abnormalities was not influenced by the HPV status and suggested the possibility of its role in the progression of cervical cancer. The increased mtDNA copy number may be an adaptive response mechanism to compensate for mtDNA oxidative stress and energy deficiency, possibly induced by HPV infection and other environmental exposures.

Real-world study of patients with locally advanced HNSCC in the community oncology setting.

There is a need to understand the current treatment landscape for LA HNSCC in the real-world setting. This retrospective study assessed real-world outcomes and treatment patterns of 1,158 adult patients diagnosed with locally advanced (stage III-IVB) HNSCC initiating chemoradiotherapy (CRT) within the period January 2015 to December 2017 in a large network of US community oncology practices. Structured data were abstracted from electronic health records. Demographic, clinical and treatment characteristics were analyzed descriptively overall and stratified by index treatment (cisplatin + radiotherapy [RT], cisplatin + other chemotherapy + RT, or cetuximab + RT). Time to next treatment (TTNT) and overall survival (OS) were measured using the Kaplan-Meier method, and median duration of treatment was assessed. OS was compared across treatment cohorts using multinomial logistic regression with inverse probability treatment weighting. To identify covariates associated with OS, a multivariable adjusted Cox proportional hazard model was used. This study examined 22,782 records, of which 2124 had stage III to stage IVB and no other cancers, and 1158 met all eligibility criteria. Among the treatment cohorts analyzed (cisplatin + RT, cisplatin + other chemotherapy + RT, or cetuximab + RT), cisplatin + RT was the most common concurrent chemotherapy (65.8%). Among 1158 patients, 838 (72.4%) did not initiate subsequent treatment and 139 (12.0%) died. The median TTNT and median OS were only reached by the cetuximab + RT cohort. Among patients with oropharynx primary tumor location, patients with human papilloma virus (HPV) positive status had the longest time on treatment and highest survival at 60 months. Covariates associated with improved survival were never/former tobacco use, HPV positive status, and overweight or obese body mass index. Covariates associated with poorer survival were age of 60+ years, primary tumor location of hypopharynx or oral cavity and Eastern Cooperative Oncology Group performance status score of 2+. These data describe real-world treatment patterns in locally advanced head and neck squamous cell cancer and sets the baseline to assess outcomes for future studies on the community oncology population.

Role of Physiotherapy in HPV Proven Cases of Oral Submucous Fibrosis.

To assess the role of physiotherapy in human papillomavirus (HPV) proven cases of oral submucous fibrosis (OSMF). Overall, 100 patients got recruited. Only histopathologic confirmed cases of OSMF were enrolled. Purified DNA of tissue blocks was quantified by spectrophotometry. Prevalence of HPV was evaluated. The participants got randomized into 2 cohorts: HPV positive cases and HPV negative cases. Physiotherapy was done and outcome was done and outcome was assessed and compared. Assessment of results was done by SPSS software followed by statistical evaluation. HPV was seen in 80% of the patients. Mean mouth opening pretreatment and postphysiotherapy among patients with HPV positive status was 26.31 mm and 30.12 mm, respectively. Mean mouth opening pretreatment and postphysiotherapy among patients with HPV negative status was 25.11 mm and 29.74 mm, respectively. Nonsignificant results were obtained while comparing the outcome of physiotherapy among HPV positive and negative groups. Outcome of physiotherapy among OSMF patients is independent of HPV status.

Programmed death-ligand 1 and p53 as a biomarker in predicting oropharyngeal squamous cell carcinoma

