Low-risk High-risk Human Papillomavirus Research Articles

Incidence of pre-neoplastic and neoplastic lesions of the cervix before and after the COVID-19 pandemic

ObjectiveThe COVID-19 pandemic had significant effects on healthcare systems worldwide, including the disruption of routine screening programs for cervical cancer. This study aimed to compare the incidence of cervical intra-epithelial...

Association between Dietary Vitamin E Intake and Human Papillomavirus Infection among US Adults: A Cross-Sectional Study from National Health and Nutrition Examination Survey.

Persistent high-risk human papillomavirus (HPV) infection is responsible for most genital, anal, and oropharyngeal cancers, in which men contribute significantly to infection and subsequent tumorigenesis in women. Vitamin E has been shown to be associated with vaginal HPV infection and cervical cancer. However, the association of vitamin E consumption with HPV infection among the overall population remains unclear. We investigate the association between vitamin E consumption and genital and oral HPV infection in both men and women. We used cross-sectional data from the National Health and Nutrition Examination Survey between 2013 and 2016 to collect details on their dietary vitamin E intake, genital and oral HPV infection status, and other essential variables. In total, 5809 participants aged 18-59 years were identified, with overall prevalence of high-risk and low-risk HPV infection of 23.7% and 21.1%, respectively. Compared with the lowest vitamin E group Q1 (<5.18 mg/day), the adjusted OR for vitamin E consumption and overall high-risk HPV infection in Q2 (5.18-7.54 mg/day), Q3 (7.55-10.82 mg/day), and Q4 (>10.82 mg/day) were 0.91 (95% CI: 0.81-1.03, p = 0.134), 0.77 (95% CI: 0.69-0.87, p < 0.001), and 0.72 (95% CI: 0.65-0.80, p < 0.001), respectively. Restricted cubic spline regression showed a linear relationship between vitamin E consumption and overall high-risk HPV infection. This linear relationship also existed for vitamin E consumption and overall low-risk HPV infection. After being stratified by gender and site, vitamin E consumption was inversely related to vaginal low- and high-risk HPV infection, penile high-risk HPV infection, and male oral low-risk HPV infection. In conclusion, we identified inverse linear relationships between dietary vitamin E intake and overall high- and low-risk HPV infection. Future well-designed longitudinal studies are still required to validate the impact of vitamin E on HPV carcinogenesis.

Malignancy Associated with Low-Risk HPV6 and HPV11: A Systematic Review and Implications for Cancer Prevention.

High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0-5.5% for penile and 0-87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the E7 gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV.

Development of a simplified and cost-effective sample preparation method for genotyping of human papillomavirus by next-generation sequencing.

High-risk human papillomavirus (HPV) infection is the most common cause of cervical cancer, but low-risk HPV strains can sometimes also be involved. Although HPV genotyping techniques used in clinical diagnosis cannot detect low-risk HPV, next-generation sequencing (NGS) can detect both types. However, DNA library preparation is complicated and expensive. The aim of this study was to develop a simplified, cost-effective sample preparation procedure for HPV genotyping based on next-generation sequencing (NGS). After DNA extraction, a first round of PCR was performed using modified MY09/11 primers specific for the L1 region of the HPV genome, followed by a second round of PCR to add the indexes and adaptors. Then, the DNA libraries were purified and quantified, and high-throughput sequencing was performed using an Illumina MiSeq platform. The sequencing reads were compared with reference sequences for HPV genotyping. The limit of detection for HPV amplification was 100 copies/µl. Analysis of the correlation of pathological cytology with the HPV genotype in individual clinical samples showed that HPV66 was the most common genotype found in the normal stage, whereas HPV16 was the main genotype found in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and cervical cancer. This NGS method can detect and identify several HPV genotypes with 92% accuracy and 100% reproducibility, and it shows potential as a simplified and cost-effective technique for large-scale HPV genotyping in clinical samples.

False Negative Results in Cervical Cancer Screening-Risks, Reasons and Implications for Clinical Practice and Public Health.

