scholarly journals High Risk Human Papillomavirus genital infections in asymptomatic population: effectiveness of Micro-Immunotherapy

2021 ◽  
Vol 11 (40) ◽  
pp. 134-135
Author(s):  
Sandra Mazzoli ◽  
Tommaso Cai ◽  
Francesca Meacci ◽  
Patrizia Addonisio ◽  
Pierre Dorfman
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Viral Infections ◽  
Interleukin 1 ◽  
Interleukin 2 ◽  
Hpv Infection ◽  
Exact Test ◽  
Hpv Dna ◽  
Asymptomatic Patients

Background: persistent infection with high-risk human papillomavirus (HR-HPV) is the primary cause for the development of various anogenital cancers in females and males. Most infections are either latent or subclinical and the majority occur as asymptomatic. HPV infections are not currently treatable by antiviral compounds. Micro-immunotherapy (MI) medications using high dilutions of cytokines and specific nucleotide sequences have been developed to treat targeted viral infections and are currently prescribed in medical practice as immune regulators: 2L®PAPI (Labo’Life) is indicated for HPV infection and may represent a new therapeutic approach. Aims: this exploratory study was to assess the effectiveness of 2L®PAPI on HPV infection eradication in HR-HPV infected asymptomatic patients attending an STD Centre in a long-term microbiological follow-up population survey. Methodology: adult patients of both genders, diagnosed with HR-HPV infection, with no evidence of symptomatic HPV or anogenital cancer, were followed during a 2 year-period (2009-2010). Selected patients had not previously been vaccinated for HPV or treated with medications having an impact on the immune system. HPV testing was performed on biological samples using PCR detection (Innogenetics, Italy). In addition, detection of E6/E7 mRNA of five carcinogenic HPV types was performed by EasyQ HPV (BioMerieux, Italy). HPV-positives were requested by their urology specialist to take 2L®PAPI (composition in table 1) during 4 months (1 caps/day by sublingual route). Globally 46 patients were followed: 23 treated with MI medication, and 23 not treated. Results: one third of selected patients were lost at the control visit (15/46). At the end of the study period, HR-HPV negativity was observed in 50% (8/16) of patients under MI medication in comparison with only 7% (1/15) of the non treated patients who were HPV-DNA negative at the follow-up visit (p=0.01071, Mid-P exact test). This result is in accordance with our previous results which showed long lasting persistence of HR-HPV infection in a male cohort. Conclusions: the relevant percentage of lost patients at follow-up reflects the scarce information and awareness of this infection within asymptomatic people in Italy. 2L®PAPI was efficient in eradicating 50% of HR-HPV infections in treated patients, including 60% of HPV-16. These promising data emphasize the importance of redirecting immune responses in viral infections. Table 1: 2L®PAPI composition Compounds Dilutions Interleukin-1 (IL-1): 17-10 CH* Interleukin-2 (IL-2): 17-10 CH Interferon-α (IFN-α): 17-10 CH SNA-HLA II: 16-10 CH Ciclosporin A (CsA): 7-10-17 CH Ribonucleic acid (RNA): 18-10 CH SNA-PAPI: 16-10 CH * CH: Centesimal Hahnemannian (1/100)

scholarly journals Genome-Wide Association Study of Prevalent and Persistent Cervical High-Risk Human Papillomavirus(HPV) Infection

2019 ◽  
Author(s):  
Sally N. Adebamowo ◽  
Adebowale A Adeyemo ◽  
Charles N Rotimi ◽  
Olayinka Olaniyan ◽  
Richard B. Offiong ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Principal Component ◽  
Hpv Infection ◽  
Genome Wide Association ◽  
Replication Studies ◽  
Genome Wide

