Oncogenic Potential Of Human Papillomavirus Research Articles

Knowledge and attitudes regarding sexually transmitted infections among healthcare workers.

Healthcare workers have a fundamental role in providing care and education on sexually transmitted infections (STIs). However, their knowledge is often worryingly limited. This study aimed to assess the real knowledge and attitude regarding STIs among healthcare workers of the IRCCS Ospedale Policlinico San Martino, Genoa, Italy. The recruited subjects were asked to complete a 31-item questionnaire, divided into 3 sections: socio-demographic context, knowledge about STIs, and personal sexual behavior. We enrolled 140 subjects, employed as nurses (52.9%), physicians (12.9%), laboratory technicians (7.1%), or other workers (27.1%). Despite the generalized erroneous belief of having a good level of knowledge on the matter, only one-third of the subjects could correctly identify STIs among a list of diseases, and less than one-third correctly recognize all possible ways of transmission. Human immunodeficiency virus (HIV) was the most frequently recognized STI (97%), but only 39.2% of healthcare workers were correctly informed about the body fluids that can transmit the virus. Most participants (93.5%) correctly identified condoms as effective in preventing STIs but did not indicate complete abstinence as the only way to guarantee protection against STIs. Most participants were informed on the oncogenic potential of human papillomavirus (HPV) infections (82%), the usefulness of the Pap test (85.7%), and the existence of vaccines against some STIs (63.5%). Overall, healthcare workers have limited knowledge about STIs. Creating specific educational programs aimed at healthcare providers should become a priority.

The Oncogenic Potential of Human Papillomavirus in Relation to Multiple Types of Cancer in Saudi Arabia: A Systematic Review.

The oncogenic potential of human papillomavirus (HPV) has been widely acknowledged in relation to multiple types of cancer. The objective of this investigation was to conduct a comprehensive assessment of the available evidence pertaining to the correlation between HPV and various types of cancer, such as cervical, colon, ovarian, and head and neck cancers, in the Kingdom of Saudi Arabia (KSA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were complied with to conduct a systematic literature search aimed at identifying studies that explore the correlation between HPV and the specified cancers. Databases such as Web of Science, Embase, PubMed, and the Cochrane Library were queried up until May of 2023. Relevant literature was obtained, information was extracted, and the methodological rigor was evaluated. The high-risk HPV, namely HPV-16 and HPV-18, were detected as the most prevalent variants in KSA. A significant proportion of cervical cancer cases in the region were found to be associated HPV infection. The molecular tests have furnished evidence that establishes a connection between HPV infection and colonic polyps as well as colorectal cancer. This finding suggests that HPV may have a plausible role in the etiology of these medical conditions. The results of genotyping and integration analyses suggest a probable correlation between HPV and the development of ovarian cancer. Additionally, the prevalence of head and neck squamous cell cancer related to HPV was notably reduced in this particular geographical area. This study presents persuasive findings that establish a connection between HPV and cervical cancer and proposes plausible correlations with squamous cell carcinomas in the colon, ovaries, and head and neck. The aforementioned results emphasize the necessity for additional inquiry into the function of HPV in the onset and advancement of said malignancies. Further investigations are necessary to augment our comprehension of the role of HPV in these neoplasms.

Deployment and assessment of a deep learning model for real-time detection of anal precancer with high frame rate high-resolution microendoscopy

