Human Papillomavirus Positive Patients Research Articles

B-353 High risk HPV genotypes prevalence in Mexico

Abstract Background The greatest risk factor for the development of cervical cancer is infection by human papillomavirus (HPV). To date, more than 200 genotypes have been described, 14 of them considered by the WHO as high risk genotypes (HR) due to their high oncogenic capacity, with special attention given to genotypes 16 and 18. In Mexico, cervical cancer is the third cause of cancer-associated death in women, therefore, the timely detection of HR genotypes in women becomes imperative for the reduction of the burden of this disease. The detection of high-risk HPV genotypes through the PCR molecular test is part of primary cervical cancer screening, however, this practice is not common in Mexico. Here, we analyzed the results of HPV genotyping studies in women attending cervical cancer screening studies at Salud Digna with the objective of determining the prevalence and dsitribution of HR-HPV in Mexico. Methods Retrospective analysis of the results obtained for the detection of HPV in cervical samples from patients who were attended at Salud Digna clinics from june to august 2023. The samples were processed by automated RT-PCR (ROCHE COBAS PRIME-Cobas 6800). The kit used was the COBASHPV which detects the 14 HR genotypes and generates 4 types of results: negative, positive for HPV16, positive for HPV18 and positive for POOL (which includes the remaining 12 genotypes). For the analysis, Mexico was divided into 7 regions which share sociocultural factors (Northwest, North, West, Center, Gulf, South, Southeast). Results The study population was 95,934 patients (mean age of 41y). At the national level, 18.93% (18,159) of patients are positive for HPV POOL, 3.54% (3,399) for HPV 16 and 1.78% (1709) for HPV 18. The regions with the highest positivity are the southeast region for HPV POOL (22.32%), the south region for HPV 16 (3.77%) and HPV 18 (2.44%) while the region with the lowest percentage is the Northwest region (HPV POOL 17.86%, HPV16 3.39%, HPV18 1.57%). The age range with the highest percentage of positivity is 14-29y for HPV POOL, 30-39y for HPV 16, and 30-39y for HPV 18. Conclusions We found that Mexican patients are becoming infected at an early age with the genotypes that are part of the pool, however, we observe a marked trend towards a decrease in cases as the age of the population advances.The regions of the country with a higher percentage of HPV positive patients are the south and the southeast, regions that also concentrate most of the extreme poverty in Mexico. These numbers should be taken with caution given that in absolute values these are also are the regions of the country where the least people go for a cervical cancer screening study, emphasizing the need to promote these studies in these regions. In the case of genotypes with a greater oncogenic capacity, both HPV16 and HPV18 show a greater prevalence in economically productive age ranges. Retrospective studies like provide information that allow governments to generate public policies focused on the most affected regions.

Triage performance of PAX1m/JAM3m in opportunistic cervical cancer screening of non‒16/18 human papillomavirus-positive women: a multicenter prospective study in China

ObjectivesIn this study, we aimed to validate the performance of the PAX1 and JAM3 methylation (PAX1m/JAM3m) test as a triage tool for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in non-16/18 high-risk human papillomavirus-positive patients (non-16/18 hrHPV +).MethodsThe triage performance of liquid-based cytology (LBC) and the PAX1m/JAM3m test for detecting CIN3 + were compared.ResultsIn total, 1851 participants had cervical histological outcomes and were included in the analysis. The sensitivity/specificity of the LBC test results with atypical squamous cells of undetermined significance or worse (LBC ≥ ASCUS) and the PAX1m/JAM3m test were 90.1%/26.7% and 84.8%/88.5%, respectively. PAX1m/JAM3m( +) had the highest diagnostic AUC (0.866, 95% confidence interval (CI) 0.837–0.896) in the whole cohort. All cancers (n = 20) were detected by PAX1m/JAM3m(+). Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of patients who needed referral for colposcopy by 57.21% (74.66% vs. 17.45%). The odds ratios for detecting CIN3 + by LBC ≥ ASCUS and PAX1m/JAM3m(+) were 3.3 (95% CI 2.0–5.9) and 42.6 (27.1–69.6), respectively (p < 0.001). The combination of LBC ≥ ASCUS or PAX1m/JAM3m(+) slightly increased the diagnostic sensitivity (98.0%, 95% CI: 95.8–100%) and referral rate (77.09%) but reduced the diagnostic specificity (24.8%, 22.7–26.8%).ConclusionsIn non-16/18 hrHPV(+) women, PAX1m/JAM3m was superior to cytology for detecting CIN3 + . Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of significant referrals to colposcopy without compromising diagnostic sensitivity.