Abstract Background: Genetic factors may influence the susceptibility to high-risk human papillomavirus (hrHPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence. Methods: Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes. Results: The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p=1.43 x 10-6). The top variants associated with cervical hrHPV persistence were in DAP(OR: 6.86, p=7.15 x 10-8), NR5A2(OR: 3.65, p=2.03 x 10-7) and MIR365-2(OR: 7.71, p=2.63 x 10-7) gene regions. Conclusions: This exploratory GWAS yielded novel candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

scholarly journals The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 786
Author(s):  
Ryan T. Gibson ◽  
Elliot J. Androphy
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Viral Replication ◽  
Chromatin Immunoprecipitation ◽  
Binding Sites ◽  
Viral Infections ◽  
Hpv Infection ◽  
Regulatory Proteins ◽  
Transactivation Domain ◽  
Structural Maintenance Of Chromosomes

The multi-subunit structural maintenance of chromosomes (SMC) 5/6 complex includes SMC6 and non-SMC element (NSE)3. SMC5/6 is essential for homologous recombination DNA repair and functions as an antiviral factor during hepatitis B (HBV) and herpes simplex-1 (HSV-1) viral infections. Intriguingly, SMC5/6 has been found to associate with high-risk human papillomavirus (HPV) E2 regulatory proteins, but the functions of this interaction and its role during HPV infection remain unclear. Here, we further characterize SMC5/6 interactions with HPV-31 E2 and its role in the HPV life cycle. Co-immunoprecipitation (co-IP) revealed that SMC6 interactions with HPV-31 E2 require the E2 transactivation domain, implying that SMC5/6 interacts with full-length E2. Using chromatin immunoprecipitation, we found that SMC6 is present on HPV-31 episomes at E2 binding sites. The depletion of SMC6 and NSE3 increased viral replication and transcription in keratinocytes maintaining episomal HPV-31, indicating that SMC5/6 restricts the viral replicative program. SMC6 interactions with E2 were reduced in the presence of HPV-31 E1, suggesting that SMC6 and E1 compete for E2 binding. Our findings demonstrate SMC5/6 functions as a repressor of the viral replicative program and this may involve inhibiting the initiation of viral replication.

scholarly journals Detection and estimation of human papillomavirus viral load in patients with cervical lesions

2014 ◽  
Vol 39 (2) ◽  
pp. 86-90 ◽  
Author(s):  
T Rahman ◽  
S Tabassum ◽  
M Jahan ◽  
A Nessa ◽  
Dr Ashrafunnessa
Keyword(s):  
Human Papillomavirus ◽  
Viral Load ◽  
High Risk ◽  
Invasive Cervical Cancer ◽  
Hpv Infection ◽  
Cervical Lesions ◽  
Hpv Dna ◽  
Promising Tool ◽  
High Risk Hpv ◽  
Hpv Viral Load

Human papillomavirus (HPV) high risk genotype infection and HPV viral load influences the development of invasive cervical cancer and cervical intra-epithelial neoplasia (CIN). HPV DNA testing for screening of cervical cancers may play a potential role in its early detection and management. The present study detected HPV DNA and estimated HPV viral load in different types of cervical lesions among Bangladeshi women. Using the Hybrid Capture 2 (HC2) assay, HPV DNA was tested among 68 women between 25-70 years of age. A total of 13 (19.1%) cases were positive for HPV DNA. The highest viral load (501 x 10³ copies/ml) was detected in a patient with invasive carcinoma, while the lowest viral load (105 x 10³ copies/ml) was detected from a case of chronic cervicitis. The mean viral load in CIN I was 119.25 x 10³±12.5 x 10³ copies/ml (range: 110 x 10³ - 137 x 10³) and 208.50 x 10³ ± 0.59 x 10³ copies/ml (range: 139 x 10³-305 x 10³) in CIN II / III. Interestingly, HPV DNA was detected from a patient with normal cytological findings. Our study observed a moderate presence of high-risk HPV genotypes among women with cervical lesions. The HPV viral load varied with the age of the patients and stage of cervical lesions. The HC2 assay is a promising tool for diagnosing high-risk HPV infection especially before cytology tests show any abnormality. DOI: http://dx.doi.org/10.3329/bmrcb.v39i2.19648 Bangladesh Med Res Counc Bull 2013; 39: 86-90

scholarly journals The Relationship between Cocaine Use and Human Papillomavirus Infections in HIV-Seropositive and HIV-Seronegative Women