Anal cancer incidence is significantly higher in people living with HIV as HIV increases the oncogenic potential of human papillomavirus. The incidence of anal cancer in the United States has recently increased, with diagnosis and treatment hampered by high loss-to-follow-up rates. Novel methods for the automated, real-time diagnosis of AIN 2+ could enable "see and treat" strategies, reducing loss-to-follow-up rates. A previous retrospective study demonstrated that the accuracy of a high-resolution microendoscope (HRME) coupled with a deep learning model was comparable to expert clinical impression for diagnosis of AIN 2+ (sensitivity 0.92 [P = 0.68] and specificity 0.60 [P = 0.48]). However, motion artifacts and noise led to many images failing quality control (17%). Here, we present a high frame rate HRME (HF-HRME) with improved image quality, deployed in the clinic alongside a deep learning model and evaluated prospectively for detection of AIN 2+ in real-time. The HF-HRME reduced the fraction of images failing quality control to 4.6% by employing a high frame rate camera that enhances contrast and limits motion artifacts. The HF-HRME outperformed the previous HRME (P < 0.001) and clinical impression (P < 0.0001) in the detection of histopathologically confirmed AIN 2+ with a sensitivity of 0.91 and specificity of 0.87.

Preferential Tissue Sites of Different Cancer-Risk Groups of Human Papillomaviruses.

The oncogenic potential of human papillomavirus (HPV) may be used to determine the tissue tropism of each HPV type. Cervical cancer develops in the squamo-columar junction of the cervices, and most lesions are induced by high-risk (HR) HPV types. This suggests that HR types preferentially infect the cervix, whereas the preferential infection site for low-risk (LR) types is not well defined. The determination of HPV tropism when using cytology samples can be uncertain since it is difficult to avoid contamination of cell samples between the cervix and the vagina. Herein, cell samples were carefully collected by independently scraping the cervix and vagina, after which the HPV types were determined. HPV tissue tropism was determined by considering what HPV types were positive at only one of the sites (the cervix or the vagina) as the viruses that preferentially infected that site. This method revealed that all LR types were only identified in vaginal samples, whereas 87% of HR types were identified in cervical sites. Thus, LR types may preferentially infect the vagina, whereas HR types infect the cervix. These findings suggest that preferential tissue tropism of certain HPV types is a probable factor for malignant progression.

Awareness of Human Papillomavirus and Its Oncogenic Potential in Head and Neck Cancer among Students: Still More Questions than Answers.

In the past years, human papilloma virus (HPV) has been proved to be an important risk factor for head and neck squamous cell carcinomas (HNSCCs), especially in the oropharynx (OPCCS). The aim of this study was to assess the level of knowledge about HPV among students and to raise their awareness on the issue. A 22-question questionnaire was uploaded to an online service. Information about the project was sent out to students from three Universities in Lodz, Poland. All data were collected via questionnaire website tools. A total of 1710 students participated in this study. The group was divided into medical (MS) and non-medical (non-MS) students. Merely 59.38% of the non-MS had ever heard about HPV. Only 44.74% of the non-MS knew about vaccines against HPV. The oncogenic potential of HPV was evident for 81.17% of the MS and only 55.92% of the non-MS. Very similar numbers of respondents from both groups (39.21% vs. 36.47%) knew that HPV may cause cancers other than cervical. Nearly half of the respondents from both groups (46.28% vs. 48.32%) did not know about the risk of developing oral or oropharyngeal cancer. The level of knowledge about the consequences of HPV infection in head and neck cancers in young adults remains insufficient.

Association between human papillomavirus (HPV) and oesophageal squamous cell carcinoma: a meta-analysis

The oncogenic potential of human papillomaviruses (HPV) is well known in the context of cervical carcinoma; however, their role in the development of oesophageal squamous cell carcinoma (OSCC) is less clear. We aimed to determine the extent of the association between HPV infection and OSCC. A comprehensive literature search found 132 studies addressing HPV and OSCC in human cases, and a meta-analysis was performed using a random-effects model. There was evidence of an increased risk of OSCC in patients with HPV infection [odds ratio (OR) 2·69, 95% confidence interval (CI) 2·05-3·54]. The prevalence of HPV in OSCC was found to be 24·8%. There was an increased risk associated with HPV-16 infection (OR 2·35, 95% CI 1·73-3·19). Subgroup analyses showed geographical variance, with Asia (OR 2·94, 95% CI 2·16-4·00), and particularly China (OR 2·85, 95% CI 2·05-3·96) being high-risk areas. Our results confirm an increase in HPV infection in OSCC cases.

