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Objective: We aimed to investigate differences between HPV‐16 mono‐ and HPV‐16/18 co‐infections in terms of cervical dysplasia and invasive cancer. Methods: This multicentre, retrospective study spanned from December 2017 to December 2020, involving women who visited gynaecological oncology clinics for colposcopy with either HPV‐16 or HPV‐16/18 positivity. A total of 736 patients, 670 in Group 1 (HPV‐16 positivity) and 66 in Group 2 (HPV‐16/18 positivity), were compared for the presence of CIN2+ lesions detected by colposcopic biopsy or endocervical curettage (ECC). Exclusions included hysterectomized patients, those with prior gynaecological cancers, and patients with HPV positivity other than types 16 and 18. Results: Among the included patients, 42.4% had a diagnosis of CIN2+ lesions. The cytology results demonstrated abnormal findings in 45.3% in Group 1 and 42.2% in Group 2, with no significant difference between the groups. ECC revealed CIN2+ lesion in 49 (8.7%) patients in group 1, while only 1 (1.7%) patient had CIN2+ lesion in group 2. There was no difference between 2 groups in terms of ECC result (p = 0.052). In group 1, 289 (43.1%) patients had CIN2+ lesion, while 23 (34.8%) patients had CIN2+ lesions in group 2. There was no difference between group 1 and 2 in terms of diagnosis of CIN2+ lesions (p = 0.19). Conclusion: This multicentre retrospective study found no significant differences between HPV‐16 mono‐ and HPV‐16/18 co‐infections regarding cervical pathologies. Larger studies are needed to validate and further explore these findings. [ABSTRACT FROM AUTHOR]

Background: Oesophageal malignancies (OC) are the sixth most common cause of cancer-related mortality worldwide. Traditional risk factors for OC include smoking, alcohol consumption, and poorly controlled acid reflux; however, the trends in the last decade have pointed out the potential carcinogenic roles of infectious agents, especially Human Papillomavirus (HPV), in the development of OC. The prevalence of HPV infection in OC varies greatly worldwide, mainly due to the inconsistencies of the detection assays employed. This study attempted to establish the association between high-risk HPV and oesophageal malignancies by detecting the transcriptionally active HPV mRNA. Materials and Methods: In this cross-sectional study, 30 malignant oesophageal samples were subjected to real-time PCR to detect high-risk HPV-16 and 18 by targeting transcriptionally active E6/E7 genes. The positive samples were further subjected to viral load assessment. Results: Histopathological analysis of the patients showed that a moderately differentiated squamous cell carcinoma was seen in 56.2% of the cases. Of the 30 samples, 4 (13.3%) showed positive for HPV-16 E6/E7, and none showed positive for HPV-18 E6/E7. The viral load of HPV-16 E6/E7 in the positive samples was lesser than the copies present in the well-established cell line, SiHa. Conclusion: The role of HPV in the etiopathogenesis of oesophageal malignancies is unclear. Based on this study and the supporting data presented, it can be said that the association of high-risk HPV infection in oesophageal cancers does exist, but whether it is clinically and etiologically significant is the question that needs to be answered. Multicenter studies from different geographical locations, employing multiple molecular methods with a larger sample size, could aid in a better understanding of the etiopathogenesis of HPV in OC. [ABSTRACT FROM AUTHOR]

Cervical cancer remains a significant cause of morbidity and mortality in women worldwide and is the leading cause of cancer-related death in Botswana. It is well established that women with HIV have a higher risk of persistent HPV infection leading to cervical cancer. We assessed HPV prevalence and genotype distribution in 126 tissue specimens from confirmed invasive cervical cancer cases using Abbott real-time PCR assay. Overall, 88 (69.8%) women were HIV-infected. Fifty-seven (64.8%) of the HIV-infected women had a baseline CD4+ count ≥350 cells/μl, and 82 (93.2%) were on antiretroviral therapy at the time of cervical cancer diagnosis. The median age of HIV-infected patients was significantly younger than that of HIV-uninfected patients (p

Background and Objectives: Even if they are cells of controversial origin (mesenchymal, perivascular, or fibroblastic), follicular dendritic cells (FDC) are present in all organs. The aim of this study was to establish the FDC expression pattern and its interrelation with HPV 18 expression in laryngeal squamous cell carcinoma (LSCC). Materials and Methods: Fifty-six cases of LSCC were evaluated by simple and double immunostaining. The following score was used: 0 (negative or few positive cells), 1 (10–30% of positive cells), 2 (30–50% of cells), and 3 (over 50% of cells). Results: The expression of CD 21-positive cells with dendritic morphology (CDM) was noticed in the intratumoral area of conventional (well and poorly differentiated types and HPV 18 positive cases with a value of 2 for the score) and papillary types (HPV-18 negative cases with a score of 1). The highest value of 2 for the score of CDM in HPV-18 positive cases was found in the peritumoral area of well- and poorly-differentiated conventional LSCCs. A significant correlation was found between scores of CDM from the intratumoral area and those of the peritumoral area (p = 0.001), between CDM and non-dendritic morphology cells (NDM) of the intratumoral area (p = 0.001), and between HPV-18 status and peritumoral NDM cells (p = 0.044). Conclusions: The FDC and NDM cell score values of intratumoral and peritumoral areas may represent important parameters of LSCCs. This may contribute to a better stratification of laryngeal carcinoma cases and the individualized selection of clinical treatment protocols. [ABSTRACT FROM AUTHOR]

Persistent infection with human papillomavirus (HPV) significantly contributes to the development of cervical cancer. Thus, it is urgent to develop rapid and accurate methods for HPV detection. Herein, we present an ultrasensitive CRISPR/Cas12a-based electrochemiluminescent (ECL) imaging technique for the detection of HPV-18 DNA. The ECL DNA sensor array is constructed by applying black hole quencher (BHQ) and polymer dots (Pdots) co-labeled hairpin DNA (hpDNA) onto a gold-coated indium tin oxide slide (Au-ITO). The ECL imaging method involves an incubation process of target HPV-18 with a mixture of crRNA and Cas12a to activate Cas12a, followed by an incubation of the active Cas12a with the ECL sensor. This interaction causes the indiscriminate cleavage of BHQ from Pdots by digesting hpDNA on the sensor surface, leading to the restoration of the ECL signal of Pdots. The ECL brightness readout demonstrates superior performance of the ECL imaging technique, with a linear detection range of 10 fM–500 pM and a limit-of-detection (LOD) of 5.3 fM. The Cas12a-based ECL imaging approach offers high sensitivity and a broad detection range, making it highly promising for nucleic acid detection applications. [Display omitted] • A target activated Cas12a ECL imaging biosensing platform was constructed for quantitative nucleic acid detection. • The ECL imaging method demonstrated rapid, sensitive, and specific detection of HPV-18 DNA. • The proposed method can be conveniently used for ECL detection of multiple targets. • This work advanced the use of ECL imaging in biomedical research. [ABSTRACT FROM AUTHOR]

OBJETIVOS. Las propiedades mecánicas de las células sufren cambios profundos durante el proceso de tumorigénesis, y son determinantes para comportamientos tumorales tales como la invasión y la metástasis. Nuestro objetivo es estudiar los cambios mecánicos que ocurren en etapas intermedias de este proceso, así como los cambios de morfología celular que frecuentemente acompañan a las alteraciones en el fenotipo mecánico. Para ello, utilizamos queratinocitos humanos (línea celular HaCaT, usada frecuentemente en estudios de biología oral) que expresan los oncogenes del HPV -18, y que constituyen entonces un modelo de etapa intermedia en el proceso de tumorigénesis oral. MÉTODOS. Utilizamos microscopía de fuerza atómica en el modo de nanoindentación y en el modo de mapeo nanomecánico cuantitativo para obtener medidas del módulo de Young y mapas mecánicos de la superficie celular, respectivamente. Además, utilizamos microscopía confocal para obtener parámetros morfológicos celulares. RESULTADOS. Observamos una disminución significativa en el módulo de Young en células HaCaT que expresan los oncogenes del HPV-18, y una disminución de la rigidez en las zonas de contacto célula célula. Por otra parte, la morfología celular se vuelve significativamente más redondeada en las células HaCaT que expresan los oncogenes del HPV-18. CONCLUSIONES. Nuestros resultados apoyan la hipótesis de que la disminución en la rigidez celular es un cambio mecánico que ocurre en etapas tempranas de la tumorigénesis oral, y que puede estar acompañado de cambios en la morfología celular

Background and Objectives: Even if they are cells of controversial origin (mesenchymal, perivascular, or fibroblastic), follicular dendritic cells (FDC) are present in all organs. The aim of this study was to establish the FDC expression pattern and its interrelation with HPV 18 expression in laryngeal squamous cell carcinoma (LSCC). Materials and Methods: Fifty-six cases of LSCC were evaluated by simple and double immunostaining. The following score was used: 0 (negative or few positive cells), 1 (10–30% of positive cells), 2 (30–50% of cells), and 3 (over 50% of cells). Results: The expression of CD 21-positive cells with dendritic morphology (CDM) was noticed in the intratumoral area of conventional (well and poorly differentiated types and HPV 18 positive cases with a value of 2 for the score) and papillary types (HPV-18 negative cases with a score of 1). The highest value of 2 for the score of CDM in HPV-18 positive cases was found in the peritumoral area of well- and poorly-differentiated conventional LSCCs. A significant correlation was found between scores of CDM from the intratumoral area and those of the peritumoral area (p = 0.001), between CDM and non-dendritic morphology cells (NDM) of the intratumoral area (p = 0.001), and between HPV-18 status and peritumoral NDM cells (p = 0.044). Conclusions: The FDC and NDM cell score values of intratumoral and peritumoral areas may represent important parameters of LSCCs. This may contribute to a better stratification of laryngeal carcinoma cases and the individualized selection of clinical treatment protocols.