High-risk human papilloma virus status & outcomes for penile squamous cell carcinoma: A single institution experience

ObjectivesThere 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. MethodsPatients 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. ResultsThe 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). ConclusionsWe 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.

Differential gene expression and methylation of upper aerodigestive tract and lung squamous cell carcinoma between European ancestry (EA) and African ancestry (AA) patients.

e18031 Background: Pan-cancer analysis of cancer disparities revealed both head and neck and lung cancer are among the top cancers with significant disparities in overall survival outcomes between EA and AA patients. Analysis of The Cancer Genome Atlas (TCGA) for all cancer in EA and AA found genetic signatures associated with noted disparities, such as somatic copy number alterations, TP53 mutations, CCNE1 amplification, and overexpression of genes correlated with chromosomal instability. To inform whether epigenetic and transcriptomic factors could be driving the disparities seen in squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT) and lung, we sought to analyze genomic data to identify differentially methylated and expressed genes between EA and AA patients and determine whether these affected survival. Methods: TCGA was queried to extract data from self-identified EA and AA patients with head and neck, esophageal, and lung SCC. Literature suggests that SCC tumors share genetic and epigenetic signatures and can be analyzed as a group. Human papillomavirus positive patients were excluded. Patients were separated into EA and AA groups matched for age, stage, and smoking to account for clinical biases of biological analysis. DNA methylation (Epic array) and gene expression (RNA-Seq) profiles were compared between tumor tissue samples in EA patients, tumors in AA patients, and normal tissue. The genes that were identified to be differentially methylated were then analyzed to compare overall survival between hypomethylation and hypermethylation of each identified gene, with and without subgrouping by race. Differentially expressed genes were similarly analyzed between high and low expression. Overall survival was estimated by the Kaplan-Meier method and compared using the log-rank test. Results: A comparison of DNA methylation profiles found 79 genes that were differentially methylated when comparing EA tumor, AA tumor, and normal tissue samples. Survival analysis was performed on top 21 of the differentially methylated genes. Of these, 9 were found to have significant differences in overall survival when stratifying by race and methylation status. Differentially methylated genes included MAD1L1 (Mitotic Arrest Deficient 1 Like 1), which is known for its role in the spindle assembly checkpoint in mitosis and tumor suppression. Similar analysis revealed 404 genes that were differentially expressed comparing EA tumor, AA tumor, and normal tissue. Candidate genes based on expression level will be discussed. Conclusions: Differential DNA methylation and gene expression were noted between EA and AA groups with lung and UADT SCC. This difference may contribute to the disparity in overall survival seen between these groups that persists even when controlling for variables commonly associated with worse survival.

Treatment Delay and HPV Status on OPSCC With Upfront Surgery: Analysis of National Cancer Database.

Evaluate the effect of treatment delay on survival in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC) patients undergoing primary surgical resection. Retrospective cohort study using the 2010-2017 National Cancer Database. Multicenter database study. Patients >18 years old with OPSCC and known HPV status, treated surgically with or without postoperative radiation/chemotherapy were included. Two cohorts based on HPV status were grouped by time to treatment initiation (TD-TI, ≤30, 31-60, ≥61 days) and surgery to radiotherapy (TS-RT, ≤42, 43-66, ≥67 days). Univariate, Kaplan-Meier, and multivariate analyses assessed correlations between demographic and clinical factors with overall survival in treatment delay groups. Included were 1643 HPV-positive OPSCC patients and 391 HPV-negative OPSCC patients. No associations between survival and gender, age, race, insurance, or radiotherapy length were observed. Regardless of HPV status, larger tumor size (>2 cm) and lymphovascular invasion predicted worse survival. HPV negative patients with >4 lymph nodes involved had 2.5×greater mortality risk (P = .039). Robotic surgery was associated with improved survival only in HPV positive patients (hazard ratio [HR]: 0.41, P < .001). In HPV positive patients, higher TD-TI related to lower mean survival, although this was not significant on multivariate analysis. HPV negative patients with >42 days of TS-RT had decreased survival (43-66 days, HR 1.63, P = .049; ≥67 days, HR 2.10, P = .032). Longer TS-RT was associated with lower overall survival in HPV negative patients. Treatment delay was not associated with survival in HPV positive OPSCC according to multivariate analysis. These findings enhance knowledge about treatment delay effects in OPSCC, aiding providers in decisions and patient communication.