Comparative analysis of virus–host interactomes with a mammalian high-throughput protein complementation assay based on Gaussia princeps luciferase

Comparative interactomics is a strategy for inferring potential interactions among orthologous proteins or “interologs”. Herein we focus, in contrast to standard homology-based inference, on the divergence of protein interaction profiles among closely related organisms, showing that the approach can correlate specific traits to phenotypic differences. As a model, this new comparative interactomic approach was applied at a large scale to human papillomaviruses (HPVs) proteins. The oncogenic potential of HPVs is mainly determined by the E6 and E7 early proteins. We have mapped and overlapped the virus–host protein interaction networks of E6 and E7 proteins from 11 distinct HPV genotypes, selected for their different tropisms and pathologies. We generated robust and comprehensive datasets by combining two orthogonal protein interaction assays: yeast two-hybrid (Y2H), and our recently described “high-throughput Gaussia princeps protein complementation assay” (HT-GPCA). HT-GPCA detects protein interaction by measuring the interaction-mediated reconstitution of activity of a split G. princeps luciferase. Hierarchical clustering of interaction profiles recapitulated HPV phylogeny and was used to correlate specific virus–host interaction profiles with pathological traits, reflecting the distinct carcinogenic potentials of different HPVs. This comparative interactomics constitutes a reliable and powerful strategy to decipher molecular relationships in virtually any combination of microorganism–host interactions.

Development of a Bead-Based Multiplex Genotyping Method for Diagnostic Characterization of HPV Infection

The accurate genotyping of human papillomavirus (HPV) is clinically important because the oncogenic potential of HPV is dependent on specific genotypes. Here, we described the development of a bead-based multiplex HPV genotyping (MPG) method which is able to detect 20 types of HPV (15 high-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68 and 5 low-risk HPV types 6, 11, 40, 55, 70) and evaluated its accuracy with sequencing. A total of 890 clinical samples were studied. Among these samples, 484 were HPV positive and 406 were HPV negative by consensus primer (PGMY09/11) directed PCR. The genotyping of 484 HPV positive samples was carried out by the bead-based MPG method. The accuracy was 93.5% (95% CI, 91.0–96.0), 80.1% (95% CI, 72.3–87.9) for single and multiple infections, respectively, while a complete type mismatch was observed only in one sample. The MPG method indiscriminately detected dysplasia of several cytological grades including 71.8% (95% CI, 61.5–82.3) of ASCUS (atypical squamous cells of undetermined significance) and more specific for high grade lesions. For women with HSIL (high grade squamous intraepithelial lesion) and SCC diagnosis, 32 women showed a PPV (positive predictive value) of 77.3% (95% CI, 64.8–89.8). Among women >40 years of age, 22 women with histological cervical cancer lesions showed a PPV of 88% (95% CI, 75.3–100). Of the highest risk HPV types including HPV-16, 18 and 31 positive women of the same age groups, 34 women with histological cervical cancer lesions showed a PPV of 77.3% (95% CI, 65.0–89.6). Taken together, the bead-based MPG method could successfully detect high-grade lesions and high-risk HPV types with a high degree of accuracy in clinical samples.

Oncogenic potential of Human Papillomavirus (HPV) and its relation with cervical cancer.

Human Papillomavirus (HPV) is the most common cause of cervical cancer. Cervical cancer being the second most common cancer after lung cancer, affecting women of different age groups; has a prevalence of about 20% in young sexually active women. Among different types of HPV, HPV16 the major strain causing this cancer and is sexually transmitted had been unnoticed for decades. Keeping in mind the multiple risk factors related with cervical cancer such as early age sexual activities, teenage pregnancies, smoking, use of oral contraceptives, having multiple sex partners, hormone replacement therapies and various other unknown factors lead to the onset of the disease. Awareness for various diagnostic procedures such as Pap smears screening prove to be an effective way in eradicating the oncogenic potential of HPV.