Introduction. Currently, the pathogenetic role of the human papillomavirus (HPV) in carcinogenesis is well studied, that most cases of oropharyngeal squamous cell carcinoma are associated with the persistence of this infection. In addition to HPV infection, the involvement of programmed death-ligand 1 (PD-L1) and p53 proteins in the initiation and progression of oropharyngeal squamous cell carcinoma provides their formation as additional biomarkers in predicting the disease.Aim. To study the prognostic role of PD-L1 and p53 expression in oropharyngeal squamous cell carcinoma depending on HPV status.Materials and methods. The study included 62 patients with oropharyngeal squamous cell carcinoma T1–4N0–3M0 (Tumor, Nodus and Metastasis, (TNM), 7th edition) treated in 2015–2020 at the Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology and in the Tashkent and Samarkand city branches. All patients underwent immunohistochemical analysis for the presence of p16INK4a, PD-L1 and p53 protein expression in formalin-fixed and paraffin-embedded tumor tissue samples.Results. Based on the results of the assessment, it was found that positive HPV status, low and medium levels of PD-L1 expression and positive regulation of wild-type p53 are associated with favorable outcomes in patients with oropharyngeal squamous cell carcinoma. Negative HPV status, high and very high levels of PD-L1 expression, loss of wild type p53 function with upregulation of p53 mutant type leads to worse disease outcomes.Conclusion. Thus, the assessment of the expression of the onco-suppressor protein p53 helps to determine the biology of cancer cells in patients with oropharyngeal squamous cell carcinoma and suggest sensitivity to ongoing therapy, and by studying the regulation of the PD-L1 protein, antitumor immune regulation can be suggested in these patients.

Association of pretreatment lymphocyte-monocyte ratio with survival outcome in patients with head and neck cancer treated with chemoradiation.

6052 Background: Lymphocyte-monocyte ratio (LMR) from peripheral blood has been suggested as a biomarker to assess the extent of inflammation in several solid malignancies. However, the role of LMR as a prognostic factor in head and neck cancer (HNC) was unclear in several meta-analyses, and there is a paucity of literature including patients in North America. We performed an observational cohort study to evaluate the association of pre-radiation LMR with survival outcomes in North American patients with HNC. Methods: A single-institution database was queried for patients with non-metastatic HNC who underwent curative-intent definitive chemoradiation from 6/2007 to 4/2021 at the Roswell Park Comprehensive Cancer Center. Patients were excluded if they underwent induction chemotherapy or postoperative radiation. Primary endpoints were overall survival (OS) and cancer-specific survival (CSS). The association of LMR with OS and CSS was examined using nonlinear Cox proportional hazard model using restricted cubic splines (RCS), Cox multivariable analysis (MVA), and Kaplan-Meier method. LMR was stratified into high and low based on its median. Logistic MVA was performed to identify variables associated with low LMR. Propensity scored matching was used to reduce selection bias. Subgroup analyses were performed among those with available human papillomavirus (HPV) status. Results: A total of 476 patients (391 male [82.1%], median [interquartile range] age, 61 [55-67] years) met our criteria. Median follow up was 45.3 months (interquartile range 22.8-74.0). The nonlinear Cox regression model using RCS showed that low LMR was associated with worse OS and CSS in a continuous fashion without plateau and crossed the hazard ratio of 1 at LMR 3.4 for both OS and CSS. On Cox MVA, higher LMR as a continuous variable was associated with improved OS (adjusted hazard ratio [aHR] 0.90, 95% confidence interval [CI] 0.82-1.00, p = 0.04) and CSS (aHR 0.81, 95% CI 0.70-0.94, p = 0.005). The median value of LMR was 3.8. On logistic MVA, patients with other racial background (adjusted odds ratio [aOR] 0.85, 95% CI 0.74-0.97, p = 0.02) and positive HPV status (aOR 0.82, 95% CI 0.72-0.94, p = 0.005) were less likely to have low LMR. Higher T staging was associated with low LMR (aOR 1.15, 95% CI 1.04-1.27, p = 0.005). A total of 186 pairs were matched with well balanced baseline characteristics. LMR lower than 3.8 remained associated with worse OS (HR 1.60, 95% CI 1.13-2.28, p = 0.009) and CSS (HR 1.69, 95% CI 1.07-2.67, p = 0.03). In the subgroup of 319 patients (67.0%) with available HPV data, LMR status was not associated with both OS and CSS regardless of HPV status. Conclusions: Low LMR was associated with worse OS and CSS. Low LMR was also associated with higher T staging, negative HPV status, and White race. Further studies are warranted to evaluate the role of such prognostic marker to tailor interventions.