The role of endocervical curettage in the diagnosis of cervical intraepithelial neoplasia in human papillomavirus positive patients.

The role of endocervical curettage (ECC) in the diagnosis of cervical intraepithelial neoplasia (CIN) is a controversial topic. Investigate the role of ECC in the diagnosis of CIN in human papillomavirus (HPV) positive patients. Retrospective. A tertiary training and research hospital. This study included patients who were referred for colposcopy between 2018-2022 because of abnormal screening results. ECC results, age, cytology, HPV status, and colposcopic impression of the patients were extracted from the medical records. Multinomial logistic regression analyses were performed to identify factors that could predict CIN on ECC. The likelihood of high-grade squamous intraepithelial lesions (HSIL) in ECC in patients with cervical biopsy results of normal and low-grade squamous intraepithelial lesion (LSIL). 2895 women. In patients with normal and LSIL cervical biopsy results, HSILs were detected in 6.7% of ECC results. There was no difference in the detection rates of CIN in ECC among groups with smear results negative for intraepithelial lesions or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), and LSIL. The likelihood of HSIL being observed in ECC was 2.2 times higher in patients with HPV16. The probability of LSIL disanois was 2.3 times higher in women aged 50-59 years and 2.8 times higher in women ≥ 60 years compared to the reference group of <30 years. The probability of LSIL was 2.3 and HSIL by ECC was 2.2 times higher in both age categories (P<.012 and P=.032, respectively) than the reference group of <30 years. Regardless of colposcopic findings, ECC should be performed in patients with smear results of NILM who are positive for HPV16, in patients with smear results of ASC-US and LSIL who are positive for any oncogenic type of HPV and in patients 50 and above with any result of smear or any oncogenic HPV type. We did not have the components of the HPV types in mixed groups.

Current Status of Vaccine of Human Papillomavirus-positive Patients with Oropharyngeal Carcinoma

Abstract The oropharynx is amongst the most common sites of cancer in Indian male population. The human papillomavirus (HPV) infection causes approximately 5% of cancers worldwide. HPV-positive patients (12–16 HPV genotypes) with oropharyngeal carcinoma (OPC) of the tonsil and base of the tongue are increasing significantly not only in India but also in the USA and some European countries. The abovementioned facts were the driving force to conduct this present study. The aims of the present were (1) To know the relationship between the HPV vaccination and the incidence of OPC in men and (2) Can pan-gender HPV vaccination reduce the incidence of HPV patients with OPC. The study reviewed the literature using MEDLINE/PubMed and Google Scholar. The English language articles having abstracts were included on 28 March 2024. The study investigated the effect of HPV vaccination on the incidence and prevalence of HPV-positive men with OPC in the last 3 years (January 2021 to December 2023). The current study observed HPV vaccination reducing the oral HPV positivity in men and indicating the decreased risk of developing HPV-positive patients with not only OPC but also other HPV-associated head-and-neck cancers. The study found that the introduction of pan-gender HPV vaccination can reduce the incidences of HPV-positive men with OPC. Therefore, HPV vaccination in pre-teens, early teens and young boys can prevent not only HPV-positive men with OPC but also other cancers of head-and-neck regions.

Recurrence free survival in patients with HPV+ head and neck cancer treated with TORS and neck dissection.

