High-risk Oncogenic Human Papillomavirus Research Articles

Tumor Typing of Endocervical Adenocarcinoma: Contemporary Review and Recommendations From the International Society of Gynecological Pathologists.

The incidence of endocervical adenocarcinoma, the second most common cervical cancer in the world, has been on the rise. While most cervical cancers are squamous cell carcinomas and associated with high-risk oncogenic human papillomavirus (HPV), approximately 15% of endocervical adenocarcinomas, which now represent about one quarter of all cervical cancers, are HPV-independent. In this review, we will focus on the shortcomings of historical histologic classification systems of female genital tract tumors as they pertain to endocervical adenocarcinomas, and we will highlight the advantages of the new International Endocervical Adenocarcinoma Criteria and Classification system, which forms the basis for the WHO 2020 classification. We will cover the various histologic types, subtypes, and variants of endocervical adenocarcinoma with regard to morphology, immunophenotype, molecular genetics, HPV status and differential diagnosis, and we will provide International Society of Gynecological Pathologists recommendations for diagnosing these tumors.

MEK/ERK signaling is a critical regulator of high-risk human papillomavirus oncogene expression revealing therapeutic targets for HPV-induced tumors.

Intracellular pathogens have evolved to utilize normal cellular processes to complete their replicative cycles. Pathogens that interface with proliferative cell signaling pathways risk infections that can lead to cancers, but the factors that influence malignant outcomes are incompletely understood. Human papillomaviruses (HPVs) predominantly cause benign hyperplasia in stratifying epithelial tissues. However, a subset of carcinogenic or “high-risk” HPV (hr-HPV) genotypes are etiologically linked to nearly 5% of all human cancers. Progression of hr-HPV-induced lesions to malignancies is characterized by increased expression of the E6 and E7 oncogenes and the oncogenic functions of these viral proteins have been widely studied. Yet, the mechanisms that regulate hr-HPV oncogene transcription and suppress their expression in benign lesions remain poorly understood. Here, we demonstrate that EGFR/MEK/ERK signaling, influenced by epithelial contact inhibition and tissue differentiation cues, regulates hr-HPV oncogene expression. Using monolayer cells, epithelial organotypic tissue models, and neoplastic tissue biopsy materials, we show that cell-extrinsic activation of ERK overrides cellular control to promote HPV oncogene expression and the neoplastic phenotype. Our data suggest that HPVs are adapted to use the EGFR/MEK/ERK signaling pathway to regulate their productive replicative cycles. Mechanistic studies show that EGFR/MEK/ERK signaling influences AP-1 transcription factor activity and AP-1 factor knockdown reduces oncogene transcription. Furthermore, pharmacological inhibitors of EGFR, MEK, and ERK signaling quash HPV oncogene expression and the neoplastic phenotype, revealing a potential clinical strategy to suppress uncontrolled cell proliferation, reduce oncogene expression and treat HPV neoplasia.

Knowledge, Attitude, and Practice on Cervical Cancer Screening and Associated Factors Among Women Aged 15-49 Years in Adigrat Town, Northern Ethiopia, 2019: A Community-Based Cross-Sectional Study.

BackgroundCervical cancer, mainly attributed to persistent infection with a high-risk oncogenic human papillomavirus (HPV), is one of the most common types of women’s cancer globally, with more than 90% of new cases occurring in developing and resource-limited countries. In Ethiopia, cervical cancer ranks as the most frequent cancer among women and cause for 4732 deaths annually.ObjectiveTo assess knowledge, attitude, practice towards screening on cervical cancer and associated factors among women aged 15–49 years in Adigrat town, northern Tigray Ethiopia.MethodsA community based quantitative study design was conducted among 617 samples in Adigrat town, northern Tigray Ethiopia. Data were collected using a structured, semi-structured, and pre-tested questionnaire. Associations between dependent and independent variables were tested using logistic regression with the assumptions of p-values <0.05 and confidence interval 95% and considered to be statistically significant.ResultsThis study indicated that 46.4%, 53.3%, 38.1% of participants had knowledge, positive attitude, and screened on cervical cancer, respectively. Diploma and above [AOR=3.7, 95% CI (1.443, 9.433) were significant factors associated with knowledge of cervical cancer screening utilization. Primary school (1–8) [AOR=2.7, 95% CI (1.297, 5.699)], greater than 500 ETB household income [AOR = 4.8, 95% CI (2.783, 8.577)] were significant factors associated with attitude of cervical cancer screening utilization. Secondary school (9–12) [AOR = 3.4, 95% CI (1.565, 7.458)], not knowledgeable of cervical cancer [AOR = 1.8, 95% CI (1.156, 2.698)] were significant factors associated with practice of cervical cancer screening utilization.ConclusionFactors like age, educational status, anyone knowing with cervical cancer and ever received cancer information had a significant association with knowledge of cervical cancer screening utilization. Educational status and perceived income of the household had a significant association with an attitude of cervical cancer screening utilization. Educational status perceived income of the household, anyone knowing with cervical cancer, ever received cancer information, and knowledge of cervical cancer screening utilization were predictors of cervical cancer screening practice.