Abstract Background In several years ago, infection with human papillomaviruses (HPVs), have been prevalent in the worlds especially HPV type 18, can lead to cervical cancer. Therefore, rapid, accurate, and early diagnosis of HPV for successful treatment is essential. The present study describes the development of a selective and sensitive electrochemical biosensor base on DNA, for early detection of HPV-18. For this purpose, a nanocomposite of reduced graphene oxide (rGO) and multiwalled carbon nanotubes (MWCNTs) were electrodeposited on a screen-printed carbon electrode (SPCE). Then, Au nanoparticles (AuNPs) were dropped on a modified SPCE. Subsequently, single strand DNA (ssDNA) probe was immobilized on the modified electrode. The link attached between AuNPs and probe ssDNA provided by l-cysteine via functionalizing AuNPs (Cys-AuNPs). The differential pulse voltammetry (DPV) assay was also used to electrochemical measurement. The measurement was based on the oxidation signals of anthraquninone-2-sulfonic acid monohydrate sodium salt (AQMS) before and after hybridization between the probe and target DNA. Results The calibration curve showed a linear range between 0.01 fM to 0.01 nM with a limit of detection 0.05 fM. The results showed that the optimum concentration for DNA probe was 5 µM. The good performance of the proposed biosensor was achieved through hybridization of DNA probe-modified SPCE with extracted DNA from clinical samples. Conclusions According to the investigated results, this biosensor can be introduced as a proprietary, accurate, sensitive, and rapid diagnostic method of HPV 18 in the polymerase chain reaction (PCR) of real samples.

Carcinoma precursor lesion caused by persistent infection of human papillomavirus (HPV) types 16 and 18 is known as a principal inducer of cervical cancer. Therefore, rapid and effective detection of HPV‐16 and HPV‐18 infection at early stage is an important strategy for preventing such disease. In this study, a novel duplex nanoparticle‐assisted polymerase chain reaction (nanoPCR) assay was developed to detect both of the two genotypes simultaneously. Two pairs of primers for nanoPCR were designed based on the conserved region within the early 6 (E6) gene of HPV‐16 and HPV‐18, respectively. After optimizing reaction conditions, the nanoPCR assay displayed 10‐fold more sensitive than that of conventional PCR and showed high specificity. The detection limit of nanoPCR was 1.7 × 101 copies/μL for HPV‐16, 1.2 × 102 copies/μL for HPV‐18, and no cross‐reaction was detected after using other viruses or HPV subtypes as templates. Of 209 clinical samples collected from patients, as also confirmed by sequencing, the nanoPCR method gave consistent results with conventional PCR assay: 7 positives for HPV‐16, 4 positives for HPV‐18, and no co‐infection. Here is the first report to introduce a reproducible nanoPCR assay for detecting HPV DNA with high sensitivity and specificity, which may point out a useful diagnostic tool for potential clinical application. Highlights: A novel nanoPCR method was developed for the detection of HPV‐16 and HPV‐18.The HPV nanoPCR assay was 10‐fold more sensitive than conventional PCR assay.The lower detection limit was 1.7 × 101 copies/μL for HPV‐16 and 1.2 × 102 copies/μL for HPV‐18. [ABSTRACT FROM AUTHOR]

Background: In several years ago, infection with human papillomaviruses (HPVs), have been prevalent in the worlds especially HPV type 18, can lead to cervical cancer. Therefore, rapid, accurate, and early diagnosis of HPV for successful treatment is essential. The present study describes the development of a selective and sensitive electrochemical biosensor base on DNA, for early detection of HPV-18. For this purpose, a nanocomposite of reduced graphene oxide (rGO) and multiwalled carbon nanotubes (MWCNTs) were electrodeposited on a screen-printed carbon electrode (SPCE). Then, Au nanoparticles (AuNPs) were dropped on a modified SPCE. Subsequently, single strand DNA (ssDNA) probe was immobilized on the modified electrode. The link attached between AuNPs and probe ssDNA provided by l-cysteine via functionalizing AuNPs (Cys-AuNPs). The differential pulse voltammetry (DPV) assay was also used to electrochemical measurement. The measurement was based on the oxidation signals of anthraquninone-2-sulfonic acid monohydrate sodium salt (AQMS) before and after hybridization between the probe and target DNA. Results: The calibration curve showed a linear range between 0.01 fM to 0.01 nM with a limit of detection 0.05 fM. The results showed that the optimum concentration for DNA probe was 5 µM. The good performance of the proposed biosensor was achieved through hybridization of DNA probe-modified SPCE with extracted DNA from clinical samples. Conclusions: According to the investigated results, this biosensor can be introduced as a proprietary, accurate, sensitive, and rapid diagnostic method of HPV 18 in the polymerase chain reaction (PCR) of real samples. [ABSTRACT FROM AUTHOR]

It is suggested that HPV-18 variants from the A lineage have higher oncogenic potential compared to B variants. Some studies show uneven distribution of HPV-18 variants in cervical adenocarcinomas and squamous cell carcinomas. Regarding HPV-18 variants’ functions, the few studies reported focus on E6, and none were performed using natural host cells. Here, we immortalized primary human keratinocytes (PHKs) with E6/E7 of HPV-18 A1 and B1 sublineages and functionally characterized these cells. PHK18A1 reached immortalization significantly faster than PHK18B1 and formed a higher number of colonies in monolayer and 3D cultures. Moreover, PHK18A1 showed greater invasion ability and higher resistance to apoptosis induced by actinomycin-D. Nevertheless, no differences were observed regarding morphology, proliferation after immortalization, migration, or epithelial development in raft cultures. Noteworthy, our study highlights qualitative differences among HPV-18 A1 and B1 immortalized PHKs: in contrast to PHK18A1, which formed more compact colonies and spheroids of firmly grouped cells and tended to invade and migrate as clustered cells, morphologically, PHK18B1 colonies and spheroids were looser, and migration and invasion of single cells were observed. Although these observations may be relevant for the association of these variants with cervical cancer of different histological subtypes, further studies are warranted to elucidate the mechanisms behind these findings.