e18076 Background: Prior research has demonstrated that delays to initiation of radiation therapy (RT) in the treatment of head and neck squamous cell carcinoma (HNSCC) after surgery result in poorer survival outcomes. However, there is limited data with little long-term follow up to evaluate whether human papilloma virus (HPV) positive primaries undergoing transoral robotic surgery (TORS) and neck dissection (ND) face a similar decrement in recurrence free survival (RFS) and disease specific survival (DSS). Methods: Single center retrospective chart review of patients diagnosed with HPV positive primary nonmetastatic HNSCC who underwent TORS with ND followed by RT with or without Chemotherapy and/or Immunotherapy from 2012-2022 with data collection from December 2022 to February 2023. 248 patients met inclusion criteria and were analyzed for DSS and RFS. Kaplan-Meier survival analysis with Log-rank testing was used to assess the impact of time intervals between diagnosis, TORS, radiation initiation and radiation completion on survival. Univariable and Multivariable Cox proportional hazards regression analysis was performed to identify factors associated with RFS and DSS and adjust for potential confounding variables. Subgroup analysis was completed with high risk (lymph nodes &gt; 4 with extracapsular extension) and low risk population. Results: Median follow-up time was 47.22 months (1452.07 days). Of 248 patients, 17 had a recurrence and 12 died due to disease. In patients who underwent radiation therapy for a time frame (TR1-R2) of 5-7 weeks compared with those who had a shortened or prolonged course of RT, RFS (140.116 months, p-value = .012) and DSS (142.641 months, p-value = .016) were improved. Although time from diagnosis to TORS did not impact RFS (p-value = .195), improved RFS persisted in patients who underwent time from diagnosis to radiation completion (TD-R2) or total treatment package time (TTPT) between 17-20 weeks (109.155 months, 95% CI: 105.276-113.034, p-value = .057) compared to patients with TTPT less than 17 or greater than 20 weeks. When the population is stratified into high risk and low risk groups, patients in the high risk group who underwent Chemotherapy had improved RFS compared to no chemotherapy (HR: 7.19, p-value = .09). On Univariate Analysis, TR1-R2 &lt; 5 weeks and &gt; 7 weeks, TD-R2 &lt; 17 weeks and &gt; 20 weeks, extracapsular extension, smoking history, and age &gt; 70 were associated with increased risk of recurrence. Conclusions: For HPV positive patients with OPSCC undergoing TORS and Neck dissection, time to radiation initiation may not be as critical in improving OS, DSS, and RFS as other patient populations. However, the length of radiation time between 5 to 7 weeks and overall treatment time from 17-20 weeks may improve recurrence free survival and disease specific survival.

An Integrative Approach, by Using A Bi-digital O-Ring Test (BDORT), Advanced Bioinformatics, and Clinical Testing for the Development of New Effective Treatment of Infections Caused by Human Papillomaviruses (HPV)

Introduction: HPV is a family of double-stranded DNA viruses that infect the mucous epithelium. Most of these infections regress without consequences; however, the high-risk HPV viral strains can determine a tumor transformation of the epithelium, giving rise to tumor forms such as cervical cancer. The analysis mostly applied to define abnormalities of the membranes is the PAP test and the treatment is reconciled, in most cases through prevention. Alongside the standard protocol, we have determined that a blend of essential oils has an effect in determining the negativization of HPV. Materials and Methods: We made use of the BDORT technique in order to determine the specific percentages of each component of the prepared oil blend. To confirm this, two advanced Molecular Docking software have been applied (Swiss Dock and 1-Click Docking). The mixture of oils was subsequently applied, in the form of vaginal capsules, on a group of HPV (+) positive patients, who were tested for the presence of a virus, before and after treatment, by RT-PCR, Colposcopy, and BDORT to evaluate the state of epithelium before and after the assumption of oil vaginal capsules. Results: The mixture of oils has produced the negativization of HPV, determined by BDORT and confirmed by RT-PCR, in the treated patients. Discussion: We have determined that the blend of essential oils, prepared here, influenced the negativization of the virus, in all the patients treated. Conclusions: The operative efficacy of these oils in the negativization of HPV has been demonstrated.

Distribution of human papilloma virus genotypes and treatment outcomes in definitive radiotherapy for cervical cancer.

Most oncogenic human papilloma virus (HPV) genotypes stratify into two species, α-7 HPV and α-9 HPV. There are several studies that evaluate the relationship between HPV species and treatment outcomes and reports that HPV species is prognostic. The HPV genotyping was conducted using biopsy specimens which had been stored in these studies. We conducted the study using the HPV test performed by cytology specimens which is less invasive and more useful in clinical settings. This study enrolled 46 patients who received HPV genotyping before the definitive radiotherapy. The results of the HPV genotyping were classified into HPVα-7, HPVα-9 and negatives. Of the 46 patients, 10 were positive for HPVα-7, 21 positive for HPVα-9 and 15 were negative. The median follow-up period was 38months (range 4-142). The HPVα-7, HPVα-9 and negative groups showed the 3-year overall survival (OS; 59.3%, 80.4% and 72.2% [P = 0.25]); local control (LC; 67.5%, 81% and 80% [P = 0.78]); pelvic control (PC) (50%, 81% and 72.7% [P = 0.032]); pelvic lymph node (PLN) control (78.7%, 95% and 92.3% [P = 0.012]); distant metastasis free (DMF) survival (50%, 75.4% and 42.8% [P = 0.098]); and progression free survival (PFS) rate of patients (30%, 66.7% and 38.9% [P = 0.085]), respectively. Patients with HPVα-7 showed statistically significant poorer PC than the HPVα-9 group, in multivariate analysis. This result is consistent with previous studies for HPV positive patients. The HPV negativity rate was higher in this study than in other studies and further work on this may be needed for clinical use.