Bioinformatics analysis of putative causes for сross-reactive antibodies interacting with antigens derived from various pathogenic human papillomaviruses

Human papillomaviruses (HPVs) belong to highly abundant resulting in sexually transmitted virus infections, and cause cervical cancer holding place 4 among most common cancer types in women. In 2012, there were registered 266,000 death cases and 528,000 new cases. At present, three HPV prophylactic vaccines were generated worldwide: bivalent Cervarix, quadrivalent Gardasil and nonavalent Gardasil-9. Examining such vaccines uncovered that they are able to induce anti-HPV antibody production against viral antigens lacked in vaccine formula. The mechanism of such crossneutralizing antibodies recognizing antigens derived from various HPV pathogenic types remains unknown. In our study we attempted to uncover putative basis underlying cross-reactive interaction between vaccine-induced antibodies and non-vaccine antigens by bioinformatical approaches, that might allow optimize generation of future candidate vaccines and obtain more effective polyvalent immunobiological preparations against HPV. We used amino acid sequences of L1 coat protein of four top high-risk oncogenic HPV types (16, 18, 31 and 45) in the study. Work sequences were retrieved from the International Data Base of NCBI (National Center for Biotechnology Information) and aligned by using Clustal Omega’ and BioEdit software. A search and analysis of distinct antigenic determinant (epitopes) were performed by using software suite BepiPred-2.0: Sequential B-Cell Epitope Predictor, DiscoTope 2.0 Server, and SYFPEITHI. Bioinformatics data revealed pronounced potential of cross-neutralizing vaccine-induced antibodies and non-vaccines antigens derived from high-risk pathogenic types HPV 16, 18, 31 and 45 owing to the similarity in antigenic determinants (epitopes). Common linear determinants for T- and B-cells were found in all four types of L1 protein counterparts. In addition, similar three-dimensional B-cell determinants were discovered in HPV16 L1 and HPV18 L1. Antigenic determinants derived from HPV16 L1 and HPV31 L1 exhibited most close similarity. Hence, while immunizing with HPV16 L1, a more pronounced and moderate cross-reactive antibodies interacting with HPV31 L1 as well as HPV18 L1 and HPV45 L1 antigens, respectively, should be expected. Inversely, immunization with HPV18 L1might elicit active and less efficient crossneutralizing response with HPV45 L1 as well as HPV16 L1 and HPV31 L1, respectively.

Prevalence of high risk human papilloma virus among Iraqi women with abnormal cervical cytology

Persistent infection with high-risk human papilloma virus (HPV) has been recognized as the primary etiological agent for the development of premalignant and malignant cervical lesions. Cervical cancer represents a major health problem among female especially in developing countries. This study was designed to determine the prevalence of oncogenic HPV genotypes among Iraqi women who had abnormal cytological findings by using endpoint multiplex PCR. Fifty cervical swab specimens were collected from women complaining from gynecological problems and another thirty specimens obtained from apparently healthy women as a control group. Cytological examination showed that lesions in the forms of atypical squamous cells of undetermined significance (ASCUS), low grade squamous intraepithelial lesions (LSIL), high grade squamous intraepithelial lesions (HSIL), atypical squamous cells cannot exclude HSIL (ASC-H), non-specific cervicitis and squamous cervical cancer were observed in 30%, 24%, 20%, 4%, 16% and 6%, respectively. High-risk HPV DNA was detected in 19% among women population with the oncogenic HPV-16, -18 and -58 were being the most prevalent high risk genotypes among women at frequencies of 26.7%, 13.3% and 13.3%, respectively. The detection of high-risk HPV and its association with the ASC-US lesions may serve as a prognostic factor prior to cervical cancer disease progression.