False negative (FN) results in cervical cancer (CC) screening pose serious risks to women. We present a comprehensive literature review on the risks and reasons of obtaining the FN results of primary CC screening tests and triage methods and discuss their clinical and public health impact and implications. Misinterpretation or true lack of abnormalities on a slide are the reasons of FN results in cytology and p16/Ki-67 dual-staining. For high-risk human papillomavirus (HPV) molecular tests, those include: truly non-HPV-associated tumors, lesions driven by low-risk HPV types, and clearance of HPV genetic material before sampling. Imprecise disease threshold definition lead to FN results in visual inspection with acetic acid. Lesions with a discrete colposcopic appearance are a source of FN in colposcopic procedures. For FAM19A4 and hsa-miR124-2 genes methylation, those may originate from borderline methylation levels. Histological misinterpretation, sampling, and laboratory errors also play a role in all types of CC screening, as well as reproducibility issue, especially in methods based on human-eye evaluation. Primary HPV-based screening combined with high quality-assured immunocytochemical and molecular triage methods seem to be an optimal approach. Colposcopy with histological evaluation remains the gold standard for diagnosis but requires quality protocols and assurance measures.

The prevalence of high/risk HPV viruses in Najaf city

Cancer is a serious public health problem, and one of the main causes of cervical cancer in women is the infection with high/risk Human papillomavirus (HPV). Human papillomaviruses are DNA viruses that have specific tropism for squamous epithelia. More than 120 different HPV types have been isolated to date; of these Low-risk HPV types, such as HPV6 and HPV11, induce benign hyperproliferations of the epithelium such as papilloma or warts. By contrast, high-risk oncogenic types (HPV16, -18, -31, -33, -35, -39, -45, - 52, - 56, - 58, - 59, - 66) are defined to have strong epidemiologic association with cervical cancer. Multiplex-PCR analysis was used for the detection and genotyping of high/risk HPV DNA in the cytological samples of cervical squamous intraepithelial lesions.The results show that the proportion of High/risk HPV genotypes in cervical smears of patients with cervical squamous intraepithelial neoplasia was 59%. In details, the genotypes were: HPV16 (15.3%), HPV18 (15.3%), HPV33 (7.7%), HPV31 (7.7%), HPV35 (30.7%), HPV56 (7.7%), HPV45 (7.7%), HPV58 (7.7%) and HPV52 (7.7%). In the other hand, none of the DNA isolated from 10 healthy group showed high/risk HPV

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

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

Recurrent fungating tumor and a chronic rash in an immunosuppressed transgender patient: a case of Buschke-Lowenstein condyloma and epidermodysplasia verruciformis.

A transgender female in her 40s with history of HIV and testicular cancer status post-genital X-irradiation presented with a perianal mass and pruritic rash across her chest. Physical examination revealed a bulky, verrucous tumor protruding outward from the anus involving the medial buttocks. Examination of the chest and arms showed numerous guttate, pink, flat-topped papules coalescing into plaques. Clinically and histologically the lesions were consistent with Buschke-Löwenstein condyloma (BLC) and acquired epidermodysplasia verruciformis (AEDV). Buschke-Löwenstein condyloma incisional biopsy tested negative for common low- and high-risk human papillomavirus (HPV) subtypes, including 6, 11, 16, and 18, possibly implicating beta HPV subtype or a less common pathogenic subtype. The patient underwent abdominoperineal resection of the BLC, which tested positive for low-risk HPV subtypes, suggesting the possibility of multiple implicated HPV subtypes in the same tumor. This case demonstrates a possible role of beta HPV or rarer HPV subtypes in the pathogenesis of verrucous carcinoma, particularly in the setting of immunosuppression.