Association between Human Papillomavirus and Oral Cancer in Iranian Clinical Samples: A Meta-Analysis Review.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies and is a serious problem worldwide. The role of HPV in oral cavity squamous cell carcinoma has been studied in several researches. This present review and meta-analysis aimed to investigate the relation between human papillomavirus (HPV) and oral cancer. Relevant studies were found using online international databases including Science direct, Web of science (ISI), PubMed, Scopus, Embase, and Google scholar, to determine relevant studies published between 2000 and Jan 2020. Suitable studies were selected and assessed by two independent researchers. The quality of all papers were determined by a checklist. Heterogeneity assay among the primary studies was evaluated by Cochran's Q test and I2 index. The statistical analyses were done using Stata SE, V.11 software. Trim and Fill method was applied to confirm the validity of the results. This meta-analysis consists of 8 primary studies on the incidence of HPV infection in Iranian patients with oral diseases. The odds ratio between HPV infection and risk of oral cancer was 4.00 (95%CI: 2.31, 6.93). This meta-analysis showed associations between prevalence of HPV infection and oral cancer among Iranian patients. The chance of developing oral cancer among HPV positive patients was higher than that in HPV negative patients.

Human papillomavirus, tobacco, and poor oral hygiene can act synergetically, modulate the expression of the nuclear factor kappa B signaling pathway for the development and progression of head and neck cancer in the Pakistani population.

Background:Head and neck cancers (HNCs) are a heterogeneous group of tumors that progress owing to varied enviromental and genetic risk factors. Viral infections are threatening and adept at altering the expression of cellular transcription factors such as nuclear factor kappa B (NF-κB) and deregulation of other cellular proteins like NF kappa B inhibitor alpha (IκBα). The present study was conducted to detect high-risk genotypes of human papillomavirus (HPV) and protein expression of NF-κB signaling pathway in HNC patients with HPV infection.Methods:For HPV detection, genomic DNA from 152 HNC tumors was extracted formalin-fixed paraffin-embedded tissue DNA kit. For genotyping, polymerase chain reaction (PCR) using a general primer, HPV type-specific primers and agarose gel electrophoresis were performed. Immunohistochemistry (IHC) was also performed on 4-μm thick tissue sections using HPV E6 monoclonal antibody. Protein expression analysis of NF-κB signaling pathway including p50, p65, and IκBα was performed using IHC.Results:PCR analysis showed that 24.3% (37/152) of HNC cases were HPV positive. Among HPV positive, 86.5% (32/37) were tobacco users, while among HPV negative, 66.9% (77/115) were tobacco users. A significant association of HPV positivity and tobacco user was observed by univariate analysis [P < 0.01; odds ratio (OR): 0.310, 95% confidence interval (CI): 0.110 to 0.870]. More HPV positive patients were with poor oral hygiene (78.3%) when compared with patients with good oral hygiene (21.6%) [P < 0.03, OR: 2.440, 95% CI: 1.650 to 3.600]. The results of the logistic regression analysis showed that age, tobacco use and oral hygiene are significant predictors (P < 0.02). PCR and IHC staining results confirmed that HPV16 was predominant among HNC cases (64.8%) when compared with HPV18 (35.2%). Expression of NF-κB proteins (p50, p65, and IκBα inhibitor) were also observed in HPV and non-HPV infected HNC tissues. IHC expression of p50, and p65 showed nuclear staining, while IκBα inhibitor showed cytoplasmic staining. Protein expression in HPV cases was higher as compared to HPV naive cases (P < 0.05).Conclusions:From the study, it can be established that the use of tobacco, oral hygiene, and HPV infection may be synergistically involved in modulating the expression of NF-κB signaling pathway for the development and progression of HNC in the Pakistani population.

Overexpression of miR-3653 is Associated with HPV Infection and Serves as a Biomarker in Patients with Cervical Cancer.