Background: Despite being preventable, cervical cancer remains a major health concern among women. Persistent Human Papillomavirus (HPV) and other viral co-infections may influence cervical dysplasia. We determined and compared the prevalence and risk factors of cervical viral infections among the tribal and general population of southern coastal Karnataka, India. Methods: A population-based cross-sectional survey was conducted among 1140 and 1100 women from tribal and general population, respectively. Cervical infections with HPV, Epstein-Barr Virus (EBV), Cytomegalovirus (CMV) and Herpes-Simplex Virus (HSV) were examined using polymerase chain reactions (PCR) and DNA sequencing. Results: HPV prevalence was higher among tribal women (40.6%) than general population (14.3%) while the prevalence of EBV (55.1%) and CMV (49.4%) were lower among tribal women than general population (74.3% and 77.5%, respectively). HSV infection was observed in tribal women only (1.8%). Among HR-HPV strains, HPV-18 was predominant among tribal population (28.3%) while, HPV-16 was predominant among the general population (9.1%). Infections were associated with age, educational status, unemployment and personal hygiene of tribal women. Phylogenetic analysis revealed that HPV-16 variants of tribal participants were closely related to non-European sublineages indicating greater risk of HPV persistence and carcinogenesis. Conclusion: The study provides a comparative estimate for DNA virus infections of the cervix among women from general as well as tribal population in this region and also reveals a different type-specific pattern of viral infection. Further research is required to delineate the role of specific interactions between multiple virus infections and their role in carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: Human papillomaviruses are the most important causative agents for invasive cervical cancer development. HPV type-specific vaccination and HPV cervical cancer screening methods are being widely recommended to control the disease but the epidemiology of the circulating HPV types may vary locally. The circulating HPV-strains have never been assessed in Burundi. This study determined the prevalence and genotype-specific distribution of HPV in four different strata in Burundi: HIV-infected or non-infected and women living in rural or urban areas. Implications for HPV diagnosis and vaccine implementation was discussed. Methods: Four cross-sectional surveys were conducted in Burundi (2013 in a rural area and 2016 in urban area) among HIV-infected and uninfected women living in rural and urban areas. Liquid-Based Cytology (LBC) and HPV genotyping were performed and risk factors for HPV infection and cervical pre-cancer lesions were determined using logistic regression model. Results: HPV prevalence was very high in urban area with significant differences between HIV-positive and negative women (p<0.0001). In fact, 45.7% of HIV-positive participants were infected with any HPV type and all were infected with at least one HR/pHR-HPV type. Among the HIV-negative participants, 13.4% were HPV-infected, of whom, only four women (2.7%) were infected with HR/pHR-HPV types. In rural area, HPV infection did not significantly differ between HIV-positive and negative women (30.0% and 31.3% respectively; p = 0.80). In urban area, multiple infections with HR/pHR-HPV types were detected in 13.9% and 2.7% among HIV-positive and negative women respectively (p<0.0001), whereas in rural area, multiple infections with HR/pHR-HPV types were detected in 4.7% and 3.3% of HIV-positive and negative women respectively (p = 0.56). The most prevalent HR/pHR-HPV types in HIV-positive women living in urban area were HPV 52, 51, 56, 18 and 16 types. In HIV-negative women living in urban area, the most prevalent HR/pHR-HPV types were HPV 66, 67, 18, 45 and 39 types. In HIV-positive women living in rural area, the most prevalent HR/pHR-HPV types were HPV 66, 16, 18 and 33 types. In HIV-negative women living in rural area, the most prevalent HR/pHR-HPV types were HPV 16, 66, 18, 35 and 45 types. Independent risk factors associated with cervical lesions were HPV and HIV infections. Conclusions: There is a high burden of HR and pHR-HPV infections, in particular among HIV-infected women living in urban area. The study points out the need to introduce a comprehensive cervical cancer control programme adapted to the context. This study shows that the nonavalent vaccine covers most of the HR/pHR-HPV infections in rural and urban areas among HIV-infected and uninfected women. [ABSTRACT FROM AUTHOR]

The Human Papillomavirus E7 oncoprotein plays an essential role in the development and maintenance of malignancy, which it achieves through targeting a number of critical cell control pathways. An important element in the ability of E7 to contribute towards cell transformation is the presence of a Casein Kinase II phospho-acceptor site within the CR2 domain of the protein. Phosphorylation is believed to enhance E7 interaction with a number of different cellular target proteins, and thereby increase the ability of E7 to enhance cell proliferation and induce malignancy. However, there is little information on how important this site in E7 is, once the tumour cells have become fully transformed. In this study, we have performed genome editing of the HPV-18 E7 CKII recognition site in C4-1 cervical tumour-derived cells. We first show that mutation of HPV18 E7 S32/S34 to A32/A34 abolishes CKII phosphorylation of E7, and subsequently we have isolated C4-1 clones containing these mutations in E7. The cells continue to proliferate, but are somewhat more slow-growing than wild type cells, reach lower saturation densities, and are also more susceptible to low nutrient conditions. These cells are severely defective in matrigel invasion assays, partly due to downregulation of matrix metalloproteases (MMPs). Mechanistically, we find that phosphorylation of E7 plays a direct role in the ability of E7 to activate AKT signaling, which in turn is required for optimal levels of MMP secretion. These results demonstrate that the E7 CKII phospho-acceptor site thus continues to play an important role for E7’s activity in cells derived from cervical cancers, and suggests that blocking this activity of E7 could be expected to have therapeutic potential. [ABSTRACT FROM AUTHOR]

Background: High-risk human papillomavirus (HR-HPV) has been demonstrated to be the necessary cause of cervical carcinoma. High-risk HPV detection has a prognostic significance for the women who are at increased risk of disease progression. HPV genotyping in cervical cancer precursor lesions is crucial for prevention and management of cervical cancer. This study was designed to investigate the distribution of HR-HPV genotypes among a group of patients with high-grade squamous intraepithelial lesions and higher, of the cervix, in Botswana. Materials and methods: 185-archived residual formalin-fixed paraffin-embedded cervical biopsies collected between the years, 2006 and 2008 were studied. These tissues were diagnosed with HSIL (n = 146) and squamous cell carcinoma (n = 39). DNA was extracted using the Abbott m2000 analyser (Abbott Laboratories, Illinois) using reagents provided by the manufacturer. HPV genotyping was done using the Abbott RealTime HR-HPV PCR, which qualitatively detects 14 HR-HPV (reported as HPV 16, 18 & Other HR-HPV). Results: DNA was successfully extracted from 162/185 (87.6%) tissues as indicated by a positive β-globin test. 132/162 (82%) tested positive for HR-HPV The HPV 16 prevalence was 50% (66/132), HPV 18 at 15.2% (20/132) and other Group 1 HR-HPV plus HPV 66 and 68 had a prevalence of 56.1% (74/132). Other HR-HPV types were common in HSIL than in carcinoma, while HPV 16 was more prevalent in carcinomas than other HR-HPV genotypes. Conclusion: In this study, HPV 16 and other HR-HPV genotypes were commonly associated with HSIL but HPV 18 was uncommon among Botswana women. Our data highlights the need for multivalent HPV vaccines with cross coverage for other high risk HPV other than HPV 16 and 18. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) vaccination and the implementation of primary HPV screening in the Netherlands will lead to a lower cervical disease burden. For evaluation and further improvement of prevention, it is important to estimate the magnitude and timing of health benefits of current and alternative vaccination strategies such as vaccination of boys or adults. Methods and findings: We evaluated the impact of the current girls-only vaccination program and alternative strategies on cervical disease burden among the first four vaccinated five-year birth cohorts, given the context of primary HPV screening. We integrated the existing microsimulation models STDSIM (HPV transmission model) and MISCAN-Cervix (cervical cancer screening model). Alternative vaccination strategies include: improved vaccination uptake, including routine boys vaccination, and offering adult vaccination at sexual health clinics. Our models show that the current vaccination program is estimated to reduce cervical cancers and cancer deaths by about 35% compared to primary HPV screening in the absence of vaccination. The number needed to vaccinate (NNV) to gain 1 life year is 45. The most efficient alternative vaccination strategies are: 1) improving coverage of girls to 80% (NNV = 42); and 2) routine vaccination for girls and boys at 80% coverage (incremental NNV = 155), with cervical cancer mortality reductions estimated at 50% and 60% respectively. Conclusions: While the current program already substantially reduces cervical cancer incidence and mortality, prevention can be further improved by increasing vaccination uptake and extending vaccination to boys. As not all cervical cancer deaths will be prevented, screening participation should still be encouraged. [ABSTRACT FROM AUTHOR]

Bivalent human papillomavirus (HPV) vaccine was incorporated into the childhood vaccination calendar in Galicia, Spain in 2008. The objectives of this study were to estimate direct, indirect and total effectiveness of HPV vaccine and to identify sexual habits changes in the post-vaccination period in Galicia, Spain.Endocervical scrapings of 745 women attending 7 Health Areas of the Galician Public Health Service were collected in the post-vaccination period, from 2014–2017. Two groups were studied: women born between 1989 and 1993 (n = 397) and women born in 1994 or later (n = 348). Twelve high-risk human papillomavirus (HR-HPV) genotypes were detected by Cobas® 4800 HPV test (Roche Diagnostics, Mannheim, Germany). The Linear Array® HPV Genotyping Test (Roche Diagnostics) was used for HR-HPV genotype detection other than HPV 16/18. Information about sexual habits was collected by a self-filled questionnaire. Post-vaccination data were compared to previously published pre-vaccination data obtained between 2008 and 2010 in Galicia from women of the same age (18–26 years old, n = 523). The Stata 14.2 software was employed for statistical analyses.Data from 392 unvaccinated and 353 vaccinated women were compared. For unvaccinated and vaccinated women, HPV 16/18 prevalence was 9.2% and 0.8%, respectively, and HPV 31/33/45 prevalence was 8.4% and 1.1%, respectively. Direct, indirect and total effectiveness of the HPV vaccine were (%, 95% CI): 94 (72−99), 30 (-11−56) and 95 (79−99), respectively, for HPV 16/18 and 83 (46−94), -10 (-88−33) and 84 (54−94), respectively, for HPV 31/33/45. The number of women with first intercourse before 17 years old and 3 or more sexual partners along life was higher in the post-vaccination period (p < 0.05). A positive impact of bivalent HPV vaccine was observed, both on direct and cross protection. Sexual habits could have changed in the post-vaccination period. [ABSTRACT FROM AUTHOR]