Long-term follow-up of human papillomavirus type replacement among young pregnant Finnish females before and after a community-randomised HPV vaccination trial with moderate coverage.

Large scale human papillomavirus (HPV) vaccination against the most oncogenic high-risk human papillomavirus (HPV) types 16/18 is rapidly reducing their incidence. However, attempts at assessing if this leads to an increase of nonvaccine targeted HPV types have been hampered by several limitations, such as the inability to differentiate secular trends. We performed a population-based serological survey of unvaccinated young women over 12 years. The women were under 23-years-old, residents from 33 communities which participated in a community-randomised trial (CRT) with approximately 50% vaccination coverage. Serum samples were retrieved pre-CRT and post-CRT implementation. Seropositivity to 17 HPV types was assessed. HPV seroprevalence ratios (PR) comparing the postvaccination to prevaccination era were estimated by trial arm. This was also assessed among the sexual risk-taking core group, where type replacement may occur more rapidly. In total, 8022 serum samples from the population-based Finnish Maternity Cohort were retrieved. HPV types 16/18 showed decreased seroprevalence among the unvaccinated in communities only after gender-neutral vaccination (PR16/18A = 0.8, 95% CI 0.7-0.9). HPV6/11 and HPV73 were decreased after gender-neutral vaccination (PR6/11A = 0.8, 95% CI 0.7-0.9, PR73A = 0.7, 95% CI 0.6-0.9, respectively) and girls-only vaccination (PR6/11B = 0.8, 95% CI 0.7-0.9, PR73B = 0.9, 95% CI 0.8-1.0). HPV68 alone was increased but only after girls-only vaccination (PR68B = 1.3, 95% CI 1.0-1.7, PRcore68B = 2.8, 95% CI 1.2-6.3). A large-scale, long-term follow-up found no type replacement in the communities with the strongest reduction of vaccine HPV types. Limited evidence for an increase in HPV68 was restricted to girls-only vaccinated communities and may have been due to secular trends (ClinicalTrials.gov number: NCT00534638).

Genotypes and Prevalence of High-Risk Human Papillomavirus Among Patients Diagnosed With Head and Neck Cancer at Alexandria Cancer Centre

PURPOSE The purpose of this study was to provide original data on the prevalence of head and neck cancer (HNC) and high-risk human papillomavirus (HPV) genotypes among patients diagnosed with HNC in Kenya. Globocan 2018 findings indicate that cervical cancer is the second most frequent cancer in women in East Africa, which suggests a high prevalence of oncogenic HPV among the general population in this region. METHODS This was a retrospective study with laboratory analysis involving histologically confirmed head and neck tissue samples between January 2017 and December 2018. Stored tissues were retrieved and subjected to repeat microscopy, p16 immunohistochemistry, and HPV polymerase chain reaction at the Pathologists Lancet Group of Laboratories. Data were analyzed using descriptive statistics with Excel. RESULTS HNC accounted for 8.8% of all malignancies at Alexandria Cancer and Palliative Care Hospital. There were more males (64%) than females (36%). Mean age was 50.9 years (± 17.6 years). Most patients came from the western Kenya region. Approximately one third (35.7%) of participants were farmers and students combined. The following were most common subsites identified: nasopharynx (n = 25), larynx (n = 12), and tongue (n = 10); 93.5% were squamous cell carcinoma. Sixteen samples (55.2%) tested p16 positive, of these 2 (12.5%) tested positive with HPV polymerase chain reaction. One of these was from an 87-year-old female who was diagnosed with tongue cancer. Molecular analysis revealed the genotype to be HPV52, and the other was from a 49-year-old male with cancer of the postnasal space who had multiple coinfection with HPV35, -52, and -59 genotypes. CONCLUSION HNC represented 8.8% of the malignancies at Alexandria Cancer and Palliative Care Hospital; 55.2% tested p16 positive and the study managed to detect 3 high-risk HPV genotypes, HPV35, HPV52, and HPV59.

