High-risk High-risk Human Papillomavirus Types Research Articles

Comparative evaluation of Anyplex II HPV28 and Allplex HPV28 molecular assays for human papillomavirus detection and genotyping in anogenital cancer screening.

Persistent infection with high-risk human papillomavirus (HPV) is recognized as the main cause for the development of anogenital cancers. This study prospectively evaluated the diagnostic performance of the novel Allplex-HPV28 assay with the Anyplex-II-HPV28 to detect and genotype HPV in 234 consecutive swabs and 32 biopsies of the anogenital tract from 265 patients with atypical findings in cytomorphological screening. Agreement in HPV-DNA detection between the Anyplex-II and Allplex-HPV28 assays was 99%. There was a notable diversity in the HPV-virome, with the most prevalent high-risk HPV types being 16, 53, 66, and 68. The agreement rates for detecting these genotypes exceeded 93% between the Anyplex-II and Allplex-HPV28 assays. Discrepancies in test results were solely noted for Anyplex-II-HPV28 results with a low signal intensity of "+", and for Allplex-HPV28 results with cycle thresholds of ≥36. The semi-quantitative analysis of HPV-DNA loads showed significant agreement between the Anyplex-II-HPV28 and Allplex-HPV28 assays (p < 0.001). Furthermore, HPV-DNA detection rates and mean HPV-DNA loads significantly correlated with the grade of abnormal changes identified in cytopathological assessment, being highest in cases of HSIL, condyloma accuminatum, and squamous cell carcinoma. Overall agreement rates for detecting specific HPV-types among the Anyplex-II and Allplex-HPV28 assays exceeded 99.5% in cases of atypical squamous cells, condyloma accuminatum, and squamous cell carcinoma. The novel Allplex-HPV28 assay shows good diagnostic performance in detecting and genotyping HPV commonly associated with anogenital cancers. Consequently, this assay could offer substantial potential for incorporation into future molecular screening programs for anogenital cancers in clinical settings.

Analytical evaluation of the automated genotyping system (GenPlex) compared to a traditional real-time PCR assay for the detection of high-risk human papillomaviruses.

The detection of high-risk human papillomaviruses (HPVs) is crucial for early screening and preventing cervical cancer. However, the substantial workload in high-level hospitals or the limited resources in primary-level hospitals hinder widespread testing. To address this issue, we explored a sample-to-answer genotyping system and assessed its performance by comparing it with the traditional real-time polymerase chain reaction(PCR) method conducted manually. Samples randomly selected from those undergoing routine real-time PCR detection were re-analyzed using the fully automatic GenPlex® system. This system identifies 24 types of HPV through a combination of ordinary PCR and microarray-based reverse hybridization. Inconsistent results were confirmed by repeated testing with both methods, and the κ concordance test was employed to evaluate differences between the two methods. A total of 365 samples were randomly selected from 7259 women. According to real-time PCR results, 76 were high-risk HPV negative, and 289 were positive. The GenPlex® system achieved a κ value greater than 0.9 (ranging from 0.920 to 1.000, p < 0.0001) for 14 types of high-risk HPV, except HPV 51 (κ = 0.697, p < 0.0001). However, the inconsistent results in high-risk HPV 51 were revealed to be false positive in real-time PCR by other method. When counting by samples without discriminating the high-risk HPV type, the results of both methods were entirely consistent (κ = 1.000, p < 0.0001). Notably, the GenPlex® system identified more positive cases, with 73 having anHPV type not covered by real-time PCR, and 20 potentially due to low DNA concentration undetectable by the latter. Compared with the routinely used real-time PCR assay, the GenPlex® system demonstrated high consistency. Importantly, the system's advantages in automatic operation and a sealed lab-on-chip format respectively reduce manual work and prevent aerosol pollution. For widespread use of GenPlex® system, formal clinical validation following international criteria should be warranted.

HPV-Related Oropharyngeal Cancer in Southern Thailand: Proportion Trend and Survival Outcome.

