Persistent Papillomavirus Research Articles

Spontaneous and post-interventional regression of cervical HPV infection.

Recent literature sources suggest that 15-20% of all malignant diseases have a viral aetiology. About 5% of these are caused by the human papillomavirus. The presence of papillomavirus is one of the strongest risk factors for development of a cervical pre-cancerous lesion and subsequent cervical cancer. The presented review provides a brief summary and characterisation of risk factors that influence spontaneous and post-interventional regression and persistence of papillomavirus in the cervical area.

Clinical errors in the diagnostic of cervical dysplasia. Clinical cases

Introduction: The cervical screening goal is to detect and treat precancers before cancer. We wanted to understand why errors in the clinical diagnostic and management of patients with persistence of human papillomavirus (HPV); infection occur in gynecological practice. Aim: Aim of the study was to evaluate 3 clinically important complications of situations for women aged 18-45 years. The study aimed to assess the diagnostic accuracy by colposcopy visualization, cytology and biopsy results, and presence of HPV infection. We aimed to analyze the false-negative (FN) cytology diagnoses inpatients with presence of HPV, colposcopy visualization, histologically proven cervical intraepithelial neoplasia (CIN) 2-3. Material and Methods: A retrospective analysis of errors in the management of patients was carried out, in treatment methods, especially with the use of cryodestruction, colposcopy pictures, results of cytological and histological conclusion, results of examination for oncogenic types of papillomavirus were presented. Discussion: After analyzing all errors in the management of patients with persistence of papillomavirus and preliminary cryotherapy of the cervix, the main reasons that led to the progression of the disease up to cervical cancer were noted. Conclusion: In the presence of papillomavirus, cryodestruction of the cervix is not advisable, even if no cervical dysplasia was detected by histological conclusions.

Endogenous oestradiol and progesterone as predictors of oncogenic human papillomavirus (HPV) persistence

BackgroundHigh-risk human papillomavirus (HR-HPV) is the main aetiological factor for the development of cervical cancer. While nearly 70% of HR-HPV infections are cleared within 12 months, in the remainder of women they persist and can progress into cervical cancer. Oestradiol and progesterone have been shown to be involved in the development and progression of cervical cancer. The objective of this study was to investigate, for the first time, whether diurnal oestradiol and progesterone are also involved in HR-HPV persistence – before cervical cancer develops.MethodsA total of N = 39 women between 18 and 31 years of age were investigated. All were nulliparous and regular users of combined oral contraceptives. Presence of HR-HPV was determined by cervical swabs. Salivary oestradiol and progesterone were measured upon awakening and at 11 am, 2 pm, and 5 pm. All HR-HPV positive women were re-tested in terms of HR-HPV status 12 months later.ResultsHR-HPV positive women had significantly higher morning (p = .007, partial eta2 = .221) and daily oestradiol levels (p < .001, partial eta2 = .442) when compared to HR-HPV negative women. In addition, those with persistent HR-HPV 12 months later had significantly elevated morning (p = .005, partial eta2 = .534) and daily (p = .027, partial eta2 = .346) oestradiol. Progesterone was found to be unrelated to HR-HPV.ConclusionsOestradiol was positively linked to HR-HPV presence and persistence. Provided that these findings are replicated, regular monitoring of oestradiol levels may prove useful in identifying women who are at risk of developing cervical cancer.