Abstract A22: Cervical cancer immunomodulation through stat3 and p65 NFκb: Effects beyond the tumor microenvironment

Abstract Chronic signaling by molecules generated in the tumor microenvironment has local and systemic effects on the immune system. We have previously shown that cervical cancer cells express cytokines as IL-6 and G-CSF, among other factors. These cytokines have been associated with cancer progression in several types of cancer, either by promoting chronic inflammation and/or tolerance. Trying to better understand how cells from the immune system and tumor integrate signals generated by the tumor microenvironment, we have investigated the activation status of signaling pathways involved in cell proliferation and survival, inflammation and immune responses. We observed a cohort of cervical cancer patients, all of whom had cervical biopsies positive for high oncogenic risk human papillomavirus (HPV). In the cervical cancer biopsies, we found constitutive expression of phosphorylated STAT3, Akt, p65 NFκB and CREB, in both the tumor and leukocyte compartments. In the peripheral blood, however, we found constitutive expression of phosphorylated STAT3 and Akt, but significantly lower expression of phosphorylated p65 NFκB than in controls. Data previously published by our laboratory using a HPV16 experimental model showed high constitutive expression of phospho-STAT3 and low negative expression of phospho-p65 NFκB in splenocytes of tumor-bearing mice compared to controls. Given the data from our patients, we hypothesized that the high STAT3 expression and low NFκB expression could have a correlation, with a biologic effect on tumor-bearing subjects. Again, using an HPV16 experimental model, we neutralized IL-6 and G-CSF expression or pharmacologically inhibited STAT3 with the NSC74859 compound. In both cases, we observed significant reduction in tumor growth, decrease in phospho-STAT3 expression (when using the neutralizing antibodies), and importantly, significant increase in phospho-p65 NFκB expression. We also observed a significant increase in T-cell infiltration in tumors from treated animals and increase in antigen-specific T-cell proliferation. Our data indicate that cytokines that signal chronically through STAT3 can inhibit antitumor immune responses through NFκB inhibition. We also suggest that inhibition of STAT3 may be used as therapeutic tool against cervical cancer and other HPV-associated cancers. Financial support: FAPESP 2014/19326-6; 2008/57889-1; CNPq 573799/2008-3. Citation Format: Renata Ariza Marques Rossetti, Gretel Rodriguez Rodriguez, Ildelfonso Alves Da Silva, Jr. Jesus De Paula Carvalho, Maria Beatriz Sartor De Faria Rosa, Luisa Lina Villa, Ana Paula Lepique. Cervical cancer immunomodulation through stat3 and p65 NFκb: Effects beyond the tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr A22.

Detection Rates of Human Papillomavirus Associated with Cervical Cancer in Women of Nizhny Novgorod

The purpose of the study was to assess detection rates of human papillomavirus in cervical cancer cases of Nizhny Novgorod. Materials and methods. We used the real-time polymerase chain reaction (PCR) to test samples of mucosa lining of the cervical canal and/or transformation zone taken from 630 women with cervical dysplasia of different degrees and 107 incident cases of cervical cancer that did not undergo treatment. The detection and differentiation of 14 genotypes of high-risk human papillomaviruses (HPV) was carried out using the AmpliSens® HPV HCR-genotype-FRT PRC kit. Results. The overall infection rate of women with oncogenic human papillomaviruses was 41.8%. Among the genotypes, HPV 16 (39.2%), 18 (15.5%), 33 (16.6%), and 56 (11.9%) predominated. A high prevalence of oncogenic HPV was detected in the women with cervical intraepithelial neoplasia (58.1%) and cervical cancer (90%). The spectrum of genotypes in women with neoplasia of various degrees differed. In women with CIN II and CIN III, vaccine-preventable HPV genotypes (HPV 16 and 18) playing the leading role in the development of cervical cancer were the most frequent. The same genotypes dominated in the women with invasive cervical cancer. One oncogenic HPV genotype was usually found in the infected women (69%). The high-risk HPV infection was often combined with Ureaplasma ssp (49.3%), Mycoplasma hominis (20.1%), Cytomegalovirus (21.1%), and Herpes simplex I/II (18.2%) infections. Combinations of high-risk HPV with Chlamydia trachomatis and Herpes 6 were found in 8.3% and 5% of the cases, respectively. Conclusions. Our findings proved a wide prevalence of high carcinogenic risk HPV 16 and 18 genotypes, thus indicating the expediency of using Cervarix and Gardasil vaccines registered in the Russian Federation and containing antigens to these types of virus for specific prevention of the HPV infection.