PCR-RFLP and FTIR-based detection of high-risk human papilloma virus for cervical cancer screening and prevention

BackgroundApproximately 70% of cervical carcinoma cases show the presence of high-risk Human Papilloma Virus (HPV), especially HPV-16 and HPV-18, and can be used to stratify high risk patients from low risk and healthy. Currently, molecular biology techniques such as polymerase chain reaction (PCR) are used to identify the presence of virus in patient samples. While the methodology is highly sensitive, it is labor intensive and time-consuming. Alternative techniques, such as vibrational spectroscopy, has been suggested as a possible rapid alternative. Therefore, in this study, we evaluate the efficiency of cervical fluid Fourier Transform Infrared spectroscopy (FTIR) in patient risk stratification informed by PCR. MethodsCervical fluid samples (n = 91) were obtained from patients who have undergone routine Papanicolaou (Pap) test. Viral genome was identified and classified as high/low-risk by PCR-Restriction Fragment Length Polymorphism (PCR-RFLP). FTIR spectra were acquired from samples identified by PCR-RFLP as No-HPV (n = 10), high-risk HPV (n = 7), and low-risk HPV (n = 7). ResultsOf the 91 samples, was detected the viral genome by PCR in 36 samples. Of these 36 samples, nine samples were identified to contain high-risk HPV (HR-HPV) and nine samples were found to have low-risk HPV (LR-HPV). The FTIR spectra acquired from No-HPV, LR-HPV, and HR-HPV showed differences in 1069, 1437, 1555, 1647, 2840, 2919, and 3287 cm-1 bands. Principal Component Analysis (PCA) showed distinct clusters for No-HPV and HR-HPV and No-HPV and LR-HPV, but there was significant overlap in the clusters of HR-HPV and LR-HPV. PCA-Linear Discriminant Analysis (PC-LDA) after Leave One Out Cross Validation (LOOCV) classified No-HPV from HR-HPV and No-HPV from LR-HPV with 100% efficiency in the 1400-1800 cm-1 spectral range. LOOCV classifications for LR-HPV and HR-HPV from each other were 71 and 75%, respectively, in the 2800-3400 cm-1 spectral range. ConclusionsThe results highlight the high sensitivity of PCR-RFLP in HPV identification and show that FTIR can classify samples identified as healthy, low, and high-risk samples by PCR-RFLP. General significanceWe show the possibility of using FTIR for initial cervical cancer risk stratification followed by detailed PCR-RFLP investigations for suspect cases.

A ubiquitin variant-based affinity approach selectively identifies substrates of the ubiquitin ligase E6AP in complex with HPV-11 E6 or HPV-16 E6

The E6 protein of both mucosal high-risk human papillomaviruses (HPVs) such as HPV-16, which have been causally associated with malignant tumors, and low-risk HPVs such as HPV-11, which cause the development of benign tumors, interacts with the cellular E3 ubiquitin ligase E6-associated protein (E6AP). This indicates that both HPV types employ E6AP to organize the cellular proteome to viral needs. However, whereas several substrate proteins of the high-risk E6-E6AP complex are known, e.g. the tumor suppressor p53, potential substrates of the low-risk E6-E6AP complex remain largely elusive. Here, we report on an affinity-based enrichment approach that enables the targeted identification of potential substrate proteins of the different E6-E6AP complexes by a combination of E3-selective ubiquitination in whole-cell extracts and high-resolution MS. The basis for the selectivity of this approach is the use of a ubiquitin variant that is efficiently used by the E6-E6AP complexes for ubiquitination but not by E6AP alone. By this approach, we identified ∼190 potential substrate proteins for low-risk HPV-11 E6 and high-risk HPV-16 E6. Moreover, subsequent validation experiments in vitro and within cells with selected substrate proteins demonstrate the potential of our approach. In conclusion, our data represent a reliable repository for potential substrates of the HPV-16 and HPV-11 E6 proteins in complex with E6AP.

Microwaves can reverse the tumour phenotype of human papillomavirus type 16 (HPV16)-positive keratinocytes in 3D cell culture models: a novel therapy for HPV-associated disease?