Incidence, trends, and survival of oropharyngeal squamous cell cancer in Aotearoa New Zealand, 2006–2020

BackgroundAn increasing trend of oropharyngeal cancer (OPC) has been reported in several countries with different demographic characteristics, and often attributed to increases in human papillomavirus (HPV) infection. The survival of patients with OPC has steadily improved, especially for those with positive HPV status. This study assessed the incidence, trends, and survival of OPC in Aotearoa New Zealand (NZ) by age at diagnosis, sex and ethnicity. MethodsThe study included all 2109 patients resident in NZ with a primary diagnosis of oropharyngeal squamous cell carcinoma from 2006 to 2020, identified from the National Cancer Registry. We assessed age-standardised incidence rate (ASR), annual percent change (APC) and overall and relative survival rates. ResultsThe average annual incidence of OPC was 2.2 per 100,000 population. There was a steady increase of 4.9% per year over 15 years. Although the incidence rates were higher in males over the study period, the overall rate of increase was similar in males (4.9%) and in females (4.3%). The incidence was highest in the 50–69-year group (8.8/100,000 population). This age group had an incidence that increased by 7.5% per year to 2018, and then declined. The main increase in rates was seen between the birth cohort of 1946–50 and that of 1956–60. The increase in incidence was seen in Māori and Pākehā/European populations, but no increase was seen in Pacific or Asian populations. The 5-year overall relative survival rate improved from 69% in 2006‐13 to 78% in 2014–20. Survival rates were lower in older patients, females, and Māori patients. ConclusionThis study confirmed a substantial increase in OPC incidence in NZ, with some evidence to suggest a recent slowing in this increase. Māori and Pākehā/European had the highest incidence, while Pacific and Asian populations showed the lowest rates and no increase over the study period. Survival rates have improved over time, but remained lower in some demographic groups.