Prevalence of Oncogenic Human Papillomavirus Genotypes Among Sexually Active Women in Parakou (Benin, West Africa)

Background: The genital infection due to Human papillomavirus (HPV) is considered as the most common sexually transmitted infection across the world, including high-risk oncogenic HPV (HR/HPV). Objective: This study aimed to determine the prevalence of HR/HPV genotypes among sexually active women in Parakou (Benin) in 2017. Methods: This research work was a cross-sectional descriptive study carried out in the city of Parakou (Benin), from January 15 to April 15, 2017. Sample consisted of 247 sexually active women selected through a systematic random sampling. Cervical specimens collected with swab were subject to multiplex PCR to characterize 14 HR/HPV genotypes. Results: The prevalence of HR/HPV infection was rated 32.8% [95% CI: 27.1-39.3]. All the fourteen HR/HPV genotypes investigated were detected using PCR among our study population. The most common types of HR/HPV were, in descending order, HPV45 (25.9%), HPV35 (18.5%), HPV52 (17.3%), HPV51 (16.0%) and HPV58 (14.8%). HPV16 and 18 were found out at respective proportions of 2.5% and 7.4%. Age group 20 years or less had the highest prevalence of HR/HPV infection (55.7%) followed by age group from 21 to 30 years (38.3%). Conclusion: The prevalence of HR/HPV infection is high among sexually active women in Parakou in 2017 and the most frequent HR/HPV are not those found commonly in precancerous and cancerous cervical lesions.

Исследование наличия ДНК папилломавирусов человека (ВПЧ) в бытовых стоках

Human papillomavirus (HPV) appears to be significant danger for mankind because of having very high widespread and might revealing the pandemy of papillomatoses. To the present time, about 200 types of HPV have been found, 40 types from which announced as high-risk cancerogenic. It was learned that papillomaviruses are very resistant to impacts of environmetal factors because they posseses many possibilities for long surviving in polluted water conditions. Nevertheless, the infection of HPV through the contact with contaminated water areas still does not to be prove with strong scientific data, foreign scientists are seriously bothering about facts of finding of DNA of human papillomaviruses in sewage water and in different deteriorated water objects. Our opinion is based on the necessity of the comprehensive investigation of the presence of the high-risk oncogenic types of HPV in sewage water. The present study is devoted for the first time to the data of finding of DNA of several high-risk oncogenic HPV in sewage water. Three pairs of primers were used in the study, between them 2 pairs of universal primers (GP5+/6+) which were very specific to nucleic sequences encoded the main structural element of the HPV capsid, the “late” protein L1 (HPV6 L1, HPV11 L1 and HPV16 L1). As the result, the presence of DNA of high-risk oncogenic papillomaviruses of types 6 and 16 was shown in sewage water. Further, the scope of investigations directed to finding of the presence of HPV components is planned to be arranged not only for sewage water but for other water areas of Irkutsk Region of East Siberia as well around water areas of the Lake Baikal.

Reliability of conventional Papanicolaou smear in diagnosing bacterial vaginosis among women with clinical genital infection.

Objective:Bacterial vaginosis (BV) is a common reproductive tract infection (RTI) reported among Indian women. BV can influence the persistence of high-risk oncogenic human papillomavirus, a causative factor for cervical cancer. BV and cervical cancer are major public health issues in a developing country like India. It becomes important for a resource-constrained country like India with poor healthcare access to implement control measures to screen and treat RTI in an attempt to prevent the risk for cervical cancer. Papanicolaou (Pap) smear is an established screening tool for cervical cancer and the diagnosis of RTIs, forms a part of its evaluation. The present study explores the validity of conventional Pap smear in diagnosing BV.Methodology:Pap smear and Gram stain smear were collected for 254 women with clinically evident cervicitis/cervicovaginitis (genital infection). Using the Nugent score on Gram stain as a gold standard, we determined the sensitivity and specificity of Pap smear to diagnose BV.Results:The overall prevalence of BV in the study population was 44% using the Nugent score. Pap smear showed sensitivity and specificity of 70.9%. (CI- 61.5% - 79.2%) and 56.8% (CI – 48.2%–65.2%), respectively. The positive predictive value of Pap smear to diagnose BV was 56.5% (CI – 47.8%–64.9%), and the negative predictive value was 71.2% (CI – 61.8%–79.4%).Conclusion:In the present study, conventional Pap smear demonstrates good accuracy to detect BV. Pap testing for cervical cancer screening can additionally serve as an effective screening tool for diagnosing BV among women with genital infection in healthcare settings.