Persistent high-risk human papillomavirus (HPV) infection is one of the major etiologies of oropharyngeal squamous cell carcinoma (OPSCC). This study aimed to determine the proportion, temporal trend, and prognostic significance of HPV-related OPSCC in Thai patients. The study included patients with OPSCC who were treated at Songklanagarind Hospital (Songkhla, Southern Thailand) from 2009 to 2020. HPV status was screened by p16 expression using immunohistochemistry and confirmed by real-time polymerase chain reaction. Cox regression was used to determine prognostic significance. The overall proportion of HPV+ OPSCC was 15.3% (95% confidence interval [CI]: 12.1-18.5) with a slightly increased proportion from 10.6% in 2009-2010 to 16.5% (2019-2020) (P for trend = 0.166). Among the HPV+ cases, HPV16 was detected in 65.3%, HPV18 in 34.7%, and other high-risk HPV types in 24%. Patients with P16+ or HPV+ OPSCC had significantly better overall survival (hazard ratio [HR]: 0.63, 95% CI: 0.45-0.90 and HR: 0.63, 95% CI: 0.45-0.88, respectively). Thai patients in the southern region have a low proportion of HPV-related OPSCC with an increasing trend. Both P16 expression and HPV DNA status are strong independent prognostic factors of OPSCC.

Multiple Anogenital Cancers in a 26-Year-Old Female: A Case Report

High-risk Human Papillomavirus (HPV) infections cause squamous intraepithelial lesions which act as precursors to invasive cancers. Due to the integration of HPV into host DNA, patients who have been diagnosed with HPV-associated invasive or preinvasive tumors may have a five-to-ten-fold increased risk of a second HPV-associated cancer, with a particularly strong association between anal and vulvovaginal cancers. This is a case report of a 26-year-old HIV-negative nulliparous female who developed independent squamous cell cancers of the vulvar, vaginal, cervix, and anus within a 2-year time frame in Cameroon. HPV specimens collected from the vagina and anus, and genotyped using the AmpFire HPV analyzer, revealed the presence of HPV Types 33, 51, and 68. Worldwide, HPV types 16 and 18 have been noted as the most virulent HPV types. Neither of these types was present in this patient with aggressive HPV-associated cancers. It is not known if the combination of these three types; 33, 51, and 68 forms a particularly virulent association in this population. This case demonstrates the importance of investigating less common high-risk HPV types and associated pathologies in this population. HPV genotypes other than 16 and 18 may play a significant role in cancer development in this population.

A case of coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), usual-type adenocarcinoma, and squamous cell carcinoma in situ of the cervix

Poorly differentiated adenosquamous carcinoma (glassy cell carcinoma) of the cervix is extremely rare, accounting for 1–2% of all cervical cancers. Herein, we report a case with coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), “usual-type” adenocarcinoma, and squamous cell carcinoma in situ of the cervix. A female patient in her 60 s was referred to our hospital and diagnosed with poorly differentiated adenosquamous carcinoma based on cervical cytology and biopsy. The tumor was classified as clinical stage IB1 cervical cancer following magnetic resonance imaging; radical hysterectomy was performed. Histopathological examination revealed poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), usual-type adenocarcinoma, and squamous cell carcinoma in situ, all coexisting. All carcinoma regions showed identical sizes to high-risk human papillomavirus (HPV) in fragment analysis. The patient is currently alive, without evidence of recurrence, 31 months post surgery. In this case, three different carcinomas coexisted. Fragment analysis of the patient’s HPV status suggested that all carcinomas were related to an infection with the same high-risk HPV type. To determine the precise mechanism of tumor development, i.e., whether the tumors were of the mixed or collision type, further studies are needed, including clonal analysis for the loss of heterozygosity pattern.

Interest of high-risk HPV typing by hybrid capture 2 in severe cervical dysplasias (CIN2/3) in Algeria

Persistent infection with high-risk human papillomavirus (HR-HPV) is the leading cause of cervical precancerous lesions and cervical cancer. The aim of the study was to evaluate the prevalence of high-risk HPV (HR-HPV) types among women with cervical intraepithelial neoplasia (CIN 2-3) and to evaluate the interest of high-risk HPV typing by hybrid capture 2 (HC2) in severe cervical dysplasias. 110 women were subjected to cyto-histological diagnostics and to the HPV test by HC2. The HC2 performance tests included Chi 2. Our results showed that the average age at the gynecological consultation in relation to cervical lesions was 38.75 ± 9.59 (22-72 years). The overall prevalence of HPV infection was 41.8%. High-risk HPV (HR-HPV) was detected in 31.8% of the total patients. In comparison with the other cytopathological stages, the HC2 test made it possible to evaluate the rate of HR-HPV at the CIN2/3 stage at 86% (p&lt;0.0061). In conclusion the prevalence of HR-HPV associated with cervical lesions is comparable to those in the literature. HC2 Allows good detection of HR-HPV in severe cervical dysplasias and can be used to compensate for the absence of vaccines in our country.

