Alpha Human Papillomavirus Types Research Articles

Alpha Human Papillomavirus Types and Genotype Distribution in Psoriasis Patients: A Cross-Sectional Regional Study in Turkey

Background: Human papillomaviruses (HPVs) are members of the Papillomaviridae family, characterized by circular, double-stranded DNA. They exhibit strict tropism, infecting either mucosa or skin. The role of HPV in the etiology of psoriasis remains unclear. Objectives: The aim of this study was to determine the presence of alpha human papillomavirus in the skin scrapings of patients with psoriasis and its genotype distributions. Methods: The study employed a cross-sectional design and included 53 psoriasis patients and 47 healthy controls from December 2020 to May 2021. After DNA isolation from skin scrapings, the L1 gene region of HPV was amplified using MY09/11 and GP5 +/6 + consensus primer sequences. The HPV genotypes were determined through direct DNA sequence analysis of polymerase chain reaction (PCR) products. Results: HPV DNA was detected in 34% of psoriasis patients and 29.8% of healthy individuals. Among the patients, HPV18 was found in 11.1%, HPV31 in 38.9%, and HPV81 in 50%. In the healthy individuals, HPV31 was found in 7.1% and HPV81 in 92.9%. HPV DNA was detected in 31.8% of patients who received psoralen UV-A (PUVA) treatment and 35.5% of those who did not. High-risk (HR) HPV18 was identified in two patients (28.6%) within the group treated with PUVA. Conclusions: There is a potential risk for psoriasis patients who receive lifelong immunosuppressive treatment in the case of persistent infections with the HR oncogenic types (HPV18 and HPV31) of alpha HPVs identified in this study. The high prevalence of low-risk HPV81 in healthy individuals suggests that alpha HPVs might occur as members of the normal skin flora without causing cutaneous lesions in healthy skin.

The Role of Beta HPV Types and HPV-Associated Inflammatory Processes in Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is a common form of skin cancer with a complex but not fully understood pathogenesis. Recent research suggests the role of beta human papillomavirus (HPV) types and HPV-associated inflammatory processes in cSCC development. Beta HPV types are components of the normal flora; however, under the influence of certain cofactors, the virus may trigger a malignant process. Dysregulation of the immune system (chronic inflammation and immunosuppression), environmental factors (ultraviolet radiation), and genetic factors are the most important cofactors involved in beta HPV-related carcinogenesis. In addition, the oncoproteins E6 and E7 of beta HPV types differ biochemically from their counterparts in the structure of alpha HPV types, resulting in different mechanisms of action in carcinogenesis. The aim of our manuscript is to present an updated point of view on the involvement of beta HPV types in cSCC pathogenesis.

HPV Oncoproteins and the Ubiquitin Proteasome System: A Signature of Malignancy?

Human papillomavirus (HPV) E6 and E7 oncoproteins are critical for development and maintenance of the malignant phenotype in HPV-induced cancers. These two viral oncoproteins interfere with a plethora of cellular pathways, including the regulation of cell cycle and the control of apoptosis, which are critical in maintaining normal cellular functions. E6 and E7 bind directly with certain components of the Ubiquitin Proteasome System (UPS), enabling them to manipulate a number of important cellular pathways. These activities are the means by which HPV establishes an environment supporting the normal viral life cycle, however in some instances they can also lead to the development of malignancy. In this review, we have discussed how E6 and E7 oncoproteins from alpha and beta HPV types interact with the components of the UPS, and how this interplay contributes to the development of cancer.

Roles of Fc Domain and Exudation in L2 Antibody-Mediated Protection against Human Papillomavirus.

To address how L2-specific antibodies prevent human papillomavirus (HPV) infection of the genital tract, we generated neutralizing monoclonal antibodies (MAbs) WW1, a rat IgG2a that binds L2 residues 17 to 36 (like mouse MAb RG1), and JWW3, a mouse IgG2b derivative of Mab24 specific for L2 residues 58 to 64. By Western blotting, WW1 recognized L2 of 29/34 HPV genotypes tested, compared to only 13/34 for RG1 and 25/34 for JWW3. WW1 IgG and F(ab')2 bound HPV16 pseudovirions similarly; however, whole IgG provided better protection against HPV vaginal challenge. Passive transfer of WW1 IgG was similarly protective in wild-type and neonatal Fc receptor (FcRn)-deficient mice, suggesting that protection by WW1 IgG is not mediated by FcRn-dependent transcytosis. Rather, local epithelial disruption, required for genital infection and induced by either brushing or nonoxynol-9 treatment, released serum IgG in the genital tract, suggesting Fc-independent exudation. Depletion of neutrophils and macrophages reduced protection of mice upon passive transfer of whole WW1 or JWW3 IgGs. Similarly, IgG-mediated protection by L2 MAbs WW1, JWW3, and RG1 was reduced in Fc receptor knockout compared to wild-type mice. However, levels of in vitro neutralization by WW1 IgG were similar in TRIM21 knockout and wild-type cells, indicating that Fc does not contribute to antibody-dependent intracellular neutralization (ADIN). In conclusion, the Fc domain of L2-specific IgGs is not active for ADIN, but it opsonizes bound extracellular pseudovirions for phagocytes in protecting mice from intravaginal HPV challenge. Systemically administered neutralizing IgG can access the site of infection in an abrasion via exudation without the need for FcRn-mediated transcytosis.IMPORTANCE At least 15 alpha HPV types are causative agents for 5% of all cancers worldwide, and beta types have been implicated in nonmelanoma skin cancer, whereas others produce benign papillomas, such as genital warts, associated with considerable morbidity and health systems costs. Vaccines targeting the minor capsid protein L2 have the potential to provide broad-spectrum immunity against medically relevant HPVs of divergent genera via the induction of broadly cross-neutralizing serum IgG. Here we examine the mechanisms by which L2-specific serum IgG reaches the viral inoculum in the genital tract to effect protection. Abrasion of the vaginal epithelium allows the virus to access and infect basal keratinocytes, and our findings suggest that this also permits the local exudation of neutralizing IgG and vaccine-induced sterilizing immunity. We also demonstrate the importance of Fc-mediated phagocytosis of L2 antibody-virion complexes for humoral immunity, a protective mechanism that is not detected by current in vitro neutralization assays.

