Course Of Human Papillomavirus Infection Research Articles

What a patient needs to know about the virus human papillomas and cervical cancer?

According to experts of the World Health Organization, cervical cancer is the only cancer that can be completely prevented through the introduction of mass screening and educational information in the population. One of the activities of the obstetrician-gynecologist is the conduct of health education. However, for a variety of reasons, a practical doctor may have difficulty preparing for informational and educational meetings with patients.
 Aim. To prepare a clinical lecture for the obstetrician-gynecologist, which can be used in educational work with the population on the prevention of human papillomavirus infection and cervical cancer.
 Materials and methods. The information material includes data from foreign and domestic scientific articles available at PubMed on this topic and published over the past 10 years.
 Results. A systematic analysis of the data contained in the modern literature on human papillomavirus, human papillomavirus infection and cervical cancer has been carried out. Information is presented on the prevalence of diseases, diagnostic methods, and features of the course of human papillomavirus infection, the role of human papillomavirus in the development of cervical cancer. Attention is drawn to the importance of preventive examinations. Part of the information is presented in the form of answers to patients questions, which makes the information presented especially memorable.
 Conclusion. It is hoped that the prepared lecture will be useful for the educational work of the obstetrician-gynecologist and will increase the educational information of the population on the prevention of cervical cancer.

Characterization of cervical biopsies of women with HIV and HPV co-infection using p16ink4a, ki-67 and HPV E4 immunohistochemistry and DNA methylation

This study aims to characterize cervical intraepithelial neoplasia (CIN) in women living with HIV using biomarkers. Immunohistochemical (IHC) staining for human papillomavirus (HPV) E4 protein indicates CIN with productive HPV infection, whereas Ki-67 and p16ink4a indicate CIN with transforming characteristics, which may be further characterized using DNA hypermethylation, indicative for advanced transforming CIN. Cervical biopsies (n = 175) from 102 HPV positive women living with HIV were independently reviewed by three expert pathologists. The consensus CIN grade was used as reference standard. IHC staining patterns were scored for Ki-67 (0–3), p16ink4a (0–3), and E4 (0–2) and correlated to methylation levels of four cellular genes in corresponding cervical scrapes. Reference standards and immunoscores were obtained from 165 biopsies:15 no dysplasia, 91 CIN1, 31 CIN2, and 28 CIN3. Ki-67 and p16ink4a scores increased with increasing CIN grade, while E4 positivity was highest in CIN1 and CIN2 lesions. E4 positive CIN1 lesions had higher Ki-67 and p16ink4a scores and higher methylation levels compared with E4 negative CIN1 lesions. E4 positive biopsies with low cumulative Ki-67/p16 ink4a immunoscores (0-3) had significantly higher methylation levels compared with E4 negative biopsies. No significant differences in Ki-67 and p16ink4a scores and methylation levels were observed between E4 negative and positive CIN2 or CIN3 lesions. The presence of high methylation levels in scrapes of CIN lesions with IHC characteristics of both productive (E4 positive) and transforming infections (increased Ki-67/p16ink4a expression) in women living with HIV might indicate a rapid aggressive course of HPV infections towards cancer in these women.

ВПЧ-ассоциированные заболевания шейки матки. Возможности комплексной терапии

Human papillomavirus (HPV) is one of the most common groups of viruses that has infected more than 660 million people in the world. It has been proved that the long persistence of HPV in the tissues of the organs of the lower part of the genital tract provokes the development of precancerous and cancerous processes. Since the state of the immune system largely determines the nature of the course of HPV infection, a modern approach to the treatment of HPV-associated diseases involves the use of antiviral and immunomodulatory therapy.

Human papillomavirus DNA positivity and seropositivity in rural Chinese men and women: a population-based cross-sectional study.

Data on simultaneous analysis of human papillomavirus (HPV) DNA and serology and the correlations within a single general population are limited. Among 1603 men and 2187 women enrolled from rural China, serum antibodies against bacterially derived GST-L1 fusion proteins of HPV were assessed with multiplexed serology and HPV DNA was evaluated with PCR-based sequencing. Few subjects were dually positive to HPV DNA and serum antibodies for any HPV (6.6% of men and 3.1% of women). The proportion of men ever having been infected with any HPV (DNA and/or antibody positive) was higher than that of women (71.0% vs. 65.2%, P < 0.001). Type-specific association was observed for genital HPV infection and HPV seropositivity among women but not among men. A positive correlation between the number of lifetime sexual partners and positivity for oncogenic HPV DNA and/or antibodies was found in men but was absent in women. Among 762 couples, the presence of HPV DNA and/or antibodies in one partner was positively associated with the identical HPV type in the other partner. These findings may reflect a site-specific natural course of HPV infection and further understanding of the epidemiology of HPV.

Establishment of immunoassay for detecting HPV16 E6 and E7 RNA.