Epidermodysplasia verruciformis: a model for understanding the oncogenicity of human papillomaviruses.

The first evidence for the oncogenic potential of human papillomaviruses (HPVs) was obtained through the study of epidermodysplasia verruciformis (EV). This rare skin disease is characterized by disseminated, refractor, pityriasis versicolor-like lesions as well as flat wart-like lesions, and by the development of skin carcinomas in about 30% of the patients. EV is a multifactorial disease involving genetic, immunological and extrinsic (actinic) factors, in addition to infection with specific HPV types. A number of HPVs (at least 15 types) have been characterized in benign EV lesions. HPV DNA sequences are regularly detected in EV carcinomas but, in contrast to benign lesions, the types associated with cancers are usually restricted to HPV-5 and, less frequently, HPV-8, an HPV-5-related type. HPV-5 genomes are usually found as free monomeric or oligomeric DNA molecules in EV carcinomas, and frequently contain deletions. This is in contrast with HPV DNA sequences in genital cancers, which are often integrated into the host DNA. Evidence for the transcription of HPV-5 genomes in primary and metastatic EV carcinomas has recently been obtained. The available data indicate that HPV-5 and some HPV-5-related types have an oncogenic potential and play a role in the malignant transformation of EV lesions. Infection by these HPVs must be considered a major risk factor for the development of cancers in EV patients. EV HPV DNA sequences have only rarely been detected in premalignant or malignant lesions of the skin in the general population. This further stresses the role of genetic, immunological and extrinsic factors in the abnormal susceptibility of EV patients to a set of specific HPV types.

The oncogenic potential of human papillomaviruses: a review on the role of host genetics and environmental cofactors

Human papillomaviruses (HPVs), with over 100 genotypes, are a very complex group of human pathogenic viruses. In most cases, HPV infection results in benign epithelial proliferations (verrucae). However, oncogenic types of HPV may induce malignant transformation in the presence of cofactors. For example, over 99% of all cervical cancers and a majority of vulval, vaginal, anal and penile cancers are the result of oncogenic HPV types. Such HPV types have been increasingly linked to other epithelial cancers involving the skin, larynx and oesophagus. Although viral infection is necessary for neoplastic transformation, evidence suggests that host and environmental cofactors are also required. Research investigating HPV oncogenesis is complex and quite extensive. The inability to produce mature HPV virions in animal models has been a major limitation in fully elucidating the oncogenic potential and role of associated cofactors in promoting malignant transformation in HPV-infected cells. We have reviewed the literature and provide a brief account of the current understanding of HPV oncogenesis, emphasizing the role of genetic susceptibility, immune response, and environmental and infectious cofactors.

Moderate variation of the oncogenic potential among high-risk human papillomavirus types in gynecologic patients with cervical abnormalities.

The oncogenic potential of human papillomavirus (HPV) infection was assessed by following the disease course in 455 patients who had had a routine diagnostic Hybrid Capture HPV test due to squamous cell abnormalities of the uterine cervix as detected by cytology and/or colposcopy. At entry, 308 patients had cytologic atypia classified as P3 by the Papanicolau classification, 168 had a positive high-risk HPV test, and 23 were infected only with low-risk HPV. The patients were followed-up using the patient registry until the endpoint of histologically diagnosed cervical intraepithelial neoplasia (CIN). High-grade CIN was diagnosed in 75 surgical biopsies. High-risk HPV infection (relative risk: 76.8 CI(95): 23.7-249.5), cytologic atypia (RR: 16.2 CI(95): 3.9-66.6), and age above 35 (RR: 1.99 CI(95): 1.26-3.16) were independent risk factors for high-grade CIN, while the viral load did not predict oncogenic progression (P = 0.47). After PCR-RFLP typing, the high-risk types were classified into groups as follows: (1) types 16 and 18, (2) types 45, 52, and 56, (3) types 31, 33, 35, 51, and 58. The relative risks of high-grade CIN were 119.1 (CI(95): 36.2-390.9) for group 1, 44.4 (CI(95): 9.8-201) for group 2, and 39.7 (CI(95): 10.9-144.8) for group 3, respectively. The risk ratios between the groups of high-risk types were found to differ at most by a factor of 2.98 (corrected P value: 0.007) indicating that the oncogenic potential varies moderately within the high-risk group of HPVs.