MP30-20 HUMAN PAPILLOMAVIRUS SEMINAL CARRIAGE, SPERMOGRAM ABNORMALITIES AND MALE INFERTILY: A FRENCH COHORT STUDY

You have accessJournal of UrologyCME1 Apr 2023MP30-20 HUMAN PAPILLOMAVIRUS SEMINAL CARRIAGE, SPERMOGRAM ABNORMALITIES AND MALE INFERTILY: A FRENCH COHORT STUDY Armin Priam, Amiens, France, Antoine Le Bozec, Kremlin Bicetre, France, Vasco Dias Meireles, Fabien Saint, Rosalie Cabry, Moncef Benkhalifa, Baptiste Demey, and Dorian Bosquet Armin PriamArmin Priam More articles by this author , Amiens Amiens More articles by this author , France France More articles by this author , Antoine Le BozecAntoine Le Bozec More articles by this author , Kremlin BicetreKremlin Bicetre More articles by this author , France France More articles by this author , Vasco Dias MeirelesVasco Dias Meireles More articles by this author , Fabien SaintFabien Saint More articles by this author , Rosalie CabryRosalie Cabry More articles by this author , Moncef BenkhalifaMoncef Benkhalifa More articles by this author , Baptiste DemeyBaptiste Demey More articles by this author , and Dorian BosquetDorian Bosquet More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003258.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The impact of HPV on the male genital tract remains largely underestimated and underexplored, compared to the female side. Epidemiological data in men are scarce, and few studies have investigated the prevalence of HPV in the male population and spermogram abnormalities. The objective was to study the prevalence of Human papillomavirus seminal carriage in male genital tract and its association with the spermogram and spermocytogram abnormalities. METHODS: From May to October 2021, patients were recruited in the SPERM-VIR study and provided semen samples. A total of 461 patients evaluated for fertility disorders was included. Individual informed consent was obtained to use biological, demographic, health, and lifestyle data. The spermogram, spermocytogram and sperm migration assays were carried out by the local Department of Medicine and Reproductive Biology. Then, overages of semen were sent to the local Virology Department for Human Papillomavirus (HPV) screening. Semen characteristics (semen volume, sperm concentration, total sperm count, sperm motility, sperm morphology, spermatic denaturation, spermatic DNA fragmentation, sperm migration test results), demographic, health, and lifestyle data of patients carrying or not HPV in the sperm were compared using univariate and multivariate analyses with a logistic regression model. RESULTS: HPV was detected in 22.34% of sperm samples. Multivariate analysis showed that positive HPV status was significantly associated with at least one spermogram abnormality, according to WHO 2021 standards (oligozoospermia and/or asthenozoospermia and/or teratozoospermia) with an adjusted odds ratio of 4.10 [95% CI 2.32-7.25]. This statistical association was also found for the type of infertility (OR: 1.61 [95% CI 1.00-2.57]), the notion of varicocele (OR: 3.99 [95% CI 1.48-10.71]), Cryptorchidism/Testicular Ectopy/Monorchidism antecedent (OR: 3.54 [95% CI 1.07-11.66]). Either mono or pluri-HPV infection were significantly associated with at least 1 spermogram abnormality (OR: 3.93 [95% CI 2.08-7.41] and 4.11 [95% CI 1.58-10.68], respectively), independently of HPV oncogenic risk. The association between HPV spermatic infection and the risk of infertility was significant in multivariate analysis (OR: 5.63 [95% CI 3.16-10.01]) and by adjusting to propensity score (OR: 6.10 [95% CI 3.33-11.21]). CONCLUSIONS: Our study is an additional argument supporting the impact of seminal HPV carrying on male infertility, especially in cases labelled as idiopathic. The determination of spermatic HPV could therefore be a part of the exploration of an infertile man Source of Funding: No external funding was received for this project. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e399 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Armin Priam More articles by this author Amiens More articles by this author France More articles by this author Antoine Le Bozec More articles by this author Kremlin Bicetre More articles by this author France More articles by this author Vasco Dias Meireles More articles by this author Fabien Saint More articles by this author Rosalie Cabry More articles by this author Moncef Benkhalifa More articles by this author Baptiste Demey More articles by this author Dorian Bosquet More articles by this author Expand All Advertisement PDF downloadLoading ...

HPV status and HPV16 viral load in anal cancer and its association with clinical outcome.

The incidence of anal cancer is increasing globally. Evidence-based improvement in early detection and management of this morbid cancer is thus required. In other cancers associated with Human Papillomavirus (HPV), viral status and dynamics, including viral load (VL) has been shown to influence clinical outcome. Our aim was to determine the influence of HPV status and HPV16 VL on the clinical outcomes of anal cancer patients. A total of 185 anal cancer lesions were genotyped for HPV. Of the HPV16 positive component, VL was determined using a digital droplet PCR assay. The association of qualitative HPV status and VL (low (<12.3), medium (12.3-57) and high (>57 copies/cell)) on overall survival and hazard of death was assessed. Of the 185 cases, 164 (88.6%) samples were HPV positive. HPV16 was detected in 154/185 samples (83.2%). HPV positive status was associated with improved overall survival in the univariate analysis [hazard ratio (HR) of 0.44, 0.23-0.82, p=0.01]. When adjusted by age, sex, stage and response to treatment, the association of positive HPV status with improved survival remained (HR 0.24 [0.11-0.55] p < 0.001). High VL was associated with improved overall survival in the univariate analysis with a HR of 0.28 (0.11-0.71, p=0.007). When adjusted only by age and sex, high VL was associated with better overall survival (HR 0.27, 0.11-0.68 p=0.006). HPV status appears to be independently associated with improved outcomes in anal cancer patients. Moreover, HPV viral load quantification may be informative for further risk stratification and warrants further investigation.