Objective: To evaluate both the performance and acceptability of a method coupling self-sampling with detection of cervical malignancy via elevated HPV 16 and 18 E6 oncoproteins (OncoE6™ Cervical Test) in remote areas in Brazil. Methods: Women living in rural villages in proximity to Coari city, Amazonas, Brazil were invited to participate in a cervical cancer screening study. 412 subjects were enrolled; there were no refusals. In addition to E6 protein detection, DNA was extracted from the brushes and evaluated for HPV genotypes by PCR (PGMY09/11), followed by typing by the Papillocheck™ if positive. Subjects who were found to be positive for OncoE6 or HPV-DNA were referred for colposcopy. Results: For 110 subjects (27%) this was the first cervical cancer exam. Overall the HPV-DNA prevalence was 19.1% (n = 79); 1.4% (n = 6) were positive by the OncoE6 Test. Fifty-six women attended the invitation for colposcopy where nine had an abnormal cervix and were subsequently biopsied. Histopathological analysis revealed 2 CIN3, 2 carcinomas and 5 CIN1. OncoE6 called two out of the three HPV 16 or 18 associated CIN3+ lesions. Conclusions: The findings suggest that self-administered sample collection in combination with OncoE6 Test is feasible in this population. This could enable expanded screening coverage while ensuring a high specificity which is imperative given the remote geographic location, since women bearing abnormal test results would necessitate travel and logistical burden to access colposcopy and treatment. [ABSTRACT FROM AUTHOR]

Background: Penile carcinoma (PC) is a rare, highly mutilating disease, common in developing countries. The evolution of penile cancer includes at least two independent carcinogenic pathways, related or unrelated to HPV infection. Objectives: To estimate the prevalence, identify HPV genotypes, and correlate with clinicopathological data on penile cancer. Methods: A retrospective cohort study involving 183 patients with PC undergoing treatment in a referral hospital in Goiânia, Goiás, in Midwestern Brazil, from 2003 to 2015. Samples containing paraffin embedded tumor fragments were subjected to detection and genotyping by INNO-LiPA HPV. The clinicopathological variables were subjected to analysis with respect to HPV positivity and used prevalence ratio (PR), adjusted prevalence ratio (PRa) and 95% confidence interval (CI) as statistical measures. Results: The prevalence of HPV DNA in PC was 30.6% (95% CI: 24.4 to 37.6), high-risk HPV 24.9% (95% CI: 18.9 to 31.3), and 62.5% were HPV 16. There was a statistical association between the endpoints HPV infection and HPV high risk, and the variable tumor grade II-III (p = 0.025) (p = 0.040), respectively. There was no statistical difference in disease specific survival at 10 years between the HPV positive and negative patients (p = 0.143), and high and low risk HPV (p = 0.325). Conclusions: The prevalence of HPV infection was 30.6%, and 80.3% of the genotypes were identified as preventable by anti-HPV quadrivalent or nonavalent vaccine. HPV infections and high-risk HPV were not associated with penile carcinoma prognosis in this study. [ABSTRACT FROM AUTHOR]

Background: High-risk (HR) human papillomavirus (HPV) infection remains a great concern in relation to African men who have sex with men (MSM), especially those infected with HIV. The prevalence of HR-HPV and associated risk factors was estimated in a cross-sectional observational study covering MSM living in Bangui, Central African Republic. Methods: MSM receiving care at the Centre National de Référence des Infections Sexuellement Transmissibles et de la Thérapie Antirétrovirale, Bangui, were included. HIV serostatus and socio-demographic and behavioral characteristics were collected. HPV DNA was detected and genotyped on anal swabs using Anyplex™ II HPV28 test (Seegene, South Korea), and HSV DNA by in-house real-time PCR. Logistic regression analyses were used to determine risk factors associated with HPV outcomes. Results: 42 MSM (mean age, 23.2 years; range, 14–39) including 69.1% HIV-1-positive and 30.9% HIV-negative were prospectively enrolled. The prevalence of anal HPV was 69.1%, including 82.7% of HR-HPV which were multiple in 52.0%. The most prevalent genotypes were HPV-35, HPV-58, HPV-59 and HPV-31. While, HPV-16 and HPV-18 were present in a minority of samples. Multiple HR-HPV infection was more frequent in HIV-positive MSM (41.4%) with 2.7 genotypes per anal samples than in HIV-negative (7.7%) with 1.5 genotypes per anal samples. HPV types included in the prophylactic Gardasil-9® vaccine were detected in 68.9% of specimens and HPV-58 was the most frequently detected. MSM infected by HPV-16 and HPV-18 were all infected by HIV-1. Few anal swabs (11.9%) contained HSV-2 DNA without relationship with HPV detection. Condomless receptive anal intercourse was the main risk factor to being infected with any type of HPV and condomless insertive anal intercourse was significantly less associated with HPV contamination than receptive anal intercourse (Odd ratio = 0.02). Conclusion: MSM in Bangui are at-risk of HIV and HR-HPV anal infections. The unusual distribution of HPV-35 as predominant HPV suggests possible geographic specificities in the molecular epidemiology of HR-HPV in sub-Saharan Africa. Scaling up prevention strategies against HPV infection and related cancers adapted for MSM in Africa should be prioritized. Innovative interventions should be conceived for the MSM population living in Bangui. [ABSTRACT FROM AUTHOR]

Non-Hodgkins lymphoma is most common type of lymphomas, where its typing into B-cell or T-cell types relays on the type of affected cells. it classified into slow growing (low grade or indolent) lymphomas and fast growing (high grade or aggressive) lymphomas. High risk genotypes (HPV) infection is a major risk factor in the carcinogenesis of several tumor .Cyclin-dependent kinase-4 inhibitor (p16/INK4A) is a negative cell cycle regulator, encodes by CDKN2A gene where its expression is most commonly altered due to promoter methylation or homozygous deletion or mutation. Assessing the rates of the expressed protein of P16 tumor suppressor gene and high risk genotype HPV-18 in a patients with Non -Hodgkin's lymphomas. Sixty (60) paraffin embedded lymphatic tissues obtained from 35 patients with non -Hodgkin's lymphomas and 25 apparently healthy lymphatic (control) tissues for the detection of expressed proteins of p16 tumor suppressor gene and HPV-18using an immunohistochemical technique. The HPV-18 positive -IHC reaction was detected in (60%: 21 out of 35 cases) of Non-Hodgkin lymphoma tissues. The P16-immunohistochemical reactions in non -Hodgkin's lymphomatissues were detected in 45.7% (16 out of 35 cases) whereas no positive reaction was revealed in the control tissues. Statistical significant difference was noticed between non - Hodgkin's lymphoma and control tissues groups. The significant rates of HPV-18 and P16 gene expression in the studied non -Hodgkin's lymphomas might point for a role in their carcinogenesis. [ABSTRACT FROM AUTHOR]

Persistent infection with high-risk human papillomavirus (HR-HPV) is necessary for the development of precursor lesions and cervical cancer. HPV infection among women living with HIV/AIDS (WLHA) occurs more frequently, presents a higher rate of persistent infections and an earlier progression to cancer. We aimed to evaluate HR-HPV prevalence, incidence and clearance, and its association with HIV viral suppression, immunological response and other risk factors among WLHA followed at an STD/HIV reference center. This was a cohort study conducted at a reference center for STD/AIDS in Northeastern Brazil from September 2013 to September 2015. Follow-up visits were conducted at 6 and 12 months after enrolment, where socio-epidemiological data were obtained. Cervical samples were collected for conventional cytology and HPV DNA research (PCR COBAS® Roche) in addition to blood samples for CD4+ T lymphocyte count and HIV viral load. We prospectively evaluated 333 women. HR-HPV DNA prevalence was 33.3% at baseline. HPV-16 was present in 5.1%, HPV-18 in 3.9% and 29.4% WLHA had other HR-HPV (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68). The HR-HPV incidence during the follow-up was 10.8%, at the 6-month visit was 7.7% and at the 12-month visit was 3.7%. Variables associated with HR-HPV incidence were: nulliparity, combined oral contraceptive use and detectable HIV viral load. The HR-HPV clearance rate was 41.7% and was associated with age >30 years and lymphocyte T CD4 count >500 cells/mm3 at enrolment. These findings contribute to the knowledge about a group of women that need more careful HPV screening and describe the association between an efficient immunological response and HIV viral suppression with lower incidence and increased clearance of HR-HPV. [ABSTRACT FROM AUTHOR]