Coinfection of HPVs Is Associated with Advanced Stage in Colorectal Cancer Patients from Qatar

High-risk human papillomaviruses (HPVs) are considered risk factors in the origin of several human malignancies, such as breast, cervical, head and neck, as well as colorectal cancers. However, there are no data reported on the HPV status in colorectal cancer in the State of Qatar. Therefore, we herein examined the presence of high-risk HPVs (16, 18, 31, 33, 35, 45, 51, 52, and 59), using polymerase chain reaction (PCR) in a cohort of 100 Qatari colorectal cancer patients, and their association with tumor phenotype. We found that high-risk HPV types 16, 18, 31, 35, 45, 51, 52, and 59 were present in 4, 36, 14, 5, 14, 6, 41, and 17% of our samples, respectively. Overall, 69 (69%) of the 100 samples were HPV positive; among these, 34/100 (34%) were positive for single HPV subtypes, while 35/100 (35%) of the samples were positive for two or more HPV subtypes. No significant association was noted between the presence of HPV and tumor grade, stage, or location. However, the presence of coinfection of HPV subtypes strongly correlated with advanced stage (stage 3 and 4) colorectal cancer, indicating that the copresence of more than one HPV subtype can significantly worsen the prognosis of colorectal cancer. The results from this study imply that coinfection with high-risk HPV subtypes is associated with the development of colorectal cancer in the Qatari population.

Correlation Between E6 and E7 Oncogene Mutation Human Papilloma Virus High Risk Type 16 with Retinoblastoma Protein Expression in Cervical Cancer

Introduction: The E6 and E7 oncoproteins of high-risk Human Papillomavirus (HPV) have crucial roles in cervical cancer pathogenesis by inhibiting p53 and retinoblastoma protein (pRb) which are tumor suppressor genes. Genetic sequence mutations of E6 and E7 oncogenes can affect E6/E7 protein functions that will change E7-pRB interaction. Furthermore, this condition will influence progression cervical cancer progression in several intratypic variants of high-risk HPV type 16. Methods: A cross-sectional study was conducted from September 2020-September 2021, at the Obstetrics and Gynecology Outpatient Clinic, Prof Dr I. G. N. G. Ngoerah General Hospital. Consecutive sampling was taken by collecting cervical cancer tissue followed by isolation, amplification, and gene sequencing to assess E6 and E7 mutations. The expression of pRb was measured by immunohistochemical staining (IHC). Results: From 100 cervical cancer subjects, 31 subjects were found HPV16 positive (19 wildtype and 12 mutants). The proportion of E6 and E7 mutants was 25.8% and 12.9% respectively. This study shows that T27C/F9F; A360G/E120E and G371A/R124K variants were found on E6 oncogene mutations, meanwhile, A86C/N29T; A86G/N29S; C229T/R77C and T285C/S95S variants were detected on E7 oncogene mutations. The types of E6 mutations were T27C (16.1%), A360G (6.4%) and G371A (1 subject; 3.2%). In addition, pRb expression was stronger in mutant group than wild-type group 60.5% vs. 53%. There was no correlation between retinoblastoma protein expression and mutations E6/E7 oncogene HPV Type 16 (PR 0.22; 95% CI 0.03-1.6; p value 0.10). Conclusions: In cervical cancer, there is no significant difference between the expression of retinoblastoma protein in mutant vs wildtype E6 and E7 oncogene HPV16.