Human papillomavirus and p53 mutational status as prognostic factors in head and neck carcinoma.

Mutations of the p53 tumor-suppressor gene are common in squamous cell carcinoma of the head and neck (SCCHN) and may portend a worse prognosis. Human papillomavirus (HPV) represents another potential prognostic factor for SCCHN. The oncogenic potential of HPV may be due to the ability of its E6 oncoprotein to promote degradation of wild-type p53 protein. We wish to determine whether there is a lower incidence of p53 mutations in HPV-positive versus HPV-negative tumors, and if HPV and/or p53 status has an impact on survival. Thirty-two SCCHN specimens were analyzed for mutations of the p53 gene using single-strand conformational polymorphism (SSCP) analysis followed by DNA sequencing. The HPV status of all specimens was evaluated by use of polymerase chain reaction with HPV consensus primers and Southern blot hybridization. Pertinent clinical information was obtained from chart review. Nonsilent p53 mutations were present in 2 of 15 (13%) of HPV-positive tumors compared with 6 of 17 (35%) of HPV-negative tumors (p =.229; Fisher's exact test, odds ratio.28). A survival advantage was found between HPV-positive compared with HPV-negative specimens (p =.0264) and between p53 wild type compared with p53 mutant specimens (p =.01) by univariate log rank analysis. When stratified according to both HPV and p53 status, a statistically significant survival difference was observed largely because of a 100% survival for the HPV-positive/p53 wild-type group (p =.003). This preliminary study supports the notion that the presence of HPV confers a survival advantage among HNSCC patients, particularly when p53 is wild type.

Up-regulation of p53 by antisense expression of HPV18 E6 oncogene does not influence the level of MN/CA IX tumor-associated protein in HeLa cervical carcinoma cells.

Oncogenic potential of human papillomaviruses is related to capacity of HPV-encoded oncoproteins to bind and inactivate tumor suppressor proteins. Interaction of p53 with HPV E6 results in aberrant regulation of various cellular genes. We evaluated the possible involvement of MN/CA9 gene, whose expression is closely associated with cervical carcinomas, in regulatory pathways driven by p53 and E6. We demonstrated that one of the two p53 consensus sequences present in MN/CA9 promoter participates in DNA-protein interaction but it does not bind p53. Tetracycline-inducible antisense expression of HPV18 E6 in human cervical carcinoma HeLa cells resulted in increased level of p53 but did not affect expression of MN/CA IX protein. Therefore we conclude that at least in HeLa cells there is no direct relationship between expression of MN/CA IX and expression of E6 or p53.

The role of human papillomavirus in carcinoma

Human papillomaviruses have long been identified as the cause of common warts and condylomata acuminata. Evidence is now accumulating that human papillomaviruses may be involved in not only benign, but also in malignant neoplasms. They might also be significant in the malignant transformation of cutaneous neoplasms. This review examines the oncogenic potential of human papillomaviruses when they are found in carcinomas in various anatomic areas, including the skin.