Background: Invasive cervical cancer (ICC) is the third most common malignant neoplasm affecting Brazilian women. Little is known about the impact of specific HPV genotypes in the prognosis of ICC. We hypothesized that HPV genotype would impact ICC clinical presentation and survival. Methods: Women diagnosed with ICC at the Instituto do Câncer do Estado de São Paulo (ICESP) between May 2008 and June 2012 were included in the study and were followed until December 2015. HPV genotype was detected from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples using Onclarity™ system (BD Viper™ LT automated system). Results: 292 patients aged 50±14 years were analyzed. HPVDNA was detected in 84% of patients. The HPV genotypes studied were: HPV16 (64%), HPV18 (10%), HPV33-58 (7%), HPV45 (5%), HPV31 (4%) and other high-risk HPV genotypes (11%). HPV genotypes showed different distributions regarding histological type and clinical stage. Patients were followed for 35±21 months. The overall survival at 5 years after diagnosis of cervical cancer was 54%. Age, clinical staging, histological type and multiple HPV genotypes infection detected in the same tumor specimen were associated with poorer overall survival on multivariate Cox proportional hazard analysis (p<0.05). No specific HPV genotype affected survival. Conclusion: Multiple HPV genotype infection was associated with poorer ICC survival in our study, compared with single genotype infection. HPV genotyping from FFPE tumor tissue using an automated assay such as the Onclarity BD™ assay provides a simpler alternative for routine clinical use. Impact: This is the largest study employing an automated HPV genotyping assay using FFPE of ICC. Multiple HPV genotype infection adversely influenced survival. [ABSTRACT FROM AUTHOR]

Background: Polymerase chain reaction-based Xpert human papillomavirus (HPV) assay is a rapid test that detects high-risk HPV (hrHPV) infection. This point-of-care test is usually performed by collecting a cervical specimen in a vial of PreservCyt® transport medium. We compared HPV test positivity and accuracy between self-collected sample with a dry swab (s-DRY) versus physician-collected cervical sampling using a broom like brush and immediate immersion in PreservCyt (dr-WET). Methods: In this cross-sectional study, we recruited 150 women ≥ 18 years old attending the colposcopy clinic in the University Hospital of Geneva. Each participant first self-collected a vaginal sample using a dry swab and then the physician collected a cervical specimen in PreservCyt. HPV analysis was performed with Xpert. Part of the PreservCyt-collected sample was used for hrHPV detection with the cobas® HPV test. HPV test positivity and performance of the two collection methods was compared. Results: HPV positivity was 49.1% for s-DRY, 41.8% for dr-WET and 46.2% for cobas. Good agreement was found between s-DRY and dr-WET samples (kappa±Standard error (SE) = 0.64±0.09,), particularly for low-grade squamous intraepithelial lesions (LSIL+) (kappa±SE = 0.80±0.17). Excellent agreement was found between the two samples for HPV16 detection in general (kappa±SE = 0.91±0.09) and among LSIL+ lesions (kappa±SE = 1.00±0.17). Sensitivities and specificities were, respectively, 84.2% and 47.1%(s-DRY), 73.1% and 58.7%. (dr-WET) and 77.8% and 45.7% (cobas) for CIN2+ detection. The median delay between sampling and HPV analysis was 7 days for the Xpert HPV assay and 19 days for cobas. There were 36 (24.0%) invalid results among s-DRY samples and 4 (2.7%) among dr-WET (p = 0.001). Invalid results happened due to the long interval between collection and analysis. Conclusion: Self-collected vaginal dry swabs are a valid alternative to collecting cervical samples in PreservCyt solution for HPV testing with the Xpert HPV assay. Impact: HPV self-collection with dry cotton swabs might assist in the implementation of an effective screening strategy in developing countries. Trial registration: International Standard Randomized Controlled Trial Number Registry [ABSTRACT FROM AUTHOR]

Aim of the study: To assess the feasibility of partial HPV genotyping and methylation analysis of CADM1, MAL, and miR124-2 genes as triage tests in assaying self-collected cervical samples positive for high-risk HPV on primary screening, and to review the literature regarding host cellular gene methylation analysis of self-collected cervical samples. Material and methods: Women residing in North-East Italy who had failed to respond to the invitation to participate in an organized population-based program were invited to provide a self-sample. Their stored baseline (self-collected) and follow-up (clinician-collected) cervical samples were included in the study. DNA was extracted from HPV-positive (Qiagen’s Hybrid Capture 2, HC2) samples. Partial genotyping with separate detection of HPV types 16 and 18 was performed with a hybrid capture-based method and a quantitative PCR assay. Methylation was assayed with a quantitative methylation-specific PCR. Results: High-risk HPV infection was detected in 48% of baseline and 71% of follow-up HC2-positive samples. Methylation was demonstrated respectively in 15% and 23.5% of baseline and follow-up samples and chiefly involved a single gene (miR124-2). Invalid quantitative PCR results were recorded in 5% of self-collected samples. The specificity of miR124-1, MAL, and CADM1 methylation was 84%, 94%, and 98%, respectively, and the specificity of the three markers combined was 84%. Sensitivity was not estimated due to the lack of CIN2+ samples. The systematic review showed that different methylation assays yield different accuracy values. Conclusion: Self-collected samples are suitable for methylation assays included in reflex triage testing. The reproducibility and accuracy of the methylation tests described in the literature should be improved. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is one of the most common and lethal cancers in West Africa. Even though vaccines that protect against the most common Human papillomavirus (HPV) strains, 16 and 18, are currently in use in developed countries, the implementation of these vaccines in developing countries has been painfully slow, considering the pre-eminence of HPV-associated cervical cancer among women in those countries. Aim: We performed serological and PCR-based assessment of blood and tissue specimens obtained from women undergoing cervical cancer-related surgery at a major urban hospital in Bamako. Since several therapeutic HPV vaccines are currently in clinical trials, we also assessed willingness to participate in HPV cancer vaccine trials. Methods: Blood and biopsy samples of 240 women were evaluated for HPV types 16 and 18 by serology and PCR. Knowledge regarding the HPV vaccine and autonomy to decide to vaccinate their own child was assessed with a standardized questionnaire. Results: HPV 16 and 18 were identified in 137/166 (82.5%) cervical cancer biopsy samples by PCR. Co-infection with both HPV 16 and 18 was significantly more frequent in women over 50 years of age than in younger women (63.0% vs. 37.0%). 44% of study participants said they would be willing to vaccinate their child with HPV vaccine. Only 39% of women participating in this study reported that they would be able to make an autonomous decision to receive HPV vaccination. Permission from a male spouse or head of household was identified as important for participation by 59% of the women. Conclusion: This study provides strong support for the introduction of currently available HPV vaccines in Mali, and also provides key information about conditions for obtaining informed consent for HPV vaccine trials and HPV vaccination in Mali. [ABSTRACT FROM AUTHOR]

Immunochromatography (IC) is widely used to detect target molecules in biological fluids. Since this method can be performed without a special technique or device, IC is a convenient way to assess the existence of antibodies or pathogens such as viruses and bacteria, simply and quickly. In this study, we established an IC method to detect serum antibodies against oncogenic human papillomavirus (HPV)-16 and HPV-18 L1 proteins using recombinant L1 proteins produced by silkworms as antigens. Infection of oncogenic HPVs is a major risk factor of cervical cancer, which is one of the most common cancers in women worldwide. We first measured blood sera of two groups by magnetic beads enzyme-linked immunosorbent assay (MB-ELISA). For the first group, sera were collected prospectively from young women who planned to receive HPV vaccination. The second group consisted of children under 20 years of age, non-vaccinated healthy women, vaccinated healthy women, dysplasia, cervical intraepithelial neoplasia III, and cervical cancer patients. We confirmed that standard vaccination doses significantly increased serum HPV antibody concentrations, and the level was sustained at least more than 30 months after vaccination. In contrast, an increase in antibody concentration was not observed in patients with precancerous cervical changes and cervical cancer. We next measured the samples in both groups using the IC method we originally developed, and found that the measurement values of IC highly correlated with those of MB-ELISA. The simple and quick IC method would be a useful tool for rapid monitoring of L1 specific antibody levels in a non-laboratory environment. With less than one drop of serum, our IC can easily detect serum HPV-16/-18 antibodies within 15 minutes, without the need for electronic devices or techniques. [ABSTRACT FROM AUTHOR]