Synthesis and Evaluation of Anisomelic acid-like Compounds for the Treatment of HPV-Mediated Carcinomas

The vast majority of cervical and 75% of oropharyngeal carcinomas are triggered by infection with a type of high-risk oncogenic human papillomavirus (HPV). It is well-known that E6 and E7 oncoproteins are critical for viral-induced cancer, and hence, they represent valuable targets for therapeutic intervention in HPV-mediated cancers. Our earlier research on the cembranoid, anisomelic acid (AA) showed that, AA has the potential to induce apoptosis in HPV cells by the depletion of E6 and E7 oncoproteins. The present study describes the structure-activity relationship and the evaluation of synthetic AA like compounds, i.e simplified cembranoid-like structures, as HPV inhibitors against some papilloma cell lines. Both from experimental and computational results, we observed that these compounds induced apoptosis by the same E6/E7-based mechanism as AA, but at earlier time points, thus being far more effective than AA. Further, the data indicated that only part of the structure of AA is required for the molecular action. Based on these results, we identified some novel and potential compounds for specific treatment of HPV-associated carcinomas.

Assessing survival rate of HPV-positive and HPV-negative cervical cancer patients

Currently, studies highlighting features of emergence, development, clinical score and prognosis for patients with HPV-negative cervical cancer are scarce. However, the data regarding high recurrence rate and mortality in patients with HPV-negative head and neck cancer are demonstrated. Here, cervical canal and exocervical scraping samples collected from 116 patients with primary cervical cancer, I–IV stages, aged 24 to 79 years, were examined with real-time PCR assay for assessing prevalence of 12 high oncogenic risk human papillomavirus (HPV) strains, genotyping and viral load. It was found that 84 (72.4%) and 32 cervical cancer patients (27.6%) were positive and negative, respectively, for high oncogenic risk (HR) HPV strains. Based on these data, patients were further subdivided into two groups: HPV-positive and HPVnegative patient group. Genotyping HPV-positive samples revealed that HPV genotype 16 was found in 67.8% of cases that agrees with data published worldwide. In addition, relapse-free and overall survival (HPV-positive and HPV-negative patients) rate were also evaluated in both groups. It was demonstrated that survival rate was significantly decreased in HPVnegative cervical cancer patients additionally characterized by less favorable prognosis. Moreover, length of relapse-free survival as well as overall survival for HPV-positive vs. HPV-negative patients was 102 vs. 68 months as well as 52 vs. 83 months, respectively. On the other hand, it was demonstrated that recurrence rate, clinical score and progression of cervical cancer directly depend on cancer spread observed at primary medical examination. Of note, the majority of primary cervical cancer relapses are diagnosed within the first 2 years after completing treatment. In addition, an increasing relapse rate has been documented in cervical cancer patients at advanced stages. Upon that, biological cancer behavior remains poorly predictable even in patients at similar disease stage. Therefore, it is essential that HPV as an important prognostic factor would be taken into account for choosing proper therapeutic strategy for treatment of patients with cervical cancer.

Characterization of High-risk Oncogenic Human Papillomavirus Genotypes in Histologically Confirmed Ear, Nose and Throat (Ent) Cancers in Burkina Faso.

Background:High-risk human papillomavirus (HPV-HR) infections are responsible for 99.99% of cervico-uterine cancers and 50% of carcinomas of the oropharynx. Objective:To characterize high-risk HPV genotypes (HPV-HR) in histologically confirmed ear, nose and throat (ENT) cancers in Ouagadougou. Methods:One hundred and twenty-eight archived tissues from the ENT sphere, obtained over the last ten years (2007 to 2017) and histologically diagnosed in anatomy and pathology-cytology laboratories in Ouagadougou were included. These tissues were dewaxed with xylene; HPV DNA extraction was performed and HPV-HR were researched by real-time multiplex PCR. Results:Among the fourteen HPV-HR genotypes tested for, seven were identified. The prevalence of HPV-HR infection was 15.6%. The most common genotypes were: HPV56 (45%) and HPV33 (20%). Squamous cell carcinomas accounted for 75% of cases, followed by lymphomas for 10%. The age range was between 5 and 80 years. Conclusion:The results show the involvement of a diversity of HPV-HR genotypes and a high frequency of HPV56 and HPV33 in ENT cancers in Ouagadougou, Burkina Faso. The appropriate HPV vaccination will considerably reduce the number of these cancers.