Tissue-resident memory T cells correlate with the inflammatory tumor microenvironment and improved prognosis in head and neck squamous cell carcinoma

ObjectivesTumor-infiltrating T cell (TIL) is a major cell type involved in tumor eradication in the tumor microenvironment (TME). Among TILs, tissue-resident memory T cells (TRMs) have been recognized as a subset capable of continuous immunosurveillance to afford long-term immunity. In the present study, we comprehensively profiled TRM in patients with head and neck squamous cell carcinoma (HNSCC). Materials and MethodsWe analyzed RNA-sequencing (RNA-seq) data obtained from The Cancer Genome Atlas (TCGA) database. Based on the gene expression of CD69 and CD4/CD8A, we identified TRM-enriched patients and evaluated their clinical and biological significance. In addition, we analyzed peripheral blood mononuclear cells (PBMCs) obtained from 60 patients with HNSCC to evaluate the presence of TRM-like cells in the peripheral circulation. ResultsTCGA analysis revealed that TRM-enriched tumors correlated with early T factor, human papillomavirus-positive status, the proportion of oropharynx lesion, upregulated inflammatory pathways, upregulation of immunostimulatory and immune checkpoint molecule genes, and favorable overall survival. Moreover, we clarified the presence of CD69 + TRM-like cells that highly express PD-1 and TIM-3 in the peripheral circulation of patients with HNSCC. ConclusionWe highlighted the clinical and transcriptomic significance of TRM in patients with HNSCC. Further characterization of TRM could lead to the development of novel biomarkers, especially for immune checkpoint therapies.

Mid-treatment Fluorodeoxyglucose Positron Emission Tomography in Human Papillomavirus-related Oropharyngeal Squamous Cell Carcinoma Treated with Primary Radiotherapy: Nodal Metabolic Response Rate can Predict Treatment Outcomes

AimsTo evaluate whether biomarkers derived from fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) performed prior to (prePET) and during the third week (interim PET; iPET) of radiotherapy can predict treatment outcomes in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPC). Materials and methodsThis retrospective analysis included 46 patients with newly diagnosed OPC treated with definitive (chemo)radiation and all patients had confirmed positive HPV status (HPV+OPC) based on p16 immunohistochemistry. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary, index node (node with the highest TLG) and total lymph nodes and their median percentage (≥50%) reductions in iPET were analysed, and correlated with 5-year Kaplan–Meier and multivariable analyses (smoking, T4, N2b-3 and AJCC stage IV), including local failure-free survival, regional failure-free survival, locoregional failure-free survival (LRFFS), distant metastatic failure-free survival (DMFFS), disease-free survival (DFS) and overall survival. ResultsThere was no association of outcomes with prePET parameters observed on multivariate analysis. A complete metabolic response of primary tumour was seen in 13 patients; the negative predictive value for local failure was 100%. More than a 50% reduction in total nodal MTV provided the best predictor of outcomes, including LRFFS (88% versus 47.1%, P = 0.006, hazard ratio = 0.153) and DFS (78.2% versus 41.2%, P = 0.01, hazard ratio = 0.234). More than a 50% reduction in index node TLG was inversely related to DMFFS: a better nodal response was associated with a higher incidence of distant metastatic failure (66.7% versus 100%, P = 0.009, hazard ratio = 3.0). ConclusionThe reduction (≥50%) of volumetric nodal metabolic burden can potentially identify a subgroup of HPV+OPC patients at low risk of locoregional failure but inversely at higher risk of distant metastatic failure and may have a role in individualised adaptive radiotherapy and systemic therapy.

Improvement of patient stratification in human papilloma virus-associated oropharyngeal squamous cell carcinoma by defining a multivariable risk score.

Precise risk stratification models are necessary to determine patient selection for deintensifying treatment trials in human papilloma virus (HPV)-associated oropharyngeal squamous cell cancer (HPV+ OPSCC). We examined 526 cases with OPSCC treated at our department between 2002 and 2017. Every patient was classified after the 7th and 8th edition UICC staging manual. For HPV+ OPSCC, we calculated a simple risk score with four risk groups based on multivariable Cox regression analysis of clinical and lifestyle parameters (UICC 8th edition stage, tobacco/alcohol abuse, age, gender). Two hundred and thirty-nine patients with OPSCC (45.4%) showed a positive histological HPV status. In comparison to UICC 8th edition stages, our proposed risk model showed a tendency for better stratification between risk strata I/III, I/IV, and II/IV (each p < 0.002) and I/II, II/III, and III/IV (each p < 0.09). Age, gender, tobacco, and alcohol abuse should be added to the current UICC staging system in order to improve risk stratification in HPV+ OPSCC.