We describe a novel microarray based-method for the screening of oncogenic human papillomavirus 18 (HPV-18) molecular variants. Due to the fact that sequencing methodology may underestimate samples containing more than one variant we designed a specific and sensitive stacking DNA hybridization assay. This technology can be used to discriminate between three possible phylogenetic branches of HPV-18. Probes were attached covalently on glass slides and hybridized with single-stranded DNA targets. Prior to hybridization with the probes, the target strands were pre-annealed with the three auxiliary contiguous oligonucleotides flanking the target sequences. Screening HPV-18 positive cell lines and cervical samples were used to evaluate the performance of this HPV DNA microarray. Our results demonstrate that the HPV-18’s variants hybridized specifically to probes, with no detection of unspecific signals. Specific probes successfully reveal detectable point mutations in these variants. The present DNA oligoarray system can be used as a reliable, sensitive and specific method for HPV-18 variant screening. Furthermore, this simple assay allows the use of inexpensive equipment, making it accessible in resource-poor settings.

The objective of this study is to understand the structural flexibility and curvature of the E2 protein of human papillomavirus type 18 using molecular dynamics (6 ns). E2 is required for viral DNA replication and its disruption could be an anti-viral strategy. E2 is a dimer, with each monomer folding into a stable open-faced β-sandwich. We calculated the mobility of the E2 dimer and found that it was asymmetric. These different mobilities of E2 monomers suggest that drugs or vaccines could be targeted to the interface between the two monomers.

Objective: To examine the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) infections in relation to age of patients with cervical adenocarcinoma. Materials and Methods: Thirty samples of human cervical adenocarcinoma tissue were collected from the surgical pathology archive at Taipei Veterans General Hospital from 1996 to 2008. All samples were examined for EBV, HPV-16 and HPV-18 E6 DNA by conventional and real-time quantitative polymerase chain reaction assays. Results: HPV-16 DNA was detected in 10 cases (33.3%), HPV-18 DNA in 12 cases (40%), and EBV DNA in three cases (10%); there were negative findings in seven cases (23.3%). EBV combined with HPV-16 or HPV-18 was also detected in one case each. No link could be demonstrated between HPV and EBV in endocervical lesions. When 20 patients £ 45 years old were compared with 10 patients > 45 years old, HPV-18 E6 DNA was detected in 45% vs. 30% (9/20 vs. 3/10), HPV-16 E6 DNA in 40% vs. 20% (8/20 vs. 2/10), EBV DNA in 10% vs. 10% (2/20 vs. 1/10), and no virus DNA was detected in 10% vs. 50% (2/20 vs. 5/10). HPV and EBV were significantly more common in younger women (p < 0.001). Conclusion: HPV-18 plays a major role in adenocarcinomas at any age. A high prevalence of HPV DNA is significantly associated with cervical adenocarcinoma, especially in younger women. The results do not support a role for EBV in cervical adenocarcinogenesis or any relationship between EBV and HPV infection in adenocarcinoma.

Background The causal association between human papillomavirus (HPV) and oral squamous cell carcinoma (OSCC) remains controversial. Most of previous studies did not consider the potential modification effect of sexual behaviors when evaluating the role of HPV infection in OSCC risk. Objectives To explore the independent and joint effects of oral HPV infection and sexual behaviors on OSCC in Chinese population. Study design A case-control study was conducted from September 2012 to September 2015 in Fujian, China. HPV DNA genotypes were detected in tumor tissues of 178 OSCC patients and oral exfoliated cells of 189 frequency-matched controls using flow-through hybridization and gene chip. Epidemiologic data were collected with a structured questionnaire by face-to-face interviews. Odds ratios (ORs) and 95% confidence interval (CI) were estimated with unconditional logistic regression models. Results The overall HPV prevalence was 14.04% in OSCC patients and 3.17% in controls. HPV-18 was the most prevalent type in cases and controls (10.67% vs. 2.12%). Oral HPV infection was strongly associated with an increased risk of OSCC: the ORs were 7.21 (95% CI: 2.61–19.88) for HPV16/18 and 7.59 (95% CI: 2.34–24.64) for HPV-18. Moreover, the significant associations were only observed in females, young adults, married population, merchants, non-smokers, non-alcohol drinkers and non-tea drinkers. Additionally, the first intercourse below 22 years of age and oral sex practice did not show an association with OSCC. But there was a significantly multiplicative interaction between HPV 16/18 and age at first intercourse for OSCC ( P interaction < 0.001). Conclusions Oral HPV infection (specifically type 18) is an independent risk factor for OSCC in Fujian area. Furthermore, there might be a combined effect of HPV 16/18 and age at first intercourse on OSCC. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Recently a 9-valent HPV (9vHPV) prophylactic vaccine was licensed. Seroprevalence prior to vaccine dissemination is needed for monitoring vaccine effectiveness over time. Few studies have assessed the seroprevalence of 9vHPV types in men. Objectives: To investigate the seroprevalence of 9vHPV vaccine types and associated risk factors among men residing in Brazil, Mexico, and the United States. Methods: Six hundred men were randomly selected from the HPV Infection in Men (HIM) Study. Archived serum specimens collected at enrollment were tested for antibodies against nine HPV types (6, 11, 16, 18, 31, 33, 45, 52 and 58) using a glutathione S-transferase (GST) L1-based multiplex serologic assay. Socio-demographic, lifestyle and sexual behavior data at enrollment were collected through a questionnaire. Binomial proportions were used to estimate seroprevalence and logistic regression was used to examine factors associated with seropositivity of type-specific and grouped (i.e. 9vHPV, high-risk 9vHPV, low risk 9vHPV, and five-additional) HPV types. Results: Overall, 28.3% of men were seropositive for at least one of the 9vHPV vaccine types, 14.0% for at least one of the seven high-risk types (16, 18, 31, 33, 45, 52 and 58) and 11.2% for at least one of the five high-risk types (31, 33, 45, 52 and 58) not included in the quadrivalent HPV vaccine, and 17.4% for at least one of the low-risk types (6/11). In multivariate analyses, odds ratios adjusted (AOR) for country of residence, age, marital status, smoking, number of anal sex lifetime partners, compared to men with no anal sex lifetime partners, men with ≥2 partners were more likely to be seropositive for grouped HPV [(9vHPV: AOR 2.52; 95% confidence interval (CI) 1.40–4.54), (high-risk 9vHPV: AOR 2.18; 95%CI: 1.05–4.50) and (low-risk 9vHPV: AOR 2.12; 95%CI: 1.12–4.03)], and individual HPV types 6, 16, 33 and 58 with AORs ranging from 2.19 to 7.36. Compared to men aged 18–30 years, men older than 30 years were significantly more likely to be seropositive for any high-risk 9vHPV, in addition to individual types 18 and 45; and compared to never smokers, current smokers were more likely to be seropositive to 9vHPV, low-risk 9vHPV and HPV 6. In contrast, married men were less likely to be seropositive to any high-risk 9vHPV and individual HPV types 18 and 31 when compared to single men. Conclusions: These data indicate that exposure to the nine HPV types included in the 9vHPV vaccine is common in men and that seropositivity to 9vHPV vaccine types is associated with older age and the lifetime number of anal sex partners. Nine valent HPV vaccination of males and females has the potential to prevent HPV related diseases and transmission in both sexes. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus type 18 is the second most common cause of cervical cancer and is found in 7 to 20 % of cases of cervical cancer. The oncogenic potential of high-risk human papillomavirus is associated with expression of early proteins E6 and E7. Due to long-term immunosuppressive therapy, renal transplant recipients have a higher risk of developing persistent human papillomavirus infection. Case presentation: A 29-year-old white woman from Latvia with chronic focal segmental glomerulosclerosis received renal allograft transplantation and was prescribed immunosuppressive therapy with cyclosporine, prednisolone, and mycophenolate mofetil. Two weeks after renal transplantation, her cervical swab was positive for human papillomavirus consensus sequences. After 6 months, quantitative polymerase chain reaction showed a high viral load of 3,630,789 copies/105 cells of high-risk human papillomavirus type 18 and expression of E6 and E7 oncogenes in her cervical swab and urine sample. One year after renal transplantation, the viral load in her cervical swab increased significantly to 7,413,102 copies/105 cells. Messenger ribonucleic acid of human papillomavirus type 18 E6 and E7 oncogenes were also detected. Shortly after this, she had an unsuccessful pregnancy which resulted in a spontaneous abortion at 6/7 weeks. Two months after the abortion her viral load sharply decreased to 39 copies/105 cells. Oncogenes E6 and E7 messenger ribonucleic acid expression was not observed in this period. Conclusions: This case report represents data which show that immunosuppressive therapy may increase the risk of developing persistent high-risk human papillomavirus infection with expression of E6 and E7 oncogenes in renal transplant recipients. However, even during this therapy the immune status of a recipient can improve and contribute to human papillomavirus viral load reduction. Spontaneous abortion can be considered a possible contributory factor in human papillomavirus clearance. [ABSTRACT FROM AUTHOR]