Abstract 2442: Seminal fluid enhances cervical squamous carcinoma cell proliferation, epithelial mesenchymal transition (EMT), migration &amp; invasion

Abstract Cervical cancer is the leading cause of cancer related deaths &amp; the second most common cancer amongst South African women. Though there are various risk factors, the most common risk factor for cervical cancer development is sexual transmission &amp; persistent infection with high-risk Human Papillomavirus (HPV). Although most HPV infections are cleared naturally in women, persistent infection with high-risk HPV types promotes neoplastic transformation &amp; tumorigenesis. Furthermore, exposure of neoplastic cervical epithelial cells to inflammatory mediators may drive the progression of cervical cancer. Seminal fluid (SF), a biological fluid rich in inflammatory mediators &amp; growth factors, has been implicated in cervical cancer progression. SF has been shown to induce the expression of proinflammatory mediators which promotes cell proliferation in culture &amp; growth of explants in mice injected with HeLa cervical adenocarcinoma cells. Since majority of cervical cancer cases are squamous cell carcinoma, in this study, we examined the effect of SF on cell proliferation, EMT, cell migration &amp; invasion employing SiHa and Me180 squamous cell carcinoma cell lines. Our results showed that SF significantly enhanced cell proliferation in both cell lines. Using Confocal microscopy and phalloidin staining we further showed that SF caused morphological changes and stress fibre formation. RT-qPCR showed that SF up regulated EMT transcription factors Snail, ZEB1 &amp; TWIST mRNA expression. EMT induction was further confirmed by the increase of N-cadherin &amp; a subsequent decrease in E-cadherin protein expression. Additionally, we showed that the induction of EMT transcription factors by SF occurs via the EGF/ERK/COX pathway. To investigate the effect of SF on migration and invasion, transwell migration assays were used. Results showed that SF significantly enhanced cell migration &amp; invasion of the SiHa and Me180 cells. Our results show that SF plays a role in enhancing the migratory &amp; invasive potential of squamous cell carcinoma cells &amp; that this associates with increased expression of EMT transcription factors. These findings together implicate SF as a possible factor that may promote cervical cancer progression. Citation Format: Nonkululeko Mkwanazi, Virna D. Leaner, Arieh A. Katz. Seminal fluid enhances cervical squamous carcinoma cell proliferation, epithelial mesenchymal transition (EMT), migration &amp; invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2442.

Clinical Validation of the Fully Automated NeuMoDx HPV Assay for Cervical Cancer Screening.

The NeuMoDx HPV assay is a novel fully automated, real-time PCR-based assay for the qualitative detection of high-risk human papillomavirus (HPV) DNA in cervical specimens. The assay specifically identifies HPV16 and HPV18 and concurrently detects 13 other high-risk HPV types at clinically relevant infection levels. Following the international guidelines, the clinical performance of the NeuMoDx HPV assay for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) against the reference standard Hybrid Capture 2, as well as intra- and inter-laboratory reproducibility were assessed on PreservCyt samples. The clinical accuracy of the assay was additionally evaluated against the clinically validated Alinity m HR HPV and COBAS 4800 HPV Test on PreservCyt samples, and against the clinically validated HPV-Risk assay on SurePath samples. The NeuMoDx HPV assay performance for CIN2+ was non-inferior to the reference methods on both sample types (all p < 0.05), and showed excellent intra- and inter-laboratory reproducibility (95.7%; 95% CI: 93.9–97.3; kappa value 0.90 (95% CI: 0.86–0.94); and 94.5%; 95% CI: 92.6–96.2; kappa value 0.87 (95% CI: 0.82–0.92), respectively). In conclusion, the NeuMoDx HPV assay meets international guideline criteria for cross-sectional accuracy and reproducibility, and performs equally well on cervical screening specimens collected in two widely used collection media. The NeuMoDx HPV assay fulfils the requirements to be used for primary cervical screening.

Immunomolecular Investigation of Human Papillomavirus Genotypes (16, 18) and P63 Expression in Patients with Malignant and Non-malignant Colorectal Tumors.

Cancer of the colon (colorectal cancer, or CRC) is the third most frequent malignancy in the world and the fourth leading cause of cancer-related death. Recent research has focused on the link between high-risk human papillomavirus (HPV) infections and the onset/development of several different types of cancer in humans. As a result, scientists are now paying more attention to HPV and CRC. In a variety of malignant tumors, P63 is overexpressed. This includes non-Hodgkin lymphoma and breast carcinoma, as well as lung, bladder, and prostate cancers. However, in accordance with the existence of many P63 isoforms in malignant tumors, the actions of P63 in these malignancies remain a source of debate. P63 immunohistochemistry expression in CRC tissues is being investigated as a possible etiological link between high-risk HPV types and CRC. This retrospective study intended to investigate if there was an etiological link between high-risk HPV types and CRC. It has utilized 92 chosen formalin-fixed and paraffin-embedded tissue block samples. The collected samples were divided into 62 blocks of colorectal adenocarcinoma mass tissues and 30 non-malignant colorectal tissues used as a control group. Chromogenic in situ hybridization (CISH) was employed to discover HPV DNA16/18 in colorectal tissues. The overall proportion of positive HPV16/18 DNA- CISH detection in the mass CRC group was 44.4%, whereas HPV16/18 DNA was obtained at 80.0% in the non-malignant control group. The overall proportion of positive P63-ISH detection in the CRC group was also 70.4%, whereas P63 was 73.3% in the non-malignant control group. The link between HPV infection and P63 expression in CRC might point to the importance of these molecules in the progression of CRC.