The role of HPV gene expression and selected cellular MiRNAs in lung cancer development

BackgroundThe high mortality rate of lung cancer can be justified that strong need to explore new aspect of tumor biology. Human papillomavirus (HPV) has been detected as risk factor for the development of lung cancer. The aim of this study was to determine the role of HPV and cellular/miRNAs genes expression in the epithelial-mesenchymal transition (EMT) and development of lung cancer. MethodsIn this case-control study, 109 lung cancer tissue and 52 controls were included. We analyzed the presence of HPV infection, its genotypes (in positive samples) and the expression of viral genes (E2, E6 and E7). Also, We examined the expression of celluar factors including (a) p53 and retinoblastoma (Rb) (as anti-carcinogenic genes), (b) EMT related genes, (c) selected miRNAs. ResultsOur results reported 51.4% and 23.1% of HPV genome in tumor tissues and control tissues samples, respectively. There was a significant association between the HPV positive status and lung cancer (OR = 3.26, 95% C.I = 1.47–7.02, P = 0.001). HPV type 16 was the most prevalent genotype in tissues. The expression of p53, RB, TIMP1, CCNG-1, E-cad and PTPN13 were decreased while MMP-2 and N-cad were increased in HPV-positive tumor/control tissues compared to HPV-negative tissues. Also, among miRNAs, let-7, miR-23, miR-34, miR-125, miR-146 were downregulated and miR-20, miR-424 were upregulated in HPV-positve tissues compared to HPV-negative tissues. ConclusionThis study demonstrated that HPV infection and interaction with cellular genes and miRNAs promote EMT which involved in the lung cancer development.

The association between HPV gene expression, inflammatory agents and cellular genes involved in EMT in lung cancer tissue

BackgroundLung cancer is a leading cause of cancer morbidity and mortality worldwide. Several studies have suggested that Human papillomavirus (HPV) infection is an important risk factor in the development of lung cancer. In this study, we aim to address the role of HPV in the development of lung cancer mechanistically by examining the induction of inflammation and epithelial-mesenchymal transition (EMT) by this virus.MethodsIn this case-control study, tissue samples were collected from 102 cases with lung cancer and 48 controls. We examined the presence of HPV DNA and also the viral genotype in positive samples. We also examined the expression of viral genes (E2, E6 and E7), anti-carcinogenic genes (p53, retinoblastoma (RB)), and inflammatory cytokines in HPV positive cases.ResultsHPV DNA was detected in 52.9% (54/102) of the case samples and in 25% (12/48) of controls. A significant association was observed between a HPV positive status and lung cancer (OR = 3.37, 95% C.I = 1.58–7.22, P = 0.001). The most prevalent virus genotype in the patients was type 16 (38.8%). The expression of p53 and RB were decreased while and inflammatory cytokines were increased in HPV-positive lung cancer and HPV-positive control tissues compared to HPV-negative lung cancer and HPV-negative control tissues. Also, the expression level of E-cad and PTPN-13 genes were decreased in HPV- positive samples while the expression level of SLUG, TWIST and N-cad was increased in HPV-positive samples compared to negative samples.ConclusionOur study suggests that HPV infection drives the induction of inflammation and EMT which may promote in the development of lung cancer.

Association Between Positive Human Papillomavirus Status After Conization and Disease Recurrence in Patients with Cervical Intraepithelial Neoplasia Grade 3.