A clinicopathological and molecular analysis of cervical carcinomas with basaloid features.

To investigate the relationship between adenoid basal carcinoma (ABC), adenoid cystic carcinoma (ACC) and squamous cell carcinoma (SCC) in the uterine cervix. We analysed the clinicopathological and molecular features in two pure ABCs, 15 SCCs with ABC-/ACC-like features and seven basaloid SCCs (BSCCs) by chart review, immunohistochemistry, human papillomavirus (HPV) RNA in-situ hybridisation and fluorescence in-situ hybridisation. All patients were alive with no evidence of disease, except for one patient with ACC-like features who died of disease at 18months post diagnosis. The mixed carcinomas comprised variable SCCs and ABC-/ACC-like components displaying vague transitional zones. All components consistently showed diffuse p16, p63 and SOX2, variable cytokeratin (CK)7 and CK17 and rare Ber-EP4 and MYB expression; there was a substantially lower Ki67 index in pure ABCs and the ABC-like components. The ACC-like components showed no myoepithelial differentiation (SMA, calponin and S100) and MYB gene fusions. CK7, CK17 and Ber-EP4 were characteristically stronger in BSCCs than in the mixed carcinomas (P<0.01). High-risk HPV (HR-HPV) E6/E7 mRNA was detected in 12 mixed carcinomas and seven BSCCs, but not in pure ABCs. The HR-HPV mRNA expression was higher in the SCC components and BSCCs than in the ABC-like components of mixed carcinomas (P<0.05). The ACC-like components in mixed carcinomas probably represent the morphological mimics of salivary ACCs. ABC-like components may be the potential precursor of the ACC-like and SCC components. HR-HPV oncogenes may play a role in the pathogenesis of SCCs with ABC-/ACC-like features.

The antiproliferative action of the “early” protein of papillomavirus HPV16 E2 on testis toumors of mice induced by the injection of Hela cells

The аntiploliferative effect of the “early” protein of high-risk oncogenic human papillomavirus HPV16 E2 on mice testis tumors was discovered after the indyction that was happened after the intramuscular injection of cancer HeLa cells suspension. The regression of mice testis tumors was mostly dramatic during first 1-2 days after oral vaccination with HPV16 E2 (500 mg per mice) made in tomato plant expression system that was gradually decreasing to control variant. The typical monolayer of HeLa cells on the cultivation flask bottom was appeared after seeding of testis tissue cells on the DMEM medium they were only for 18% functionally active according to the detection by the staining with nitroblue tetrazolium and trypane blue.

The Antiproliferative Effect of the "Early" Protein E2 of Papillomavirus HPV16 on Testis Tumors of Mice Induced by the Injection of HeLa Cells.

The antiproliferative effect of the "early" protein E2 of the high-risk oncogenic human papillomavirus HPV16 on mouse testis tumors, which were induced by the intramuscular injection of HeLa cells, was discovered. The regression of tumors was maximum in the first 2 days after the oral vaccination with HPV16 E2 (500 mg per mouse) and then gradually decreased to the control variant. A typical monolayer of HeLa cells on the cultivation flask bottom, of which only 18% were functionally active, appeared after seeding testis tissue cells on DMEM medium.

Transcriptome sequencing profiles of cervical cancer tissues and SiHa cells

High-risk human papillomavirus (HPV) is a causal factor for cervical cancer, of which HPV16 is the predominant genotype, but the detailed mechanism remains to be elucidated. In this study, we performed transcriptome sequencing in cervical cancer tissues with HPV16-positive and normal tissues with HPV16-negative, and SiHa cells with or without HPV16 E6/E7 knockdown, and identified 140 differential expressed genes (DEGs) in two data sets. We carried out a series of bioinformatic analyses to learn more about the 140 DEGs, and found that 140 DEGs were mostly enriched in cell cycle and DNA repair through Kyoto Encyclopedia of Genes and Genomes pathway enrichment, Gene Ontology annotation, and gene set enrichment analysis. A total of 20 genes including RMI1, MKI67, FANCB, KIF14, CENPI, RACGAP1, EXO1, KIF4A, FOXM1, C19orf57, PSRC1, NUSAP1, CIT, NDC80, MCM7, GINS2, MCM6, ORC1, TLX2, and UHRF1 were screened by co-expression analysis; of those, the expressions of 6 (CENPI, FANCB, KIF14, ORC1, RACGAP1, and RMI1) were verified by qRT-PCR. Further, we found that E2F family, NF-Y, AhR:Arnt, and KROX family may be involved in modulating DEGs by TransFind prediction. TF2DNA database and co-expression analysis suggested that 12 TFs (ZNF367, TLX2, DEPDC1B, E2F8, ZNF541, EGR2, ZMAT3, HES6, CEBPA, MYBL2, FOXM1, and RAD51) were upstream modulators of DEGs. Our findings may provide a new understanding for effects of HPV oncogenes in the maintenance of cancerous state at the transcriptional level.