Prevalence and Transmission of Beta and Gamma Human Papillomavirus in Heterosexual Couples.

BackgroundBeta (β) and gamma (γ) human papillomavirus (HPV) are commonly found on the skin. Few of the β types are associated with nonmelanoma skin cancer. Little is known about transmission patterns of these HPV, specifically in the anogenital (AG) areas. The primary objective of this study was to examine the AG concordance and transmission of β and γHPV types between heterosexual couples.MethodsArchival samples from a previously published study examining concordance of alpha HPV types between couples were tested for β and γHPV. Hand, mouth, and genital samples were obtained 5 times over a 6-week period.ResultsOf the 21 couples examined, β and γHPV were detected in AG sites in 67% and 30% of men, respectively, and 41% and 25% of women. Positive concordance for β and γHPV was 27% and 20%, respectively, which was greater than the observed concordance between noncouples (10% for βHPV and 4% for γHPV). Transmission rate of βHPV between AG areas was 15.9 (95% confidence interval [CI], 3.3–46.5) per 100 person months for men-to-women at risk and for γHPV was 6.6 (95% CI, .2–36.7). Risks for women-to-men were similar.ConclusionsBeta and γHPV are common in the AG area, and data suggest that they can be sexually transmitted.

Cutaneous alpha, beta and gamma human papillomaviruses in relation to squamous cell carcinoma of the skin: a population-based study.

Human papillomavirus (HPV) infection is common worldwide and, in immunodeficient populations, may contribute to the pathogenesis of keratinocyte cancers, particularly squamous cell carcinomas (SCC). However, their role in SCC in the general population is less clear. We conducted a comprehensive analysis to investigate the independent effects of seropositivity for cutaneous alpha, beta and gamma HPV types on risk of SCC, and a meta-analysis of the available literature. In a population-based case-control study from New Hampshire, USA (n = 1,408), histologically confirmed SCC cases and controls were tested for L1 antibodies to alpha, beta and gamma cutaneous HPV types 2-5, 7-10, 15, 17, 20, 23, 24, 27b, 36, 38, 48-50, 57, 65, 75-77, 88, 92, 95, 96, 101, 103 and 107 using multiplex serology. An increasing risk of SCC with number of beta HPVs to which an individual tested positive was observed even among those seronegative for gamma types (p for trend = 0.016) with an odds ratio of 1.95 (95% confidence interval (CI) = 1.07-3.56) for four or more beta types positive. In a meta-analysis of six case-control studies, increased SCC risks in relation to beta HPV seropositivity were found across studies (meta odds ratio = 1.45, CI = 1.27-1.66). While the prevalence of gamma HPVs assayed was somewhat higher among SCC cases than controls, the association was only weakly evident among those seronegative for beta HPVs. Overall, the association between cutaneous HPVs and skin cancers appears to be specific to SCC and to genus beta HPVs in a general US population.

Papillomavirus infection in the conjunctiva of individuals with and without AIDS: An autopsy series from Uganda

HIV and genus beta human papillomavirus (HPV) types have been associated with squamous cell carcinoma of the conjunctiva (SCC). To determine whether conjunctival HPV infection is associated with AIDS, we analysed 136 lesion-free eye biopsies and tested for genera alpha, beta and gamma HPV types. Only infections with genera beta and gamma HPV types was found. After adjustment for age and gender, no excess of genera beta or gamma HPV infection was found in individuals who had died of or with AIDS compared to those who had died of other infectious diseases [relative risk (RR)=1.3; 95% confidence interval (CI): 0.4-4.8], or chronic diseases or trauma (RR=0.9; 95% CI: 0.3-2.9). Our findings suggest that infection with genera beta or gamma HPV types in lesion-free conjunctivas is common, but not greatly enhanced by the presence of AIDS.