BackgroundHuman papillomavirus (HPV) is a major cause of cervical cancer (CC) occurrence. This study aimed to explore whether abnormal microRNA (miR)-3653 is associated with HPV infection and to investigate the clinical value of miR-3653 in the diagnosis and prognosis of CC.MethodsTumor tissues and adjacent non-cancerous tissues were collected from 136 patients with CC. Cervical tissues from 101 patients with uterine fibroids were collected as controls. The expression of miR-3653 was measured by quantitative real-time PCR. The ability of miR-3653 to discriminate between HPV positive (HPV+) and HPV negative (HPV-) CC patients, and to discriminate patients from controls was assessed by receiver operating characteristic analysis. Kaplan–Meier curves and Log rank tests were used to evaluate the relationship of miR-3653 with survival of CC patient. Whether miR-3653 could function as a prognostic indicator was evaluated by univariate and multivariate Cox analyses.ResultsmiR-3653, highly expressed in CC tissues, was associated with HPV infection, tumor diameter, International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis in CC patients. Additionally, miR-3653 was increased in HPV+ controls, CC patients and CC cells. Moreover, miR-3653 could screen HPV+ controls, screen HPV+ patients and screen CC patients. Furthermore, miR-3653 was associated with the survival of CC patients (log-rank P < 0.001) and could serve as an independent prognostic indicator for CC patients.ConclusionmiR-3653, increased in CC, is related to HPV infection and may serve as a diagnostic and prognostic biomarker for CC patients.

Human papilloma virus integration sites and genomic signatures in head and neck squamous cell carcinoma.

A prevalence of around 26% of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has been previously reported. HPV induced oncogenesis mainly involving E6 and E7 viral oncoproteins. In some cases, HPV viral DNA has been detected to integrate with the host genome and possibly contributes to carcinogenesis by affecting the gene expression. We retrospectively assessed HPV integration sites and signatures in 80 HPV positive patients with HNSCC, by using a double capture‐HPV method followed by next‐generation Sequencing. We detected HPV16 in 90% of the analyzed cohort and confirmed five previously described mechanistic signatures of HPV integration [episomal (EPI), integrated in a truncated form revealing two HPV‐chromosomal junctions colinear (2J‐COL) or nonlinear (2J‐NL), multiple hybrid junctions clustering in a single chromosomal region (MJ‐CL) or scattered over different chromosomal regions (MJ‐SC) of the human genome]. Our results suggested that HPV remained episomal in 38.8% of the cases or was integrated/mixed in the remaining 61.2% of patients with HNSCC. We showed a lack of association of HPV genomic signatures to tumour and patient characteristics, as well as patient survival. Similar to other HPV associated cancers, low HPV copy number was associated with worse prognosis. We identified 267 HPV‐human junctions scattered on most chromosomes. Remarkably, we observed four recurrent integration regions: PDL1/PDL2/PLGRKT (8.2%), MYC/PVT1 (6.1%), MACROD2 (4.1%) and KLF5/KLF12 regions (4.1%). We detected the overexpression of PDL1 and MYC upon integration by gene expression analysis. In conclusion, we identified recurrent targeting of several cancer genes such as PDL1 and MYC upon HPV integration, suggesting a role of altered gene expression by HPV integration during HNSCC carcinogenesis.

Prevalence of human papilloma virus (HPV) genotypes between outpatients males and females referred to seven laboratories in Tehran, Iran

BackgroundHuman papilloma virus (HPV) causes the most common sexually-transmitted infection especially among sexually-active individuals. The aim of study was to characterize the molecular characterization of HPV genotypes between 5176 female and male patients.MethodsHPV DNA was extracted from genital swabs of the study participants and amplified by Real Time Polymerase Chain Reaction (PCR). Genotyping was performed for 2525 cases using REALQUALITY RQ-Multi HPV Detection Kit for the identification of 14 high risk (HR) and 2 low risk (LR) HPV genotypes. Demographic figures were analyzed in correlation with virological data statistically.ResultsOut of 5176 cases from 7 laboratories, 2727 (53%) were positive for HPV, of which. 2372(87%) women and 355 (13%) men were HPV positive. However, in an intra-gender analysis, positive rate was higher in men (355/637, 55.7%) than in women (2372/4539, 52%; P value 0.007). HPV positive patients were younger than negative individuals. Positive rate was higher among age categories 20–40. Genotyping was performed for 2525 cases. Out of 1219 (48%) patients who contained single genotypes, 566 (22%) and 653 (26%) harboured HR and LR genotypes, respectively. In females and males, 1189 (54%) and 117 (37%) contained multiple genotypes. No substantial associations were found between different age categories and HR/LR and multiple genotypes distribution.ConclusionThe prevalence of HPV infection in both genders was high. However, men had a higher rate of infection. These observations highlighted the necessity for a plan for targeted education to younger population in the society as well as application of infection control measures against HPV infection, especially in terms of general population mass HPV vaccination.