Cervical cancer: monitoring of the main indicators characterizing this pathology in Khabarovsk Krai (2009–2019)

Aim. Conduct a comparative assessment of the main indicators of the incidence of cervical cancer in Khabarovsk Krai (20092019) аnd the prevalence of types of human papillomavirus among the female population.&#x0D; Materials and methods. A comparative analysis of the data of the official statistics of the Ministry of Health of Khabarovsk Krai, using the Rosstat database for the period 20092019, taking into account the incidence, mortality, prevalence of types of human papillomavirus, was carried out. The dynamics trend was determined in the process of graphical analysis of the diagram and by modeling trends. The results of the studies were subjected to the methods of statistical information processing.&#x0D; Results. The results revealed in our study indicate that the increase in the incidence of cervical cancer in Khabarovsk Krai from 2009 to 2019 was 44.4% (with an average annual growth rate of 4.5%). Most often, cervical cancer in Khabarovsk Krai is detected in urban residents. The share of urban women with this pathology in 2019 reached 77.2%. The proportion of stage III cancer detected exceeds the proportion of stage IIIIV cancer by 2.5 times. Mortality in patients with cervical cancer in Khabarovsk Krai exceeds that in the Russian Federation. Of the 1617 residents of the city of Khabarovsk of reproductive age, 883 (54%) women had the presence of human papillomavirus. For our region, most often, women had highly oncogenic types of human papillomavirus 16, 56, 51.&#x0D; Conclusion. Statistical analysis based on the results of diagnosing early and advanced stages of cervical cancer, mortality from this nosological form, and the spread of the human papillomavirus remain among the most important criteria. The data obtained make it possible to assess the effectiveness of the chosen tactics in the regions and take timely corrective measures aimed at both early detection of cervical cancer and a decrease in the persistence of the human papillomavirus in women with background cervical pathology.

Persistent human papillomavirus infection in the genesis of reproductive losses. Prospects for therapy

Viral pandemics have shown that infected pregnant women are at risk of adverse pregnancy outcomes. Current evidence suggests that a pregnant woman’s immune system undergoes a transformation necessary to maintain pregnancy and fetal growth. The prevalence of human papillomavirus (PVI) is high, and its role in adverse pregnancy outcomes and reproductive loss is highly controversial. About 90% of cases of persistent human papillomavirus infection (PVI) are eliminated within one to two years. The role of the immune system in the elimination and persistence of PVI has been proven; however, there is no clear understanding of the mechanisms whereby PVI infected cells escape immune surveillance up to the present day. In addition, the immune mechanisms underlying the PVI persistence constitute a pathogenetic basis for the development of mechanisms of infertility, miscarriage and pregnancy pathology. Genetic polymorphism of the mother and the developing fetus, persistent PVI types and microbial landscape are modulating factors with an unexplained contribution in the transformation of quantity of introduced influences into the qualitative change in the biological state. The foreign and Russian research results analysed by the authors show that timely and adequate therapy of PVI may contribute to the preservation of reproductive potential and prevention of obstetric losses. The modern approach to the treatment of persistent PVI suggests the use of antiviral and immunomodulatory therapy. Due to its immunomodulatory and antiviral properties, inosine pranobex is used to treat viral diseases such as PVI, herpes simplex viruses, cytomegalovirus, Epstein-Barr virus and influenza.

Abstract A62: In vivo electroporation improves the immune responses induced by a DNA vaccine and confers complete antitumor protection against HPV-associated tumors