2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Howard Minkoff ◽  
Ye Zhong ◽  
Howard D. Strickler ◽  
D. Heather Watts ◽  
Joel M. Palefsky ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Pap Smear ◽  
Crack Cocaine ◽  
Hpv Infection ◽  
Cocaine Use ◽  
Hpv Dna ◽  
Increased Risk ◽  
Hiv Seropositive ◽  
Oncogenic Hpv

Objective. Animal data suggest that cocaine has an immunosuppressive effect, but no human studies have been conducted to assess the relation of cocaine use with human papillomavirus (HPV) infection, the viral cause of cervical cancer. Since both cocaine use and HPV infection are common among HIV-positive women, we sought to determine whether use of cocaine and/or crack influences the natural history of HPV among women with or at high risk of HIV.Methods. Women enrolled in the Women's Interagency HIV Study (2278 HIV-seropositive and 826 high-risk seronegative women) were examined every six months for up to 9.5 years with Pap smear, collection of cervicovaginal lavage (CVL) samples, and detailed questionnaires regarding health and behavior, including use of crack and cocaine (crack/cocaine). CVLs were tested for HPV DNA by PCR, with genotyping for over forty HPV types.Results. In multivariate logistic regression models, censoring women treated for cervical neoplasia, crack/cocaine use within the last six months was associated with prevalent detection of oncogenic HPV DNA (odds ratio [OR] = 1.30 (1.09–1.55)), and with oncogenic HPV-positive squamous intraepithelial lesions (SIL) (OR = 1.70 (1.27–2.27)), following adjustment for age, race, HIV-serostatus, and CD4+ T-cell count, the number of sexual partners in the past six months, and smoking. In multivariate Cox models crack/cocaine use was also associated with a trend that approached significance in regard to incident detection of oncogenic HPV-positive SIL (HR = 1.51, 95% CI 0.99–2.30), and while the rate of oncogenic HPV clearance was not related to cocaine use, the clearance of any SIL was significantly lower in those with versus those without recent crack/cocaine use (HR = 0.57, 95% CI 0.34–0.97).Conclusions. Cocaine use is associated with an increased risk of detection of both prevalent and incident oncogenic HPV infection, as well as an increased risk of HPV-positive SIL over time.

scholarly journals Modelling human papillomavirus biology in oropharyngeal keratinocytes

2019 ◽  
Vol 374 (1773) ◽  
pp. 20180289 ◽  
Author(s):  
Sally Roberts ◽  
Dhananjay Evans ◽  
Hisham Mehanna ◽  
Joanna L. Parish
Keyword(s):  
Human Papillomavirus ◽  
Viral Infections ◽  
Hpv Infection ◽  
Oral Route ◽  
Neoplastic Progression ◽  
Hpv Dna ◽  
Human Dna ◽  
Cervical Disease ◽  
High Risk Type ◽  
History Of

Most human papillomavirus (HPV) positive head and neck cancers arise in the tonsil crypts; deep invaginations at the tonsil surface that are lined with reticulated epithelium infiltrated by immune cells. As in cervical HPV infections, HPV16 is the most prevalent high-risk type in the oropharyngeal cancers, and a genital-oral route of infection is most likely. However, the natural history of HPV-driven oropharyngeal pathogenesis is an enigma, although there is evidence that it is different to that of cervical disease. It is not known if the virus establishes a productive or abortive infection in keratinocytes of the tonsil crypt, or if viral infections progress to cancer via a neoplastic phase, as in cervical HPV infection. The HPV DNA is more frequently found unintegrated in the cancers of the oropharynx compared to those that arise in the cervix, and may include novel HPV-human DNA hybrids episomes. Here, we review current understanding of HPV biology in the oropharynx and discuss the cell-based systems being used to model the HPV life cycle in tonsil keratinocytes and how they can be used to inform on HPV-driven neoplastic progression in the oropharynx. This article is part of the theme issue ‘Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses’.