High-risk human papillomavirus (HPV) is the causative agent of benign, precancerous and cancerous lesions, in both anogenital and oropharyngeal sites. Increased expression of the viral oncoproteins E6 and E7 are responsible for tumour progression. The treatment of these precancerous and cancerous lesions is invasive, painful and with long-term side effects. Localised microwaves have been used successfully in the clinic for the treatment of verrucas, which are caused by low-risk HPV genotypes (&gt;75% success rate versus &gt;33% for cryotherapy). Moreover, local hyperthermia is known to have anti-tumour effects. Ten-second microwave treatment of 3D in vitro-grown cervical tumour tissues (HPV16-positive SiHa cell) resulted in cell death in the treated zone while the tissue integrity was disrupted in the adjacent area. Microwaves induced apoptosis (induction of cleaved caspase 3) and autophagy (induction of LC3) and inhibited cell proliferation (loss of Ki67 and MCM2) in the entire tissue. Furthermore, HPV16 E6 and E7 expression was reduced in cells in the treated and transition zones, with subsequent induction of expression of the apoptosis-regulator, p53 over a 24 hour period following microwave treatment. Thermal stress, identified with the Heat Shock Protein 70 (HSP70) and translational stress identified by G3BP expression, was observed in the transition zone. In conclusion, we demonstrate that the microwave treatment induces cell stress pathways and inhibits HPV oncoprotein expression that causes tumour progression. Induction of apoptosis and reduced cell proliferation suggest a reversal of the cervical tumour phenotype in the 3D tissues.

HPV RNA in-situ hybridization as a diagnostic aid in papillary laryngeal lesions.

In the larynx, differentiating squamous papillomas from de-novo papillary squamous dysplasias or squamous cell carcinomas (SCC) has significant consequences for management. Overlapping clinical presentations and cytologic changes across the spectrum of papillary lesions presents diagnostic challenges for otolaryngologists and pathologists. In this study, we evaluate whether ribonucleic acid (RNA) in-situ hybridization (ISH) for low-risk and high-risk human papillomavirus (HPV) can help distinguish these lesions. We constructed tissue microarrays from 97 papillary laryngeal lesions, including 61 squamous papillomas, two papillomas with dysplasia, two SCCs-ex papilloma, 14 papillary squamous dysplasias, and 18 papillary SCCs identified at the Johns Hopkins Hospital between 2000 and 2017. We performed RNA ISH using probes for low-risk and high-risk HPV types. Low-risk HPV RNA was identified in 55 benign papillomas (90%), two papillomas with dysplasia (100%), and two SCCs-ex papilloma (100%) but was absent in de-novo papillary dysplasias and SCCs (0%). High-risk HPV RNA ISH was positive only in four papillary SCC (22%). Overall, low-risk HPV RNA ISH was 90% sensitive and 89% specific for benign papillomas with a positive predictive value of 93% and negative predictive value of 84%. In contrast, high-risk HPV was 20% sensitive for SCC. Low-risk HPV RNA ISH is a useful diagnostic adjunct for distinguishing laryngeal squamous papillomas from papillary squamous dysplasia and SCC. However, it is not entirely specific for benign processes as it is also retained in papillomas with dysplasia and SCCs-ex papilloma. Because high-risk HPV is rare in papillary laryngeal lesions, high-risk HPV RNA ISH has limited utility. Level 4 Laryngoscope, 130:955-960, 2020.

E6 proteins from high-risk HPV, low-risk HPV, and animal papillomaviruses activate the Wnt/β-catenin pathway through E6AP-dependent degradation of NHERF1.

High-risk human papillomavirus (HPV) E6 proteins associate with the cellular ubiquitin ligase E6-Associated Protein (E6AP), and then recruit both p53 and certain cellular PDZ proteins for ubiquitination and degradation by the proteasome. Low-risk HPV E6 proteins also associate with E6AP, yet fail to recruit p53 or PDZ proteins; their E6AP-dependent targets have so far been uncharacterized. We found a cellular PDZ protein called Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) is targeted for degradation by both high and low-risk HPV E6 proteins as well as E6 proteins from diverse non-primate mammalian species. NHERF1 was degraded by E6 in a manner dependent upon E6AP ubiquitin ligase activity but independent of PDZ interactions. A novel structural domain of E6, independent of the p53 recognition domain, was necessary to associate with and degrade NHERF1, and the NHERF1 EB domain was required for E6-mediated degradation. Degradation of NHERF1 by E6 activated canonical Wnt/β-catenin signaling, a key pathway that regulates cell growth and proliferation. Expression levels of NHERF1 increased with increasing cell confluency. This is the first study in which a cellular protein has been identified that is targeted for degradation by both high and low-risk HPV E6 as well as E6 proteins from diverse animal papillomaviruses. This suggests that NHERF1 plays a role in regulating squamous epithelial growth and further suggests that the interaction of E6 proteins with NHERF1 could be a common therapeutic target for multiple papillomavirus types.