The effect of other high-risk HPV types on cervical intraepithelial neoplasia and cancer

Objective: Cervical cancer is an serious healthcare problem with a high mortality rate. High-risk Human papillomavirus (HPV) geno-types, especially HPV 16, 31, 33, and 18, are the leading cause of cervical cancer and cervical intraepithelial neoplasia. Cervical cancer screening programs, especially ones that are HPV-based, have gained prominence in many countries. Herein, we evaluated the effect of other high-risk (hr) HPV types (HPV 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) with normal cytology on cervical intraepithelial neoplasia and cancer. Methods: 9015 patients were screened via HPV typing and cytology. 520 patients with high-risk HPV positivity, aged 25–65, and unvaccinated for HPV were included in the study. Patients with high-risk HPV DNA positivity and cytologic abnor-mality, HPV 16–18 positivity, or with high-risk HPV DNA positivity and normal cytology or with postcoital bleeding and/or suspicious appearance of the cervix underwent colposcopy and colposcopic-directed biopsy. Results: Of the 520 women included in the study, the prevalence of the hr-HPV types is as follows: HPV 16 (29%), HPV 18 (13.7%), other high-risk HPV (43.8%), and HPV 16 or 18 plus other hr-HPV (13.5%). Among patients diagnosed with ≥ CIN2, 36.3% had HPV 16 positivity, 21.8% had HPV 18, 24.2% had other hr-HPV and 17.7% had co-infection with HPV type 16 and 18 and other hr-HPV types. HPV 16 (Odds Ratio (OR) = 3.099, 95%Confidence Interval (CI) = 1.933–4.968), HPV 18 (OR = 4.834, 95% CI = 2.715–8.608), and co-infection with HPV 16 or 18 with other hr-HPV types (OR = 3.324, 95% CI = 1.851–5.969) were statistically significantly associated ≥ CIN2 on biopsy. Among patietns with normal cytology and positive for other hr-HPV types CIN2+ was detected in 10.3% of patients who underwent biopsy, but only 1.5%had CIN3 and no cancers were detected. Conclusion: Consistent with our national screening guidelines, the risk for CIN3+ for women with normal cytology but positive for hr-HPV types other than 16 and 18 is low. Re-testing these patients in one year appears acceptable.

Prevalence and genotype distribution of human papillomavirus infection among women aged 30–65 years in Xi’an, China: a population-based study of 14,655 women

ABSTRACT Cervical cancer is the fourth most common cancer among women worldwide in terms of both incidence and mortality. Persistent infection with high-risk human papillomavirus (HPV) has been identified as a cause of cervical intraepithelial neoplasia and invasive cervical cancer. The distribution of human papillomavirus genotypes varies regionally. To acquire baseline data on the population-based prevalence and genotype distribution of HPV infection, we investigated the molecular epidemiology of HPV infection among women in Xi’an, China. The study was conducted from September 2018 to December 2020. A total of 14,655 women aged 30–65 years were screened. The overall prevalence of HPV infection was 13.5% (95% confidence interval [CI]: 13.0–14.1%), with 10.4% of participants being positive for a single HPV type and 3.1% being positive for multiple HPV types. The prevalence of high-risk HPV (HR-HPV), low-risk HPV (LR-HPV) and mixed HPV infection was 10.1% (95% CI: 9.6–10.5%), 2.2% (95% CI: 2.0–2.4%), and 1.3% (95% CI: 1.1–1.5%), respectively. The five most frequently detected HR-HPV types were types 52 (2.6%), 16 (1.9%), 53 (1.8%), 58 (1.4%), and 51 (0.9%). The most frequently detected LR-HPV type was HPV-42 (1.1%). The prevalence and HPV genotype distribution varied by region and age. Age-specific HPV prevalence peaked in the over 60 years age group (18.8%), and Beilin District had the highest HPV prevalence (18.1%). The results of this first population-based study provide a reference for HPV-based cervical cancer screening and HPV vaccination programs in Xi’an.