scholarly journals Genome-wide association study of prevalent and persistent cervical high-risk human papillomavirus (HPV) infection

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Sally N. Adebamowo ◽  
◽  
Adebowale A. Adeyemo ◽  
Charles N. Rotimi ◽  
Olayinka Olaniyan ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Principal Component ◽  
Hpv Infection ◽  
Genome Wide Association ◽  
Replication Studies ◽  
Genome Wide

Abstract Background Genetic factors may influence the susceptibility to high-risk (hr) human papillomavirus (HPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence. Methods Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done for hrHPV infection (125 cases/392 controls) and for persistent hrHPV infection (51 cases/355 controls) under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes. Results The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. No single variant reached genome-wide significance (p < 5 X 10− 8). The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p = 1.43 × 10− 6). The top variants associated with cervical hrHPV persistence were in DAP (OR: 6.86, p = 7.15 × 10− 8), NR5A2 (OR: 3.65, p = 2.03 × 10− 7) and MIR365–2 (OR: 7.71, p = 2.63 × 10− 7) gene regions. Conclusions This exploratory GWAS yielded suggestive candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

Persistence of human papillomavirus as a predictor for treatment failure after loop electrosurgical excision procedure

2007 ◽  
Vol 17 (6) ◽  
pp. 1271-1277 ◽  
Author(s):  
J. H. Bae ◽  
C. J. Kim ◽  
T. C. Park ◽  
S. E. Namkoong ◽  
J. S. Park
Keyword(s):  
Human Papillomavirus ◽  
Treatment Failure ◽  
Significant Risk ◽  
Hpv Infection ◽  
Dna Chip ◽  
Hpv Dna ◽  
Hpv Test ◽  
Loop Electrosurgical Excision ◽  
Loop Electrosurgical Excision Procedure

We aimed to investigate whether postconization human papillomavirus (HPV) DNA testing can predict treatment failure and improve the accuracy of conventional follow-up in women with high-grade cervical intraepithelial neoplasia (CIN). Between March 2001 and October 2005, 120 patients with confirmed CIN 2 or 3 were treated with loop electrosurgical excision procedure (LEEP) and were enrolled. Six patients were lost to the follow-up. Postconization follow-up was performed at every 3–6 months during the first year and then annually. Specimens were tested for the presence of HPV, using the Hybrid Capture 2 (Digene Co, Gaithersburg, MD) and HPV DNA chip (Mygene Co, Seoul, Korea) test. Persistent HPV infection was defined as persistently (two times or more) positive HPV tests with the same HPV subtype(s) at initial diagnosis. Twenty-two (19.3%) patients showed treatment failure after conization. The only significant risk factor for redevelopment of CIN after conization was persistence of the same HPV subtype (P< 0.0001). And women with recurrent or residual CIN had higher HPV load during the 6-month follow-up postconization. In conclusion, the persistence of the same HPV subtype after LEEP conization was an important predictor of treatment failure. The follow-up protocol after conization of CIN should include both cervical cytology and HPV test, and HPV DNA chip test is needed to detect a persistent HPV infection.

scholarly journals Identification of High-Risk Human Papillomavirus DNA, p16 and E6/E7 Oncoproteins in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1008
Author(s):  
Andrejs Lifsics ◽  
Valerija Groma ◽  
Maksims Cistjakovs ◽  
Sandra Skuja ◽  
Renars Deksnis ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Squamous Cell ◽  
Surrogate Marker ◽  
Hpv Infection ◽  
Hpv16 E6 ◽  
Hpv Dna ◽  
Molecular Virology ◽  
Hpv E6 ◽  
E6 And E7