Epidemiological Aspects of Age and Genotypical Occurrence of HPV Infection Among Females of Canton Sarajevo Over a 10-year Period.

Human papillomaviruses (HPV) are one of the most prevalent causes of cervical, anal, and oral cancer, and it is believed that nearly all sexually active males and females have been infected with HPV at some point in their lives. The purpose of this study is to highlight epidemiological characteristics of the age and genotypical incidence of HPV infection among females in Canton Sarajevo during a 10-year period. This cross-sectional study was conducted in the period between January 2012 and December 2021 at the medical institutions "Zavod za Ginekologiju, Perinatologiju i Neplodnost "Mehmedbašić" among females who were admitted for a routine gynaecological exam in Canton Sarajevo in Bosnia and Herzegovina. In total, 1517 patients who reported typical sexarche at 18.35±1.92, having one 721 (47.5%) sexual partner, regular use of contraceptive methods 820 (54.5%) with male condom 513 (62.6%) being the dominant choice of contraception and having gynacological hereditary oncological positive history 141 (9.3%), were included in the study from which 653 (43.05%) patients had positive HPV test and 864 (56.95%) had negative HPV results. HPV positive patients, 386 (59.1%) were infected either with one type of virus only, while 267 (40.9%) patients were infected with multiple virus strains where we have identified 166 virus strain combinations. Analysis showed that the patients infected by only one virus strain were one of next specific HPV viruses: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. HPV-16 was the predominately strain 16 (22.5%) identified among all the patients. Mean age of HPV positive patients was 33.38±7.85, ranging from 18 to 61 years. This study highlights the significance of the most frequent HPV high-risk strains (HPV-16, -18, -31.-33,-45,-52, and -58) among the Bosnia and Herzegovina population as one of the most common cancer-causing strains worldwide.

CD68+ Macrophage Infiltration Associates With Poor Outcome of HPV Negative Oral Squamous Carcinoma Patients Receiving Radiation: Poly(I:C) Enhances Radiosensitivity of CAL-27 Cells but Promotes Macrophage Recruitment Through HMGB1.

Patients with human papillomavirus (HPV) negative oral squamous cell carcinoma (OSCC) generally have poor clinical outcomes and worse responses to radiotherapy. It is urgent to explore the underlining mechanisms of the distinct prognoses between HPV negative and HPV positive OSCC and to develop effective therapy strategy to increase the survival rate of HPV negative OSCC patients. We conducted a retrospective cohort of 99 resected OSCC patients to evaluate the prognosis of HPV negative and HPV positive OSCC patients receiving radiation or not. We further addressed the association of CD68+ macrophage infiltration with HPV status and the effects on survival of OSCC patients. We also used the TCGA-OSCC cohort for further verification. Based on the cohort study, we applied a synthetic dsRNA polymer, polyriboinosinic-polyribocytidylic acid (poly(I:C)), on CAL-27 (HPV negative OSCC cells). We co-cultured its condition medium with THP-1 derived macrophage and examined the cytokines and macrophage migration. We found that high CD68+ macrophage infiltration associated with poor overall survival in HPV negative OSCC patients receiving radiation. In vitro, poly(I:C) could induce apoptosis and enhance the radiosensitivity, but increase macrophage recruitment. Targeting HMGB1 could inhibit IL-6 induction and macrophage recruitment. Our findings indicated that CD68+ macrophage might play an important role in the outcomes of HPV negative OSCC patients receiving radiation. Our findings also suggested that radiation combined poly(I:C) might be a potential therapy strategy to increase the radiation response and prognosis of HPV negative OSCC. Notably, HMGB1 should be targeted to inhibit macrophage recruitment and enhance overall therapy effects.