Abstract Cervical cancer associated with persistent papilloma virus infections (HPV) is a public health problem and represents the third most frequent type of cancer in women. Our group developed a DNA vaccine against HPV-induced tumors based on the expression of the HPV-16 E7 oncoprotein genetically fused to the HSV-1 glycoprotein D (gD) (pgDE7h). This vaccine is capable of promoting antitumoral effects against tumor cells expressing HPV-16 E6 and E7 proteins (TC-1 cells) and induces specific cellular immune responses. In view of the low success rate of DNA vaccines in clinical trials, in vivo electroporation (EP) is a promising strategy for plasmid delivery, leading to increased cellular transfection and enhanced immune responses. In this study, C57BL/6 mice were inoculated with TC-1 cells subcutaneously and immunized 3 days later with pgDE7h intramuscularly, associated or not with EP. Immune responses were analyzed 14 days after vaccination and tumor growth was monitored for 60 days. Similar antitumor effects were obtained with 10-fold less DNA associated with EP when compared to the group that was inoculated only with DNA, reaching around 20% of tumor-free mice. Dose-response curves indicated that maximum protective immunity was achieved with 50 ug of vaccine inoculated with EP, promoting 100% of antitumor protection. This group also had enhanced frequencies of cytotoxic lymphocytes expressing the degranulation marker CD107a and high in vivo cytotoxic activities. Besides that, a delayed vaccination performed 10 days after the TC-1 injection led to 70% of tumor-free mice until the end of the observed period. Collectively, these data confirmed that EP can be used as an efficient method of DNA vaccine delivery and should be further studied to improve the chances of cancer vaccine success in clinical trials. Citation Format: Natiely Silva Sales, Mariana de Oliveira Diniz, Jamile Ramos Silva, Mariângela de Oliveira Silva, Bruna F. M. M. Porchia, Luana R. M. M. Aps, Luis Carlos Souza Ferreira. In vivo electroporation improves the immune responses induced by a DNA vaccine and confers complete antitumor protection against HPV-associated tumors [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A62.

Стан системи імунітету у жінок з латентною папіломавірусною інфекцією шийки матки

The article presents modern aspects of the state of immunity in women with latent papillomavirus infection (PVI) of the cervix. The objective: the study of the indicators characterizing the state of immunity in women with latent PVI of the cervix, often associated with urogenital infections (UGI), at the beginning of the survey and after 6 months of observation. Patients and methods. The study of cellular and humoral immunity was performed in 210 women with latent papillomavirus infection (PVI) and 15 healthy women at the beginning of the examination and 6 months later. 84 women were diagnosed with a monoinfection, 126 had a combined PVI and a urogenital infection (UGI). In 140 women transient PVI is established, in 70 – persistent. Results. In women with latent cervical pylori cervix, disorders of cellular immunity were observed (a slight decrease in the relative amount of CD3+, CD4+ lymphocytes and a simultaneous increase in the number of CD8+ lymphocytes, natural killers and B-lymphocytes) against the background of activation of the humoral immunity unit. Nonspecific protection of the female body with PVI was characterized by inhibition of the phagocytic reaction of neutrophils (Nf) and monocytes (Mg) against the background of an increase in oxygen-dependent metabolism, primarily HF, and a decrease in the functional reserve for both NF and MZ. The most pronounced disorders were found for patients with combined PVI and UGI. Conclusion. In women with transient PVI normalization of cellular and humoral immunity was observed, and the further persistence of the human papillomavirus in the genitals led to a more significant inhibition of phagocytic and HCT activity of phagocytes, as well as to a decrease in some parameters of the cellular and humoral immunity units. Key words: papillomavirus infection, cervix, cellular and humoral immunity.

Human Papillomavirus Type 16 L2 DNA Methylation in Exfoliated Cervical Cells From College-Age Women: Erratum.

ObjectivesThe Carolina Women’s Care Study (CWCS) at the University of South Carolina followed 467 young women with the goal of identifying biomarkers of human papillomavirus (HPV) persistence. In this study, we analyzed the methylation of HPV16 DNA.MethodsThe aims of this study were to determine the

Interferon treatment of human keratinocytes harboring extrachromosomal, persistent HPV-16 plasmid genomes induces de novo viral integration.