The Deubiquitinase USP46 Is Essential for Proliferation and Tumor Growth of HPV-Transformed Cancers

High-risk human papilloma viruses (HPVs) cause cervical, anal, and oropharyngeal cancers, unlike the low-risk HPVs, which cause benign lesions. E6 oncoproteins from the high-risk strains are essential for cell proliferation and transformation in HPV-induced cancers. We report that a cellular deubiquitinase, USP46, is selectively recruited by the E6 of high-risk, but not low-risk, HPV to deubiqutinate and stabilize Cdt2/DTL. Stabilization of Cdt2, a component of the CRL4Cdt2 E3 ubiquitin ligase, limits the level of Set8, an epigenetic writer, and promotes cell proliferation. USP46 is essential for the proliferation of HPV-transformed cells, but not of cells without HPV. Cdt2 is elevated in human cervical cancers and knockdown of USP46 inhibits HPV-transformed tumor growth in xenografts. Recruitment of a cellular deubiquitinase to stabilize key cellular proteins is animportant activity of oncogenic E6, and the importance of E6-USP46-Cdt2-Set8 pathway in HPV-induced cancers makes USP46 a target for the therapy of such cancers.

Abstract 3417: Detection and analysis of oncovirus integration sites in FFPE-derived human tumor samples using hybrid capture and massively parallel sequencing

Abstract Viral genome integration into the host's genetic material can provide cells with selective advantages that make critical contributions to unregulated growth, cell division, and genomic instability. Current clinical tests include in situ hybridization, immunohistochemical, and real-time PCR assays that are unable to identify viral integration points in relation to oncongenic somatic mutations. This precludes a complete picture of how such mutations work together to promote, maintain, and disperse tumor progression. Precision cancer medicine employs genomic technologies (e.g., massively parallel sequencing) for high-throughput genomic profiling to molecularly define patient tumors, allowing identification of clinically actionable mutations. We created a custom probe set for targeted hybrid capture enrichment of several oncoviruses and have tested it in combination with our clinical tumor DNA profiling probe set, OncoPanel v3. Selected viruses were chosen due to their serving as causative cancer agents that disrupt tumor suppressors, facilitate genomic instability, and increase oncogene expression. The full viral genomes of hepatitis B virus and high-risk human papilloma virus (HPV) strains, 16, 18, 33, and 45 were targeted. Additionally, regions coding for E6 and E7 oncoproteins were targeted for several of the low-risk HPV strains, as was the LANA region of Kaposi's sarcoma-associated virus. FFPE-derived human tumor samples of known infection status were fragmented to 250 bp and converted into Illumina libraries. Pooled libraries underwent hybrid capture with custom, Agilent-designed OncoPanel and viral probes, and resulting captures were sequenced on an Illumina HiSeq2500 sequencer. SvABA (Structural variation and indel analysis by assembly) was used to perform de novo sequence assembly on soft-clipped and discordant aligned reads, and viral integration sites were identified by realigning contigs to the host genome to obtain breakpoint coordinates. Reduction of false positives was facilitated using dual-matched sample barcodes (IDT), which virtually eliminate barcode cross-talk, allowing for confident detection of low allele frequency events. Furthermore, inclusion of unique molecular identifiers (UMI) permitted discrimination of PCR duplicates and errors. Our results demonstrate high concordance with clinical samples of known infection status and provide viral integration break point locations in association with genomic tumor mutations. Viral integration sites are often associated with deletions or amplifications of the host's flanking genomic regions. Furthermore, viral integration may disrupt or enhance expression of tumor suppressors and oncogenes, respectively. Coupled with tumor molecular profiling, this information will better inform patient treatment. Citation Format: Michael K. Slevin, Winslow T. Powers, Robert T. Burns, Bruce M. Wollison, Haley A. Coleman, Amanda L. Paskavitz, Anwesha Nag, Danielle K. Manning, Elizabeth Garcia, Matthew D. Ducar, Aaron R. Thorner, Laura E. MacConaill. Detection and analysis of oncovirus integration sites in FFPE-derived human tumor samples using hybrid capture and massively parallel sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3417.