The Prevalence of High-risk Human Papillomavirus Type 16 and 18 in Women in Rasht-Iran

Background & aim: Cervical cancer is one of the leading causes of cancer death among females. Human papillomavirus (HPV) is the most important risk factor for cervical cancer. The aim of the present study was to explore the prevalence of high-risk human papillomavirus types 16 and 18 in women who undergo HPV test. Methods: In this descriptive epidemiological study, which was conducted in Mehr Medical Institute, Rasht, Iran from 2019 to 2020, two cervical samples were obtained from each of 301 patients for cytological and real-time PCR evaluation. Genotyping the samples was carried out using the Real-Time PCR technique. Different genotypes were divided into the following groups: 16 and 18 genotypes, other high risk genotypes, possibly low risk and high risk genotypes. Results: The prevalence of HPV types in the study participants with a mean age of 33.4± 6.5 (18-61) years were 36.5% (n=110). HPV16 and 18 were detected in 28 (25.7%) and 7 patients (6.4%), respectively. Histopathological findings among HPV positive and negative participants were similar. HPV distribution according to women´s age was: group 1 (20-24.9 years, 47%), group 2 (25-29.9 years, 42.6%), group 3 (30-34.9 years, 40.4%), group 4 (35-39.9 years, 27.6%) and group 5 (40≤ years, 28.3%). Conclusion: The general percentage of HPV positive patients in the local area can be compared to the previous literature. The study includes updates on the prevalence and type of HPV distribution between women of Guilan province in Iran.

Performance of a six-methylation-marker assay on self-collected cervical samples – A feasibility study

ObjectivesIn high-income countries, a high proportion of cervical cancers is diagnosed in screening non-attendees. One approach to improve screening coverage is to offer self-sampling for human papillomavirus (HPV) testing. However, especially young women are often HPV positive without having a precancerous lesion in need of treatment. To improve the rather low specificity of HPV testing additional markers such as DNA-methylation can be used. The aim of this feasibility study was to examine the performance of the methylation marker assay GynTect®, comprising six methylation markers, on dry self-collected cervico-vaginal samples compared to physician-taken samples. MethodsWe recruited 89 patients from our colposcopy clinic of whom 87 qualified for the study. The women took a self-sample with the Evalyn-Brush. Afterwards the planned colposcopy was performed and smears for cytology and reference HPV testing were taken as well as a biopsy in cases of abnormalities. Physician-taken and self-collected samples were tested for HPV DNA and were analyzed with GynTect®. ResultsWe obtained 95.5 % valid results for the self-collected samples which was very close to the physician-taken samples. Only about half of the self-collected samples were GynTect® positive in comparison to the physician-taken samples. GynTect® scores were significantly lower for self-collected than for physician-taken samples (p = 0.001, paired t-test). The overall concordance for GynTect® results was moderate (kappa 0.394; p < 0.001). For HPV testing we obtained a good concordance (kappa 0.586; p < 0.001). The GynTect® results for the self-collected samples showed a sensitivity for the detection of cervical intraepithelial neoplasia 2 or worse (CIN2+) of 26.1 % (95 %-CI: 0.13−0.46) and a specificity of 95.6 % (95 %-CI: 0.85−0.99), in comparison to a sensitivity of 45.5 % (95 %-CI: 0.27−0.65) and a specificity of 78.3 % (95 %-CI: 0.64−0.88) for the physician-taken samples. ConclusionsGynTect® methylation marker testing has a satisfactory amount of valid results on self-collected samples. However, the results of the self-collected samples differed clearly in comparison to the reference samples. To justify an application in screening, a larger study with more cases of high-grade cervical dysplasia and HPV positive patients will be needed.

Prognostic value of FGFR1 expression and amplification in patients with HNSCC: A systematic review and meta-analysis.

Fibroblast growth factor receptor 1 (FGFR1) has recently been identified as a promising novel therapeutic target and prognostic marker in different types of cancer. In the present study, a meta-analysis was performed to clarify the correlation between FGFR1 and the survival outcomes of head and neck squamous cell carcinoma (HNSCC) patients. PubMed, Embase, and Web of Science were systematically searched for relevant studies in order to explore the prognostic significance of FGFR1 in HNSCC. Hazards ratios (HR) and 95% confidence intervals (CI) were collected to estimate the correlation between overexpression and amplification of FGFR1 and survival outcomes of HNSCC patients. Nine studies including 2708 patients with HNSCC were finally selected for the meta-analysis. The results indicated that FGFR1 predicted poor overall survival (OS) (HR, 1.97; 95% CI, 1.49–2.61, P<0.001) in HNSCC patients. Futhermore, FGFR1 was related to poor OS in human papillomavirus (HPV) negative HNSCC not in HPV positive HNSCC patients. Subgroup analysis stratified by molecular abnormalities, such as overexpression or amplification showed the similar results. The present study demonstrated that HNSCC patients with FGFR1 overexpression and amplification were more likely to exhibit poorer survival.