High-risk human papillomavirus (HPV) detection in formalin-fixed paraffin-embedded cervical tissues: performances of Aptima HPV assay and Beckton Dickinson (BD) Onclarity assay

AimThere are many scenarios where high-risk human papillomavirus (HPV) detection in formalin-fixed paraffin-embedded (FFPE) specimens is important. However, there is no Food and Drug Administration (FDA)-approved and clinically validated technique...

Prevalence and genotype distribution of high-risk HPV infection among women in Beijing, China.

Cervical cancer (CC) is highly associated with high-risk human papillomavirus (HPV) infection and genotype distribution of high-risk HPV (HR-HPV) infection varies greatly in different regions. Clinical specimens were collected from 46 365 patients at Beijing Friendship Hospital, Capital Medical University from January 2017 to December 2020. HPV DNA genotype testing was performed using real-time PCR. The infection rates based on disease group were compared using the χ 2 test. The linear-by-linear association test and gamma value were used to assess the changes in HPV prevalence over calendar year and age group. A total of 10 514 women were infected with HR-HPV, with an overall positive rate of 22.7%. The most prevalent HR-HPV types were HPV52, 58, 16, 51, and 66, and HPV59 had a higher prevalence except for HPV16, 58, and 52 in the CC group. Single infection of HR-HPV was dominant among different disease groups. The infection rate of HR-HPV decreased first and then increased from below 20 years old to over 60 years old. There were significant differences in the HR-HPV infection rates among the age and disease groups. Our findings demonstrate that the genotype distribution of HR-HPV varied with age and diseases. The HR-HPV genotypes prevalence was found to be directly useful for local governments to promote HPV targeted vaccination in the study region.

Oncoproteins of High-Risk HPV and EBV Cooperate to Enhance Cell Motility and Invasion of Human Breast Cancer Cells via Erk1/Erk2 and β-Catenin Signaling Pathways.

Breast cancer is a leading cause of death in women around the world. Most breast cancer-related deaths are a result of complications from the metastatic spread. Several recent studies reported that high-risk human papillomaviruses (HPVs) and Epstein–Barr virus (EBV) are co-presented in different types of human carcinomas including breast; however, the cooperative effects between high-risk HPVs and EBV oncoproteins in human breast cancer have not been investigated yet. Thus, we herein explored the cooperation outcome between E6/E7 and latent membrane protein 1 (LMP1) oncoproteins of high-risk HPV type 16 and EBV, respectively, in two human breast cancer cell lines, MCF7 and MDA-MB-231. Our data revealed that the cooperation of E6/E7 and LMP1 oncoproteins stimulates cell proliferation and deregulates cell cycle progression of human breast cancer and normal mammary cells; in parallel, we noted that E6/E7/LMP1 incite colony formation of both breast cancer cell lines but not normal cells. More significantly, our results point out that the co-expression of E6/E7 and LMP1 oncoproteins enhances cell motility and invasion of MCF7 and MDA-MB-231 cell lines; this is accompanied by deregulation of epithelial–mesenchymal transition biomarkers including E-cadherin, β-catenin, fascin, and vimentin. The molecular pathway analysis of HPV and EBV oncoproteins cooperation shows that it can enhance the phosphorylation of extracellular signal-regulated kinases (Erk1/Erk2) in addition to β-catenin, which could be behind the effect of this cooperation in our cell models. The study clearly suggests that high-risk HPV and EBV coinfection can play an important role in breast cancer progression via Erk1/Erk2 and β-catenin signaling pathways.