Interferons (IFNs) have been used to treat epithelial lesions caused by human papillomavirus (HPV) persistence. Here, we exposed primary human keratinocytes (HFKs) immortalized by persistently replicating HPV-16 plasmid genomes to increasing levels of IFN-γ. While untreated HFKs retained replicating HPV-16 plasmids for up to 60-120 population doublings, IFN led to rapid HPV-16 plasmid loss. However, treated cultures eventually gave rise to outgrowth of clones harboring integrated HPV-16 genomes expressing viral E6 and E7 oncogenes from chimeric virus-cell mRNAs similar to those in cervical and head and neck cancers. Surprisingly, every HPV-16 integrant that arose after IFN exposure stemmed from an independent integration event into a different cellular gene locus, even within parallel cultures started from small cell inocula and cultured separately for ≥ 25 doublings to permit the rise and expansion of spontaneous integrants. While IFN treatment conferred a growth advantage upon preexisting integrants added to mixed control cultures, our results indicate that IFN exposure directly or indirectly induces HPV-16 integration, rather than only selects preexisting, spontaneous integrants that appear to be much less frequent. We estimate that IFN exposure increased integration rates by ≥ 100-fold. IFN-induced HPV-16 integration involved a wide range of chromosomal loci with less apparent selection for recurrent insertions near genes involved in cancer-related pathways. We conclude that IFNs and other potential treatments targeting high-risk HPV persistence that disrupt viral genome replication may promote increased high-risk HPV integration as a step in cancer progression. Therapies against high-risk HPV persistence thus need to be evaluated for their integration-inducing potential.

HPV prevalence at enrollment and baseline results from the Carolina Women&amp;rsquo;s Care Study, a longitudinal study of HPV persistence in women of college age

BackgroundCervical cancer, a rare outcome of high-risk human papillomavirus (HPV) infection, disproportionately affects African American women, who are about twice more likely than European American women to die of the disease. Most cervical HPV infections clear in about one year. However, in some women HPV persists, posing a greater risk for cervical dysplasia and cancer. The Carolina Women’s Care Study (CWCS) was conducted to explore the biological, genetic, and lifestyle determinants of persistent HPV infection in college-aged European American and African American women. This paper presents the initial results of the CWCS, based upon data obtained at enrollment.MethodsFreshman female students attending the University of South Carolina were enrolled in the CWCS and followed until graduation with biannual visits, including two Papanicolaou tests, cervical mucus collection, and a questionnaire assessing lifestyle factors. We recruited 467 women, 293 of whom completed four or more visits for a total of 2274 visits.Results and conclusionCWCS participants were 70% European American, 24% African American, 3% Latina/Hispanic, and 3% Asian. At enrollment, 32% tested positive for any HPV. HPV16 infection was the most common (18% of infections). Together, HPV16, 66, 51, 52, and 18 accounted for 58% of all HPV infections. Sixty-four percent of all HPV-positive samples contained more than one HPV type, with an average of 2.2 HPV types per HPV-positive participant. We found differences between African American and European American women in the prevalence of HPV infection (38.1% African American, 30.7% European American) and abnormal Papanicolaou test results (9.8% African-American, 5.8% European American). While these differences did not reach statistical significance at enrollment, as the longitudinal data of this cohort are analyzed, the sample size will allow us to confirm these results and compare the natural history of HPV infection in college-aged African American and European American women.

Human papillomavirus pevalence and persistence after chemoradiotherapy for carcinoma of the uterine cervix.

e15525 Background: Human papillomavirus (HPV) is associated with carcinoma of the cervix (CC). There is evidence that clearance of the virus occurs after chemoradiotherapy which is the standard treatment for this disease. Methods: Eligible patients with bulky IB to IVA CC were treated with once weekly cisplatin (40 mg/m2) chemotherapy and standard pelvic teletherapy and brachyterapy. HPV detection and typing was performed with DNA microarrays from liquid based cytologies before and 4 to 6 weeks after treatment completion. Clinical response was assesed by physical exam and liquid based cytology. Results: 23 patients (pt) with CC , were tested for HPV. Their age ranged from 33 to 80 years (mean 65), clinical stage I 8.6%, StageII 39%, stageIII 25.9% and stageIV 26.5%.VPH was found in 20 patients (87%). 34% of the patients had more than one type of HPV. 13 types of VPH were found,the most prevalent type was 16 in 47.8%, followed by type 72 in 13%.7 patients were lost to follow up during therapy. 16 patients were tested after completion of therapy ,there was HPV persistence in 5 patients (38.5%),whereas 61.5% cleared the virus. Of the persisting HPV the most prevalent type was 16 in two pt. and 61 in two pt. three pt had more than one HPV type after completion of therapy (types 11,81,35,39,56,84,66were found in different combinations in the pts). Response rate was as follows, 84.6% complete response,and two pt. had partial response. Viral clearance did not correlate with complete response in this study. Conclusions: HPV types 16 and 72 were the most prevalent in this population from northern Mexico. Infection with multiple viral types was common. Viral clearance occured in 61.5% and this did not correlate with complete clinical response. Persistence of multiple HPV types after completion of therapy may have unknown clinical and prognostic implications.