This study aimed to examine the associations of cone margin and human papillomavirus (HPV) status after conization with cytological abnormalities and disease recurrence in patients with cervical intraepithelial neoplasia grade 3 (CIN3). This is a retrospective study of 366 women with CIN3 who underwent conization at Kagoshima University Hospital between 2004 and 2017. Conization was performed using an ultrasonic scalpel. The polymerase chain reaction for detecting HPV genotypes was performed using fresh cervical cell samples. We examined the associations of margin status and HPV status after conization with cytological abnormalities and recurrence. Among 224 women with CIN3, 193 (86.2%) underwent HPV genotype testing before conization. The HPV-positive rate was 84.9%. The most common HPV genotypes before conization were HPV 16, 31, 58, 52, 18, 35, and 33. In 191 patients, the uterus was preserved after conization. Sixteen patients had pathologically positive margins, 165 had negative margins, and 10 had unclear margins. There was no significant difference in abnormal cytology and recurrence rate after conization between the three groups. Five patients with positive margins and abnormal cytology during follow-ups were HPV16- or HPV58-positive in the preoperative HPV testing. Of the 191 women, 91 (47.6%) underwent pre- and postoperative HPV genotype testing, among whom 14 (15.4%) were HPV-positive after conization. No significant difference in abnormal cytology based on HPV status after conization was found. The recurrence rate tended to be higher in HPV-positive patients than in HPV-negative patients after conization (21.4% vs. 1.3%, p < 0.05). Three patients with HPV positivity after conization and recurrence during follow-up were HPV16- or HPV58-positive. HPV positivity after conization for CIN3 was associated with a high recurrence rate, especially in HPV16- and HPV58-positive patients. HPV58 has not received much attention thus far, but abnormalities in cytology and recurrence may be as likely as those associated with HPV16. Thus, a careful follow-up in such patients is recommended.

Detection and Oncologic Outcomes of Head and Neck Squamous Cell Carcinoma of Unknown Primary Origin.

To assess factors that predict detection of tumors and oncologic outcomes in head and neck squamous cell carcinoma of unknown primary (SCCUP). This was a retrospective cohort study at a single tertiary care institution. The primary site was detected at examination under anesthesia (EUA) in 92 (51.1%) patients. The primary site was detected by directed biopsies in 60 (65%), palatine tonsillectomy in 28 (30.4%), and lingual tonsillectomy in 4 patients (4.3%). Four of eight lingual tonsillectomies were positive (50%). Primary locations included: palatine tonsils (51, 28.3%), base of tongue (37, 20.6%), larynx (4, 2.2%), oral cavity (3, 1.67%) and nasopharynx (1, 0.6%). Human papillomavirus (HPV) positive status (HR=0.26, p=0.004) and treatment with chemoradiation (CRT) (HR=0.38, p=0.004) were associated with better disease free survival (DFS). A primary site was located after aggressive investigation in approximately half of the patients. More research is warranted towards the use of lingual tonsillectomy. Predictors of favorable prognosis included HPV positive status and treatment with CRT.

Women's experiences of the renewed National Cervical Screening Program in Australia 12 months following implementation: a qualitative study.

ObjectiveTo explore women’s experiences of the renewed National Cervical Screening Program in Australia from the perspective of women who have received different human papillomavirus (HPV) test results. Women aged 25 to 74 are now screened every 5 years with primary HPV screening.DesignQualitative interview study.SettingAustralia.ParticipantsWomen in Australia aged 25 to 74 who reported participating in cervical screening since December 2017, purposively sampled by test result (HPV positive, HPV negative and HPV status unknown).Methods26 interviews with women aged 25 to 74 were conducted and analysed thematically.ResultsThree main themes emerged: knowledge and attitudes about the programme changes, information dissemination, the meaning and responses to test results and the new cervical screening test (CST). Some women showed little awareness of the changes, but others understood that HPV is detected earlier than abnormal cells. Some expressed positive attitudes towards the CST and were not anxious about less frequent screening. Most women envisaged the changes would have minimal impact on their screening behaviour. Women mainly wanted more information about the changes and the possible results from the new CST. Overall women could recall their HPV results and understand the implications for future cervical screening. Anxiety about being at ‘increased risk’ was more apparent in women who were HPV positive without history of abnormal results.ConclusionsWomen show some understanding of HPV and the new CST, but more written and public communication about the changes and possible results are warranted. Efforts are needed to ensure that women who are HPV positive without history of abnormal results receive the information needed to alleviate anxiety.

Prevalence and genotype distribution of human papillomavirus in women living with HIV/AIDS in an area of Northeast Brazil.