High-Risk Human Papillomaviruses in Oral Squamous Cell Carcinoma (OSCC): A Meta-Analysis

Background: The prevalence of high-risk Human Papillomaviruses (HPV) in cases of oral cavity squamous cell carcinoma (OSCC) varies widely. Therefore, the aim of this study was to determine the pooled prevalence of all high-risk HPV by meta-analysis with specific emphasis on HPV type 16/18. Methods: The studies were retrieved from PubMed and MEDLINE to conduct a comprehensive literature review on HPV detection in OSCC. Search terms included, High-risk HPV, oral cancer, polymerase chain reaction (PCR), in situ hybridization (ISH). We reviewed 47 research studies systematically to report the prevalence of high-risk HPV infection in oral cancer. Included studies published from 1988 to 2018. The meta-analysis was carried out by using MedCalc software version 19.0.3. Results: A meta-analysis was executed to calculate the pooled prevalence of High-risk HPV types, which revealed overall decreasing order frequency of high-risk HPV and high-risk type displaying the highest number of type16/18 HPV in the reported cases. As 30.71% [24.59 to 37.19 % confidence interval (CI) at 95%] and 28.88 % [22.62 to 35.57% confidence interval (CI) at 95%] followed by other high-risk HPV 3.59% [2.22 to 5.46%] respectively. Conclusions: According to present meta-analysis, we conclude that 16/18 HPV displaying maximum infection rate as compared to other high-risk HPV type in OSCC cases.

Genomic and human papillomavirus profiling of an oral cancer cohort identifies TP53 as a predictor of overall survival

AbtractBackgroundThe genomic landscape of head and neck cancer has been reported through The Cancer Genome Atlas project. We attempt to determine if high-risk human papillomavirus (HPV) or frequently mutated genes are correlated with survival in an oral cancer cohort.MethodsPatient demographic data along with data from final pathology was collected. Tumor DNA was analyzed using a custom Illumina targeted sequencing panel. Five high-risk HPV types were tested by qPCR. Statistical analyses were used to identify associations between patient outcome and mutational status.ResultsHigh-risk HPV types were identified in 7% of cases; HPV status was not associated with survival. Mutations were identified in TP53, TERT promoter, & PIK3CA. Mutations in TP53 were significantly associated with poorer overall survival on multi-variate analysis (p = 0.03).ConclusionsMutations in TP53 were associated with poor patient survival. Expanding our sample size may identify further predictors of outcome to direct customized cancer care.

High-risk human papillomavirus infection in female and subsequent risk of infertility: a population-based cohort study

To study whether infection with high-risk human papillomavirus (HPV), registered both as a single HPV positive test and as HPV persistence, increases the risk of female factor infertility in later reproductive life. Population-based cohort study. Not applicable. A random sample of 11,088 women (20-29years of age at enrollment) tested for cervical HPV at enrollment during 1991-93 and again after 2years. Information on female factor infertility was obtained by linkage to the Danish Infertility Cohort. None. Follow-up for each study participant was the period from the date of enrollment or date of the second visit until diagnosis of female factor infertility (main outcome), conception, death, emigration, disappearance, or end of study period. Data were analyzed by means of a Cox proportional hazards regression model. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HPV status and female factor infertility after adjustment for potentially confounding factors were determined. After relevant exclusions, 10,595 women were eligible for analysis, 1,861 (17.6%) of whom were high-risk HPV positive at the first visit. There was no association between a positive HPV test at first visit (HR = 0.88; 95% CI, 0.75-1.02) or positivity for the same high-risk HPV type at the first and second visit (persistence; HR = 0.97; 95% CI, 0.66-1.44) and subsequent risk of female factor infertility in reproductive life. We found no association between a high-risk HPV infection and risk of female factor infertility, neither for a single HPV positive test nor for a persistent HPV infection.

Fast approximate computation of cervical cancer screening outcomes by a deterministic multiple-type HPV progression model

Cervical cancer arises differentially from infections with up to 14 high-risk human papillomavirus (HPV) types, making model-based evaluations of cervical cancer screening strategies computationally heavy and structurally complex. Thus, with the high number of HPV types, microsimulation is typically used to investigate cervical cancer screening strategies. We developed a feasible deterministic model that integrates varying natural history of cervical cancer by the different high-risk HPV types with compressed mixture representations of the screened population, allowing for fast computation of screening interventions. To evaluate the method, we built a corresponding microsimulation model. The outcomes of the deterministic model were stable over different levels of compression and agreed with the microsimulation model for all disease states, screening outcomes, and levels of cancer incidence. The compression reduced the computation time more than 1000 fold when compared to microsimulation in a cohort of 1 million women. The compressed mixture representations enable the assessment of uncertainties surrounding the natural history of cervical cancer and screening decisions in a computationally undemanding way.