The Authors Respond to "HPV Persistence and Cervical Cancer Screening"

We thank Dr. Castle for his constructive and contributory commentary (1) on our meta-analysis of human papillomavirus (HPV) persistence and cervical neoplasia. We agree that ascertaining HPV persistence may have clinical utility and that several issues must be addressed before persistence can be effectively implemented in cervical screening programs. As Dr. Castle mentioned a single HPV test is more sensitive but less specific than a single Papanicolaou test for the detection of cervical precancer and cancer. In fact HPV testing at a single time point has approximately 20-40 percent higher sensitivity than Papanicolaou testing and 5-10 percent lower specificity. Incorporating HPV persistence into routine cervical cancer screening may help to improve specificity without unduly reducing sensitivity by distinguishing women with short-term infections and therefore lower risk of cervical precancer and cancer from women with long-term infections and therefore higher risk. (excerpt)

Persistence of Type-Specific Human Papillomavirus Infection among Cytologically Normal Women

Determinants of genital human papillomavirus (HPV) persistence in 393 women initially cytologically normal were investigated by testing them for HPV DNA twice over a median interval of 14.9 months. At each visit, interview information was obtained and a cervicovaginal lavage sample was collected for polymerase chain reaction-based HPV testing. Twenty-six percent of the women were HPV-positive at the first sampling. Data on HPV type was available for 86 HPV-positive women (84%); 35 of these women (41%) had persistent type-specific HPV detection. Persistence decreased with time between samplings. Women aged > or = 30 years had a higher percentage of persistence (65%) than those < or = 24 years (32%, P = .02). The percentage of persistence was higher among women infected with HPV types known to be cancer-associated (45%) than among those infected with other types (24%, P = .11). These findings were independent of each other and of timing between samplings. Although based on a prevalent cohort, these results are concordant with previous suggestions that HPV infection is usually transient and that cervical cancer may arise from within the subset of women with persistent HPV infection.

Persistence of bovine papillomavirus (pBPV-1) as an extrachromosomal element in tissues of microinjectedXenopus laevis

Persistence of bovine papillomavirus (pBPV-1) as an extrachromosomal element in tissues of microinjected<i>Xenopus laevis</i>

Immunofluorescent study on early virus-cell interaction in Shope papilloma in vitro system.

Discussion and ConclusionEmbryonic skin culture of domestic rabbit was infected with Shope papilloma virus in vitro and the early phase of virus-cell interaction was studied sequentially up to 30-hours post infection by the immunofluorescence technique. The cells of infected cultures showed a specific fluorescent reaction in the nucleus when stained with antipapilloma antisera conjugated with FITC. The ratio of positively stained cells was about 20% of the whole cell population in cultures 5-6 hours after infection with the virus and it reached a maximum of approximately 90% at around 11 hours. The morphological pattern of the intranuclear fluorescent staining was reminiscent of the reaction of T antigen reported in the SV40-infected hamster cells (6).Kreider et al. (7) have recently reported their findings on the persistence of Shope papilloma virus absorbed onto the cell surface of cells of in vitro cultured embryonic skin of rabbits. The viral antigen was detectable in cultured cells even after 6-days ...