HPV Vaccination: Prevention of Cervical Cancer in Serbia and in Europe

Summary The identification of the high-risk human papilloma viruses (HPVs) as a cause of cervical cancer offered the possibility for the development of a HPV vaccine. Twenty years after this identification of the HPV types, the first HPV vaccine came to the market. There are three HPV vaccines today on the market, all containing the virus-like particles (VLPs) of the HPV types 16 and 18, which are considered to cause 77 % of all cancers caused by HPVs. In addition, two of the vaccines contain two low-risk HPV types (6 and 11)-quadrivalent or the same as low-risk types and additional high-risk HPV types (31, 32, 45, 52, 58)-nonavalent vaccines. The cervical cancer protection efficacy of the vaccines is very high, around 100%. The VLPs of the 6- and 11-type offer efficient protection against genital warts. Unfortunately, the implementation of the vaccination is actually not so high despite all scientific and medical facts, but their rates in Europe are steadily increasing reaching about 90% in one country after another. In Serbia, all of the three vaccines are on the market but are highly underused. Actually, there is no national program and the Serbian vaccination rates are very low. High vaccination rates in Serbia need to be achieved as a goal of prevention of cervical cancer.

Interferon lambda4 polymorphism is not associated with human papillomavirus infection outcome.

Interferon (IFN) lambdas are important specific components of the mucosal innate immune response. The IFN lambda 4 (IFNL4) dinucleotide polymorphism (ΔG/TT) determines the IFN lambdas and related Interferon-stimulated genes activation, in HCV and other chronic infections. Our group first reported that IFN Lambda response was impaired in high-risk Human Papillomavirus (HPV) cervical infections and in precancerous lesions. Accordingly, we sought to evaluate the possible role of the IFNL4 polymorphism in determining HPV infection outcome. The ΔG/TT alleles were not differently distributed in 221 women with high- or low-risk HPV infection, with HPV infection clearance or persistence, and with abnormal cytology.

High rates of bacterial vaginosis and Chlamydia in a low-income, high-population-density community in Cape Town

Young South African women, from resource-poor communities, face several sexual and reproductive health challenges. Here we describe the vaginal microbiota and sexually transmitted infection (STI) prevalence of 102; 16–22-year-old, HIV-negative South African women from a low-income, high-population-density community in Cape Town (CPT). Vaginal microbiota were profiled using 16S rRNA amplicon sequencing; bacterial vaginosis (BV) status was established using Nugent scoring and STIs were determined by multiplex polymerase chain reaction. STIs were common, with 55% of women having at least one STI; 41% were infected with high-risk human papilloma virus (HPV) and a further 28% with low-risk HPV; 44% were infected with Chlamydia, 16% of whom had at least one additional STI. Similarly, BV rates were very high, with 55% of women classified as BV-positive (Nugent score ≥7), 7% as BV-intermediate (Nugent score 3–6) and 38% as BV-negative (Nugent 0–2). Group B Streptococcus (Streptococcus agalactiae), the leading cause of neonatal sepsis, was present in 25% of BV-positive women and 28% of BV-negative women, and was significantly more abundant among BV-negative women. Both Chlamydia infection and BV may adversely affect reproductive health and place these women at additional risk for HIV acquisition. The high abundance of Prevotella amnii, in particular, may increase HIV risk, given its inflammatory capacity. Laboratory-based testing for STIs (Chlamydia and Gonorrhoeae in particular) appear to be warranted in this community, together with further monitoring or treatment of BV.Research correlation: This article is the original version, of which an Afrikaans translation was made available to provide access to a larger readership, available here: https://doi.org/10.4102/satnt.v36i1.1495

Abstract 5341: HPV16 E6 oncoprotein modulates the DPPIV/CD26 in primary keratinocytes