Prevalence of Human Papillomavirus Genomes in Tissues from the Lower Genital Tract as Detected by Molecular In Situ Hybridization

Incidence cases of human papillomavirus (HPV)-related disease of the lower anogenital tract were prospectively collected and submitted to RNA-DNA in situ hybridization, which allows a direct correlation between morphology and the presence of viral DNA. The overall HPV detection rate in condylomata and intraepithelial or invasive neoplasia varied for the different genital areas: cervix (64%), vagina (56%), vestibule (59%), vulva (50%), and penis (42%). HPVs 6/11 were associated with condylomata, whereas HPV 16 was associated with intraepithelial and invasive neoplasia. Not a single case of intraepithelial or invasive neoplasia contained HPV 6/11, which supports the notion of the oncogenic potential of HPV 16. Condylomata were positive for HPV 16 only when adjacent to HPV 16-positive cervical intraepithelial neoplasias (CINs). The amount of viral DNA (copy number) was low in invasive cancers, intermediate in intraepithelial neoplasia, and conspicuously high in condylomata. In biopsies (n = 142) taken from lesions suggestive of subclinical papillomavirus infection on the basis of minor colposcopic and histologic abnormalities, HPV DNA was not detectable. Histologically normal tissue (n = 210) adjacent to condyloma, CIN, or cancer, and thus potential carrier of latent HPV infection, also proved negative for HPV DNA by in situ hybridization. The inability to detect viral DNA by in situ hybridization in tissues diagnosed as subclinically or latently infected may have been due to limited sensitivity of the hybridization method applied in this study.

Human papillomaviruses biochemical and biologic properties

The viral origin of warts and condylomas was established at the beginning of this century by experiments on the transmission of warts by means of cell-free tissue extracts. 1 For a long time, a single virus—the human wart virus—was considered responsible for these lesions, 1 although the multiplicity of human papillomaviruses (HPVs) was suspected on the basis of epidemiologic, 2 serologie, 3 and histologic 4,5 data. It was, thus, generally thought that “the clinical type is determined by the local conditions at the site of infection and not by the virus” 1 and that the clinical evolution of the lesions—in particular, the rare malignant transformation 6,7 of genital condylomas and that of the cutaneous lesions of patients suffering from epidermodysplasia verruciformis (EV)—depended on immunologic, genetic, or extrinsic factors. 1,6,8 The characterization of HPVs and the study of their pathogenic properties have long been hindered by the absence of a cellular system permitting the in vitro replication of these viruses. 9 During the last few years, new methods of analysis of the viral DNA—in particular, the molecular cloning of viral genomes in a plasmid or in the DNA of a bacteriophage—have permitted considerable improvement in our knowledge of HPVs. 10–12 At least 28 HPV types now are recognized 13–29 (Ostrow, R. personal communication). It seems likely that the different clinical types of lesions classically associated with an HPV are, in fact, distinct diseases caused by specific viruses. 23,30–34 Finally, the discovery of the high frequency of infection of the uterine cervix by an HPV, 36,36 as well as the frequent detection of HPV DNA sequences in neoplasias of the skin, 16,32,37–39 the external genitalia, 40–46 and the uterine cervix 24,25 have broadened the spectrum of the pathogenicity of PVs for human beings and imposed the idea that infection by specific HPV types is a risk factor for the development of these neoplasias. After reviewing the physicochemical and biologic characteristics of HPVs and the methods used for their study, we will present recent data on the nomenclature, the pathogenicity, and the oncogenic potential of HPVs.

Human papillomavirus in various lesions of the head and neck.

The association of human papillomavirus with benign and malignant epithelial lesions of the head and neck has been studied by a peroxidase-antiperoxidase technique having immunospecificity against genus-specific structural antigens of the papillomaviruses. More than 360 specimen blocks from 144 patients were evaluated. There was evidence of human papillomavirus antigen in three out of eight patients with childhood-onset laryngeal papillomas (37.5%) and in four out of eight patients with adult-onset papillomas (50%). A patient with an unusual flat, wartlike lesion appearing as an oral cavity leukoplakia had detectable papillomavirus antigen in it. None of the 13 cases of inverting papilloma or any of the malignant lesions studied showed evidence for the presence of papillomavirus antigen. There is currently only suggestive evidence for the oncogenic potential of human papillomavirus in the head and neck.