Human papillomavirus (HPV) was proven to play a significant role in cancer development in the oropharynx. However, its role in the development of laryngeal (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) remains to be clarified. High-risk HPV (HR-HPV) viral proteins E6 and E7 are considered to be pertinent to HPV-related carcinogenesis. Hence, our aim was to estimate LSCC and HPSCC for HR-HPV DNA, p16, and E6/E7 oncoprotein status by using molecular virology and immunohistochemistry methods. The prevalence of HPV16 infection was 22/41 (53.7%) and 20/31 (64.5%) for LSCC and HPSCC, accordingly. The majority of HPV16+ tumor samples were stage III or IV. In most samples, the presence of either HPV16 E6 or HPV16 E7 viral protein in dysplastic or tumor cells was confirmed using immunohistochemistry. Our results suggest a high prevalence of HPV16 as a primary HR-HPV type in LSCC and HPSCC. The lack of HPV E6/E7 oncoproteins in some tumor samples may suggest either the absence of viral integration or the presence of other mechanisms of tumorigenesis. The utilization of p16 IHC as a surrogate marker of HR-HPV infection is impractical in LSCC and HPSCC.

scholarly journals IL-6 and IL-10 in the serum and exfoliated cervical cells of patients infected with high-risk human papillomavirus

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248639
Author(s):  
Camila Mareti Bonin-Jacob ◽  
Larissa Zatorre Almeida-Lugo ◽  
Marco Antonio Moreira Puga ◽  
Ana Paula Machado ◽  
Cacilda Tezelli Junqueira Padovani ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Uterine Cervix ◽  
Hpv Infection ◽  
Single Infection ◽  
Multiple Infections ◽  
Neoplastic Progression ◽  
Cervical Lesions ◽  
Hpv Dna ◽  
Cervical Cells

Persistent infection by high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer and its precursor lesions. While some cytokines help immune cells in virus clearance, others contribute to the persistence of infection and neoplastic progression. Here, the levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-10, IL-6, IL-4, and IL-2 were quantified in the serum and exfoliated cervical cells (ECCs) of patients with HR-HPV, and the presence of IL-6+ cells was investigated in uterine cervix biopsies. Cytokine levels in the serum and ECCs of 26 HR-HPV DNA-positive patients and 18 HPV DNA-negative patients were measured using flow cytometry. Fifteen uterine cervix biopsy samples embedded in paraffin were subjected to immunohistochemical analysis for the detection of IL-6+ cells. HR-HPV-positive patients showed increased IL-6 and IL-10 in the ECCs and serum, respectively. Compared with HPV DNA-positive patients, HPV DNA-negative patients had higher levels of IL-6 in ECCs. Patients with multiple infections of HPV had higher levels of IL-6 in their ECCs than those with a single infection. Immunostaining of uterine cervix biopsy samples revealed no differences in IL-6 expression between the different classes of histopathological lesions. However, differences were observed in the expression levels of IL-6 and IL-10 at the systemic and local levels in HR-HPV-positive patients without cervical lesions. Considering the functional characteristics of these cytokines, it can be inferred that such patients are prone to persistent HPV infection.

scholarly journals Modern concepts of epidemiologyHPV-infection

2013 ◽  
Vol 62 (5) ◽  
pp. 3-14
Author(s):  
Kseniya Yevgenyevna Semenova ◽  
Armine Robertovna Khachaturyan
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Age Groups ◽  
Treatment Strategies ◽  
Hpv Infection ◽  
Dna Testing ◽  
Transmitted Infection ◽  
Hpv Dna ◽  
Sexually Transmitted ◽  
Hpv Dna Testing

Human papillomavirus (HPV) is widespread sexually transmitted infection, which is defined by high risk of contagion and high cancer potential. HPV extension depends on patiens age, residence, opportunites of diagnostics, etc. There are general methods of HPV-diagnostics such as HPV DNA testing, cytological, hystological methods, which are not always useful in detection of transitory and persistent HPV-infection forms. Nowadays, there is acute need to develop new diagnostic and prognostic methods, treatment strategies for patients from various age groups, having different infection formss.

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