A subset of high-risk Human Papillomaviruses (HPVs) are the causative agents of a large number of human cancers, of which cervical is the most common. Two viral oncoproteins, E6 and E7, contribute directly towards the development and maintenance of malignancy. A characteristic feature of the E6 oncoproteins from cancer-causing HPV types is the presence of a PDZ binding motif (PBM) at its C-terminus, which confers interaction with cellular proteins harbouring PDZ domains. Here we show that this motif allows E6 interaction with Sorting Nexin 27 (SNX27), an essential component of endosomal recycling pathways. This interaction is highly conserved across E6 proteins from multiple high-risk HPV types and is mediated by a classical PBM-PDZ interaction but unlike many E6 targets, SNX27 is not targeted for degradation by E6. Rather, in HPV-18 positive cell lines the association of SNX27 with components of the retromer complex and the endocytic transport machinery is altered in an E6 PBM-dependent manner. Analysis of a SNX27 cargo, the glucose transporter GLUT1, reveals an E6-dependent maintenance of GLUT1 expression and alteration in its association with components of the endocytic transport machinery. Furthermore, knockdown of E6 in HPV-18 positive cervical cancer cells phenocopies the loss of SNX27, both in terms of GLUT1 expression levels and its vesicular localization, with a concomitant marked reduction in glucose uptake, whilst loss of SNX27 results in slower cell proliferation in low nutrient conditions. These results demonstrate that E6 interaction with SNX27 can alter the recycling of cargo molecules, one consequence of which is modulation of nutrient availability in HPV transformed tumour cells. [ABSTRACT FROM AUTHOR]

The high-risk Human Papillomavirus (HPV) E6 oncoproteins are characterised by the presence of a class I PDZ-binding motif (PBM) on their extreme carboxy termini. The PBM is present on the E6 proteins derived from all cancer-causing HPV types, but can also be found on some related non-cancer-causing E6 proteins. We have therefore been interested in investigating the potential functional differences between these different E6 PBMs. Using an unbiased proteomic approach in keratinocytes, we have directly compared the interaction profiles of these different PBMs. This has allowed us to identify the potential PDZ target fingerprints of the E6 PBMs from 7 different cancer-causing HPV types, from 3 HPV types with weak cancer association, and from one benign HPV type that possesses an ancestral PBM. We demonstrate a striking increase in the number of potential PDZ targets bound by each E6 PBM as cancer-causing potential increases, and show that the HPV-16 and HPV-18 PBMs have the most flexibility in their PDZ target selection. Furthermore, the specific interaction with hScrib correlates directly with increased oncogenic potential. In contrast, hDlg is bound equally well by all the HPV E6 PBMs analysed, indicating that this is an evolutionarily conserved interaction, and was most likely one of the original E6 PBM target proteins that was important for the occupation of a potential new niche. Finally, we present evidence that the cell junction components ZO-2 and β-2 syntrophin are novel PDZ domain–containing targets of a subset of high-risk HPV types. [ABSTRACT FROM AUTHOR]

A phenotypic high-throughput cell culture screen was performed to identify compounds that prevented proliferation of the human Papilloma virus type 16 (HPV-16) transformed cell line Ca Ski. A series of quinoxaline compounds exemplified by Compound 1 was identified. Testing against a panel of cell lines demonstrated that Compound 1 selectively inhibited replication of all HPV-16, HPV-18, and HPV-31 transformed cell lines tested with 50% Inhibitory Concentration (IC50) values of 2 to 8 μM relative to IC50 values of 28 to 73 μM in HPV-negative cell lines. Treatment with Compound 1 resulted in a cascade of multiple apoptotic events, including selective activation of effector caspases 3 and 7, fragmentation of cellular DNA, and PARP (poly(ADP-ribose) polymerase) cleavage in HPV-positive cells relative to HPV-negative cells. Unregulated proliferation of HPV transformed cells is dependent on the viral oncogenes, E6 and E7. Treatment with Compound 1 resulted in a decrease in HPV E7 protein in Ca Ski cells. However, the timing of this reduction relative to other effects of compound treatment suggests that this was a consequence, rather than a cause, of the apoptotic cascade. Likewise, compound treatment resulted in no obvious effects on the E6- and E7- mediated down regulation of p53 and Rb, or their downstream effectors, p21 or PCNA. Further investigation of apoptotic signals induced by Compound 1 revealed cleavage of Caspase-8 in HPV-positive cells as early as 2 hours post-treatment, suggesting the compound initiates apoptosis through the extrinsic, death receptor-mediated, pathway of cell death. These studies provide proof of concept that cells transformed by oncogenic Papillomaviruses can be selectively induced to undergo apoptosis by compound treatment. [ABSTRACT FROM AUTHOR]

Objectives: Intratypic molecular variants of human papillomavirus (HPV) type-16 and -18 exist. In the Netherlands, a bivalent vaccine, composed of recombinant L1 proteins from HPV-16 and -18, is used to prevent cervical cancer since 2009. Long-term vaccination could lead to changes in HPV-16 and -18 virus population, thereby hampering vaccination strategies. We determined the genetic diversity of the L1 gene in HPV-16 and -18 viral strains circulating in the Netherlands at the start of vaccination in order to understand the baseline genetic diversity in the Dutch population. Methods: DNA sequences of the L1 gene were determined in HPV-16 (n = 241) and HPV-18 (n = 108) positive anogenital samples collected in 2009 and 2011 among Dutch 16- to 24-year old female and male attendees of the sexually transmitted infection (STI) clinics. Phylogenetic analysis was performed and sequences were compared to reference sequences HPV-16 (AF536179) and HPV-18 (X05015) using BioNumerics 7.1. Results: For HPV-16, ninety-five single nucleotide polymorphism (SNPs) were identified, twenty–seven (28%) were non-synonymous variations. For HPV-18, seventy-one SNPs were identified, twenty-nine (41%) were non-synonymous. The majority of the non-silent variations were located in sequences encoding alpha helix, beta sheet or surface loops, in particular in the immunodominant FG loop, and may influence the protein secondary structure and immune recognition. Conclusions: This study provides unique pre-vaccination/baseline data on the genetic L1 diversity of HPV-16 and -18 viruses circulating in the Netherlands among adolescents and young adults. [ABSTRACT FROM AUTHOR]

Background: Reported human papillomavirus (HPV) vaccination coverage in England is high, particularly in girls offered routine immunisation at age 12 years. Serological surveillance can be used to validate reported coverage and explore variations within it and changes in serological markers over time. Methods: Residual serum specimens collected from females aged 15–19 years in 2010–2011 were tested for anti-HPV16 and HPV18 IgG by ELISA. Based on these results, females were classified as follows: seronegative, probable natural infection, probable vaccine-induced seropositivity, or possible natural infection/possible vaccine-induced seropositivity. The proportion of females with vaccine-induced seropositivity was compared to the reported vaccination coverage. Results: Of 2146 specimens tested, 1380 (64%) were seropositive for both types HPV16 and HPV18 and 159 (7.4%) positive for only one HPV type. The IgG concentrations were far higher for those positive for both HPV types than those positive for only one HPV type. 1320 (62%) females were considered to have probable vaccine-induced seropositivity. Among vaccine-induced seropositives, antibody concentrations declined with increasing age at vaccination and increasing time since vaccination. Conclusions: The proportion of females with vaccine-induced seropositivity was closest to the reported 3-dose coverage in those offered the vaccination at younger ages, with a greater discrepancy in the older females. This suggests either some under-reporting of immunisations of older females and/or that partial vaccination (i.e. one- or two-doses) has provided high antibody responses in 13–17 year olds. [ABSTRACT FROM AUTHOR]