Abstract LB-200: A cGMP-grade chimeric papillomavirus candidate vaccine (HPV16 RG1-VLP) confers long term cross-protection compared to a nonavalent hpv vaccine in a pre-clinical papillomavirus animal model

Abstract Background: The National Cancer Institute (NCI) PREVENT Cancer Program (PREVENT) is a peer-reviewed R&amp;D pipeline with the core emphasis on preclinical development and clinical translation of novel cancer preventive interventions. One of the latest PREVENT-supported projects include cGMP production and IND enabling studies of a broad spectrum experimental human papillomavirus (HPV) vaccine- HPV16 RG1-VLP. This monovalent chimeric virus-like particle (VLP) displays 360 copies of the highly conserved epitope RG1 (aa 17-36 of minor capsid protein HPV16 L2) in the DE loop of HPV16L1 VLP backbone, and is capable of eliciting broadly neutralizing antibodies that target several clinically relevant HPV genotypes. RG-1 induced cross-neutralizing titers are typically lower than anti-L1 antibodies generated by currently licensed HPV vaccines. Hence, durability of protection has been cited as a cause of concern. Here, using engineering-run cGMP grade HPV16-RG1VLPs formulated with alhdyrogel®, the durability of protection 6 month post-vaccination of HPV16 RG1-VLPs against Gardasil-9®, a licensed HPV vaccine was evaluated using an established papillomavirus disease model. Methods: New Zealand white rabbits (n=15 per treatment group) were administered three intra-muscular vaccinations of HPV16-RG1 (80 µg), human doses of Gardasil-9®, or no vaccine (adjuvant only). Following vaccination, in vivo protection was assessed against 8 high-risk oncogenic HPVs utilizing methods from an established cottontail rabbit papillomavirus (CRPV) disease model. Within each treatment group, 5 rabbits were challenged two weeks post-final vaccination (at peak serum ELISA titer), while another 5 were challenged six months post-final vaccination to assess durability of protection. The remainder 5 rabbits will be challenged one year post final vaccination. Results: During the peak-titer period, rabbits vaccinated with monovalent HPV16-RG1VLP were protected from disease development, which was comparable to the protection afforded by Gardasil-9®. Six months after final vaccination, despite lower serum titers, HPV16-RG1VLP immunized rabbits were still protected from disease development with vaccine efficacy comparable to that of Gardasil-9®. And, in some instances, HPV16-RG1VLP vaccine demonstrated a superior cross-protection. Conclusions: Even as a monovalent formulation, HPV16 RG1 VLP vaccination was able to provide comparable protection against a number of high-risk oncogenic HPV types, including types not covered by Gardasil-9®, even after six months post-vaccination. As a monovalent VLP, HPV16 RG1 VLP holds promise as a broad-spectrum preventative vaccine candidate that could potentially provide broader protection at lower production costs. Studies evaluating protection one-year-post vaccination is currently in progress. Citation Format: Jiafen Hu, Karla Balogh, Ken Matsui, Huimin Tan, Pola Olczak, George Buchman, Brian Howard, Jonathan White, Michelle Kennedy, Shizuko Sei, Elizabeth Glaze, Sarah Brendle, Christina Schellenbacher, Reinhard Kirnbauer, Richard Roden, Robert Shoemaker, Neil Christensen, Joshua Weiyuan Wang. A cGMP-grade chimeric papillomavirus candidate vaccine (HPV16 RG1-VLP) confers long term cross-protection compared to a nonavalent hpv vaccine in a pre-clinical papillomavirus animal model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-200.