Abstract Cervical cancer is related to the persistent infection by high-risk human papillomavirus (HPV) subtypes, such as types 16 and 18. The E6 and E7 oncoproteins significantly contribute to the carcinogenic potential of high-risk HPV, through the degradation of p53 and pRb, respectively. The exoprotease dipeptidyl peptidase IV (DPPIV) also known as CD26, is a multifunctional protein involved in several processes related to cancer. DPPIV/CD26 has an intrinsic peptidase activity, able to degrade some bioactive peptides and chemokines, thereby regulating cell migration, proliferation and survival. It has been reported that the reduction in DPPIV/CD26 expression is associated with tumor progression in different types of cancer. Moreover, studies in cervical cancer samples and cell lines point to a reduction in the expression of this protein. However, there are no studies addressing the relationship between HPV infection and DPPIV/CD26 expression. We analyzed the influence of HPV oncoproteins on DPPIV/CD26 expression in human keratinocyte transduced with E6, E7 and E6E7. We observed that HPV16 E6 expression is associated to a reduction in DPPIV/CD26 expression at mRNA and protein levels, whereas HPV16 E7 does not affect DPPIV/CD26 expression. HPV16 E6E7 co-expression leads to a reduction in DPPIV/CD26 expression similar to that found in E6 transduced cells. In addition, we note a more pronounced reduction in DPPIV/CD26 expression in immortalized cells expressing E6E7. Furthermore, keratinocytes expressing HPV16 E6 mutant sequence and HPV11 E6, that do not bind to E6AP and do not degrade p53, have no effect on DPPIV/CD26 expression. Our results suggest that the HPV16 E6 oncoprotein can downregulates DPPIV/CD26. In addition, preliminary results suggest that modulation of DPPIV/CD6 mediated by E6 can be dependent on degradation of p53, since HPV16 E6 mutant and low-risk HPV E6 were not able to affect CD26 expression. Furthermore, the process of cell immortalization also appears to be related to the reduction of DPPIV/CD26 expression. Therefore, these results indicate that HPV oncoproteins promote imbalance DPPIV/CD26 expression which may be relate to cervical carcinogenesis. Citation Format: Aline Beckenkamp, Bruna Prati, Silvya Stuchi Maria-Engler, Guido Lenz, Diogo André Pilger, Enrique Mario Pierulivo, Andréia Buffon. HPV16 E6 oncoprotein modulates the DPPIV/CD26 in primary keratinocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5341. doi:10.1158/1538-7445.AM2017-5341

Characteristics and Distribution of Penile Lesions in Croatian Men with Laboratory-Confirmed Low-Risk and High-Risk Human Papillomavirus (HPV) Infection.

Studies that compare penoscopic evaluation with the results of molecular human papillomavirus (HPV) testing are scarce. This study assessed and compared both type and distribution of various penile lesions using penoscopy (peniscopy) technique in Croatian men with different, laboratory-confirmed HPV status. From a large cohort of men attending an outpatient STD clinic for HPV testing, a total of 120 patients were randomly selected and grouped into those positive for low-risk HPV, high-risk HPV, both low-risk and highrisk HPV, and those with negative results. Samples for HPV-DNA detection were taken by penile brushing and tested with the hc2 HPV DNA Test using Hybrid Capture 2 technology. Lesions were observed by photocolposcope after the application of aqueous 5% acetic acid, and classified as flat (macular), papular, papillary, classical condyloma, PIN-suspicious and non-specific lesions. The results have shown that flat and non-specific acetowhite lesions were the most common overall. All groups differed significantly with respect to papular and papillary lesions. A combination of heterogeneous lesions (i.e., a mixed penoscopic pattern) was commonly observed in all HPV-positive groups, but was significantly lower in the HPV-negative group. A majority of lesions were located in the coronal sulcus, and the four groups differed with respect to the location only considering the lesions of the penile shaft. Distribution of lesions in different sites did not appear to be significantly different with respect to the group, although differences within the high-risk HPV group and the group with both low-risk and high-risk HPV were detected. Penoscopy is relevant, but not a conclusive diagnostic tool for differentiating HPV from non-HPV findings in men - thus combining it with an HPV DNA test represents a more reliable approach.