A brief historical background on Autism & some of the important symptoms associated with Autism are summarized. Using strong Electro Magnetic Field Resonance Phenomenon between 2 identical molecules with identical weight (which received U.S. Patent) non-invasively & rapidly we can detect various molecules including neurotransmitters, bacteria, virus, fungus, metals & abnormal molecules. Simple non-invasive measurement of various molecules through pupils & head of diagnosed or suspected Autism patients indicated that in Autism patients following changes were often found: 1) Acetylcholine is markedly reduced; 2) Alzheimer's disease markers (i.e. β-Amyloid (1-42), Tau Protein, Apolipoprotein (Apo E4)) are markedly increased; 3) Chrysotile Asbestos is increased; 4) Titanium Dioxide (TiO2) is moderately increased; 5) A1 is moderately increased; 6) Hg is moderately increased; 7) Dopamine, Serotonin & GAB A are significantly reduced (up to about 1/10 of normal); 8) Often viral infections (such as CMV, HHV-6, E1PV-16, HPV-18, etc.), and Bacterial infections (such as Chlamydia trachomatis, Mycobacterium TB, Borrelia Burgdorferi, etc.) coexist. Research by others on Autism spectrum disorder (ASD) shows that it is a group of complex neurodevelopmental disorders, with about 70% of ASD patients also suffering from gastro-intestinal problems. While Alzheimer disease (AD) is characterized by formation of 1) Amyloid plaques, 2) Neurofibrillary tangles inside of neurons, and 3) Loss of connections between neurons. More than 90% of AD develops in people over the age of 65. These 3 characteristics often progressively worsen over time. Although Autism Spectrum Disorder and Alzheimer's disease are completely different diseases they have some similar biochemical changes. Eight examples of such measurement & analysis are shown for comparison. Most of Autism patients improved significantly by removing the source or preventing intake of Asbestos, TiO2, A1 & Hg or enhancing urinary output of above abnormal substances & coexisting infections, if treatment is given early. When HPV-16 & HPV-18 coexist, at triangular central area of the top of head, in addition to inability to talk, severe neuromuscular problems of lower extremity were found to also exist. However, if treatment is given 3-4 years after onset of Autism symptoms, even when successful biochemical reduction of above abnormal substances occurs, clinical improvement is less significant, since permanent damage in brain tissue seems to already exist. Therefore, early diagnosis & early treatment is very important for both Autism & Alzheimer's disease. In addition the optimal doses of Vitamin D3 and Taurine may play an important role in the future treatment of Autism, Alzheimer's Disease and memory disturbances by significantly increasing Acetylcholine and DHEA levels, enhancing the excretion of toxic substances in the urine, as well as having an anticancer effect. [ABSTRACT FROM AUTHOR]

Background. Circumcision and lower human papillomavirus (HPV) viral loads in men are possibly associated with a reduced risk of HPV transmission to women. However, the association between male circumcision and HPV viral load remains unclear.Methods. Swab specimens from the glans and shaft of the penis were collected from men enrolled in a circumcision trial in Kisumu, Kenya. GP5+/6+ polymerase chain reaction (PCR) was used to identify HPV DNA types. HPV-16 and HPV-18 loads were measured with a LightCycler real-time PCR and classified as high (>250 copies/scrape) or low (≤250 copies/scrape).Results. A total of 1159 men were randomly assigned to undergo immediate circumcision, and 1140 men were randomly assigned to the control arm (these individuals were asked to remain uncircumcised until the study ended). The hazard of acquisition of high-viral load infections in the glans was lower in the circumcision arm, compared with the control arm, for HPV-16 (hazard ratio [HR], 0.32 [95% confidence interval {CI}, .20–.49]) and HPV-18 (HR, 0.34 [95% CI, .21–.54]). The 6-month risk of HPV persistence among men with high-viral load infections in the glans at baseline was lower in the circumcision arm, compared with the control arm, for HPV-16 (risk ratio [RR], 0.36 [95% CI, .18–.72]) and HPV-18 (RR 0.34 [95% CI, .13–.86]). Weaker and less precise results were obtained for shaft samples.Conclusions. Male circumcision could potentially reduce the risk of HPV transmission to women by reducing the hazard of acquisition, and the risk of persistence of high-HPV viral load infections in the glans in men. [ABSTRACT FROM PUBLISHER]

Purpose: The quadrivalent HPV vaccination was approved for use in males ages 9 to 26 in 2009 and recommended for routine administration in 2011. The purpose of this study was to uncover predictable commonalities amongst parents who chose to vaccinate their 11–17 year old sons against HPV. Methods: We compiled data from a U.S. national sample of 779 parents with sons 11–17 years old using a web-based survey to gather information about behavioral and sociodemographic factors which predicted receipt of 1 or more HPV vaccine doses based on parental report. Predictors were first modeled individually for univariable associations. Significant predictors (p<0.10) were combined in a multivariable model. Results: In the adjusted model, independent predictors included receipt of flu vaccination, health insurance coverage and sexual health topic discussions with sons. Sons who had received a flu shot in the last two years more frequently received at least one dose of the vaccine (OR 1.82; 95% CI 1.45–2.26). Sons covered by private health insurance had decreased odds of HPV vaccination (OR 0.56 95% CI 0.37–0.83). Lastly, parents who had discussed sexual health topics with their sons were more likely to vaccinate (OR 1.61; 95% CI 1.37–1.89). Conclusions: Male vaccination rates in the U.S. have increased, but males continue to be under-immunized. Utilization of health care is an important factor in HPV vaccine uptake; therefore, health care providers should use every contact as an opportunity to vaccinate. Communication about sexual health topics may provide a forum for parents and health care providers to have conversations about HPV vaccination as those more comfortable discussing these topics may also be more comfortable discussing HPV vaccination. [ABSTRACT FROM AUTHOR]

Background: In Norway, repeat cytology and HPV testing comprise delayed triage of women with minor cytological lesions. The objective of this study was to evaluate HPV DNA and HPV mRNA testing in triage of women with an ASC-US/LSIL diagnosis. Materials and Methods: We used repeat cytology, HPV DNA testing (Cobas 4800) and HPV mRNA testing (PreTect HPV-Proofer) to follow up 311 women aged 25–69 years with ASC-US/LSIL index cytology. Results: Of 311 women scheduled for secondary screening, 30 women (9.6%) had ASC-H/HSIL cytology at triage and 281 women (90.4%) had ASC-US/LSIL or normal cytology. The HPV DNA test was positive in 92 (32.7%) of 281 instances, and 37 (13.2%) were mRNA positive. Of the 132 women with repeated ASC-US/LSIL, we received biopsies from 97.0% (65/67) of the DNA-positive and 92.9% (26/28) of the mRNA-positive cases. The positive predictive values for CIN2+ were 21.5% (14/65) for DNA positive and 34.6% (9/26) for mRNA positive (ns). The odds ratio for being referred to colposcopy in DNA-positive cases were 2.8 times (95% CI: 1.8–4.6) higher that of mRNA-positive cases. Compared to the mRNA test, the DNA test detected four more cases of CIN2 and one case of CIN3. Conclusions: The higher positivity rate of the DNA test in triage leads to higher referral rate for colposcopy and biopsy, and subsequent additional follow-up of negative biopsies. By following mRNA-negative women who had ASC-US/LSIL at triage with cytology, the additional cases of CIN2+ gained in DNA screening can be discovered. Our study indicates that in triage of repeated ASC-US/LSIL, HPV mRNA testing is more specific and is more relevant in clinical use than an HPV DNA test. [ABSTRACT FROM AUTHOR]

Each year more than 159,000 new cases of laryngeal cancer are diagnosed globally, and more than 9000 patients die due to this malignancy. Viral infections are a known risk factor for this malignancy. Thus, this study aimed to evaluate the role of HPV-16/18 and HHV-8 infection in patients with laryngeal cancer. In this case–control study, 60 formalin-fixed, paraffin-embedded samples of laryngeal cancer and 22 normal larynx tissue samples from the Pathology Department of Qaem Hospital, Mashhad, Iran were studied. After validating the diagnosis, the samples were evaluated for the detection of HPV-16/18 and HHV-8 DNA using PCR technique. The data were registered and analyzed using SPSS 18.0. The average age for patients and controls was 61.29±11.89 and 55.77±10.10, respectively. Fifty-four patients (90%) and 16 (72.7%) controls were male. PCR results detected no HPV-16/18 DNA in both groups. Although there were 2 positive HHV-8 samples in both laryngeal cancer and normal larynx samples, no significant relation was present (p =0.291). We found no significant relationship between infection with HHV-8 or HPV-16/18 and the existence of laryngeal cancer. However, more complementary studies are required to re-evaluate our results using more samples and better viral detection techniques. [ABSTRACT FROM AUTHOR]