Women infected by human immunodeficiency virus (HIV) are more likely to manifest oncogenic viral infections including human papillomavirus (HPV). It was investigated the HPV prevalence, genotype distribution and HPV relationship with cervical lesions among women living with HIV in Sergipe state, Northeast Brazil. A prevalence survey was conducted including 270 HIV-infected women who attended the reference center for HIV in Sergipe from August 2014 to November 2017. Cervical samples were processed by the polymerase chain reaction for HPV-DNA detection. Among the 270 HIV-infected women, 190 (70.4%) were between 26 and 49 years old and 159 (55.6%) were coinfected with HPV. Among the coinfected women, 24 viral types were identified; 113 (72%) subjects had high-risk HPV types, and the most prevalent was HPV 16 (53/35.3%). Positive HPV status was statistically associated with having 0 to 8 years of schooling compared with≥9 years of schooling; and have been diagnosed with HIV infection less than 5 years ago compared with more than 10 years. Cytological abnormalities were found in 13.4% (31/231) of women, most with high-grade squamous intraepithelial lesions (16/51.6%). However, of women who had no cytological lesions or malignancy (200/86.6%), almost half were HPV DNA-positive (99/49.5%). In conclusion, the prevalence of HPV among women living with HIV in Sergipe was high. There was a high frequency of high-risk HPV infection, and a wide diversity of genotypes were detected, with HPV 16 being the most frequent.

Human papillomavirus and urinary bladder cancer revisited.

This review aims to present data on the association between human papillomavirus (HPV) and urinary bladder cancer (BC), especially of the subtype squamous cell carcinoma (SCC). Furthermore, the current data on the relation between p16, HPV, and BC are reviewed. PubMed was searched for 'Humans' [MESH] AND 'Papillomaviridae' [MESH] AND 'Urinary Bladder Neoplasms' [MESH], resulting in 157 potential articles. After profound reviewing, 18 articles were included in this review. Only original articles in English were included. A variable number of HPV genotypes in a small number of cases have been investigated in several studies with various methodology. HPV was present in 0-100% of cases depending on inclusion and exclusion criteria. SCC studies are mostly hampered by low number of cases whereas the few studies with a high number show a slightly higher prevalence of different HPV genotypes compared to pure urothelial carcinoma. Studies on p16 status in HPV positive cases are even more scarcely reported and show conflicting results. Most studies fail to prove clear-cut relevance of HPV in BC irrespectively of histological subtype. Negative p16 staining cannot rule out positive HPV status.

Poorly differentiated neuroendocrine carcinoma of the head and neck: human papillomavirus tumour status/p16 status and impact on overall survival

Poorly differentiated neuroendocrine carcinoma (PDNEC) of the head and neck is a rare high-grade neuroendocrine neoplasm. Human papillomavirus (HPV) status and p16 status are as yet unclear among PDNECs, owing to a lack of statistical analysis. The objective of the present study was therefore to evaluate their potential clinicopathological associations, and their prognostic impact on overall survival in PDNECs of the head and neck, regardless to HPV genotype. All cases of PDNEC of the head and neck between 1998 and 2019 were identified from the database of the Lyon university hospital pathology department (n=21); for these cases, p16 immunohistochemistry and HPV in-situ hybridisation were performed. Published cases of PDNEC of the head and neck with assessment of HPV status and p16 status were identified in PubMed (n=57). Local and published cases were pooled for analysis. HPV positive (HPV+) tumour status was found to be significantly associated with oropharyngeal localisation (P<0.001) and overexpression of p16 (P<0.001). Multivariate analysis, adjusted on tumour site, histological subtype, p16 status, HPV status, and source of the case, showed that oropharyngeal localisation [hazard ratio (HR) 3.031, 95% confidence interval (CI) 1.257-7.310] and being a small-cell variant (HR 2.859, 95% CI 1.150-7.109) were significant predictors of worse overall survival; HPV+ tumour status was associated with better overall survival (HR 0.388, 95% CI 0.146-0.995). HPV+ tumour status was associated with oropharyngeal PDNECs and with a better prognosis.