Cervical carcinoma is the most prevalent malignancy second only to breast cancer among women worldwide. Since more than 99% of cervical cancers are caused by human papilloma virus (HPV), measurement of HPV (HPV test) was commonly used in screening risk and/or early stage of cervical cancer as well as assessing the efficacies of the treatments that can decrease the incidence of cervical cancer. Many approaches that diagnose HPV infections have been developed, while most of them have distinct shortcomings. We here established a novel immunoassay method in which the pairs of unlabeled DNA probes firstly bind to HPV16 E6 and E7 RNAs to form the DNA-RNA hybrids, and the hybrids will subsequently be identified by S9.6 antibody. The sensitivity of this highly specific method can reach ~0.923 pg/mL and ~0.424 pg/mL of in vitro transcribed HPV16 E6 and E7 RNA, respectively, and reverse transcription and polymerase chain reaction (PCR) amplification were no longer needed. Thus, our immunoassay approaches can precisely reflect the actually viral load that is related to the course of HPV infection. In addition, it has also fast and low cost characteristic feature.

Early detection of CIN3 and cervical cancer during long-term follow-up using HPV/Pap smear co-testing and risk-adapted follow-up in a locally organised screening programme

We evaluated compliance with human papillomavirus (HPV) testing and risk-adapted patient pathways and monitored changes in high-grade cervical disease during long-term follow-up. Women aged >30 years attending routine screening for cervical cancer were managed according to results from first-round screening tests (cytology and high-risk HPV; Hybrid Capture 2). Between February 2006 and January 2011, 19,795 of 19,947 women agreed to participate, of whom 4,067 proceeded to a second screening round 5 years after recruitment. Predefined endpoints were compliance, grade 3 cervical intraepithelial neoplasia or cancer (CIN3+), new HPV infection, HPV persistence and abnormal smears in round 2. A total of 765 of 19,795 women (3.9%) in round 1 and 41 of 4,067 (1.0%) in round 2 were referred for colposcopy. Compliance rates with colposcopy were 93.1 and 92.7%, respectively, while histological assessment was performed in 680 of 712 (95.5%) and 36 of 38 (94.7%), respectively. CIN3+ rates were 172 of 19,795 (0.87%; 95% confidence intervals: 0.7-1.0) in round 1 and 2 of 4,064 (0.05%; 95% confidence intervals: 0.006-0.2) in round 2; the difference was statistically significant (Fisher's exact test, p<0.001). After 5 years, the incidence of new HPV infection was 124 of 3,906 (3.2%) and HPV persistence was observed in 22 of 161 (13.7%). Locally organised HPV/cytology co-testing is feasible and acceptable to women. Risk-adapted management rapidly detected a high rate of prevalent CIN3+, while the subsequent long-term risk of new high-grade cervical disease was surprisingly low. It remains unclear if this phenomenon is explained by CIN3 mostly occurring early in life or by modifying the natural course of HPV infection with colposcopy and histological assessment.

Abnormal Cytology in 2012

Cervical cancer and human papillomavirus-related diseases continue to cause significant morbidity and mortality in the United States and worldwide. As we begin to understand the natural course of human papillomavirus infection, and the consequences of both its detection and treatment, changes have been made to our clinical approaches. The purpose of this review is to outline the management guidelines for the management of abnormal cytology. Successful triage of abnormal cytology in 2012 will allow for continued detection of precancerous lesions reducing the incidence of cervical cancer and increasing the detection of early stage disease.

Caring for Women With Abnormal Papanicolaou Tests During Pregnancy

The Papanicolaou (Pap) test is one of the best screening tests available for cancer detection and has achieved widespread acceptance among women. Pregnancy provides a valuable opportunity to educate and screen women for cervical cancer when receiving prenatal care. However, evolving knowledge about the course of human papillomavirus infection (HPV) in women, new technologies, and the advent of vaccines are driving radical changes in practice and new ways to consider cervical cancer screening. Modifications in the 2006 Consensus Guidelines for the Management of Women with Abnormal Cervical Cancer Screening Tests are most evident among adolescents. Because of high rates of HPV regression, pregnant adolescents with minor Pap abnormalities may now be followed rather than referred for immediate colposcopy. Postponing colposcopy in pregnant, reproductive-age women with minor Pap changes until after delivery is now acceptable. Pregnant immunocompromised women with abnormal Pap tests are followed similarly to pregnant women in the general population. While a strong evidence base is gradually emerging to support guideline revisions, the highest quality evidence may not yet be available for all recommendations. Midwives can keep abreast of the science while using clinical judgment to provide safe and expert cancer screening care to women.

Prevalence, incidence and clearance of human papillomavirus infection among young primiparous pregnant women in Kampala, Uganda

The proportion of women who have already been exposed to human papillomavirus (HPV) infection by the time they first become pregnant, and the influence of pregnancy and delivery on the course of HPV infection are unclear. In Kampala, Uganda, 987 young primiparous pregnant women aged <25 years had gynaecological examination and liquid-based cytology. In the follow-up, women acted as their own controls, i.e., 1st/2nd versus 3rd trimesters (105 women), and during pregnancy versus after delivery (289 women). HPV was assessed using highly sensitive PCR assays. Prevalence of HPV and HIV infections at baseline were 60.0% and 7.3%, respectively. HPV16 and 18 were detected in 8.4% and 5.8%, respectively, i.e., less frequently than HPV51 (8.7%) and 52 (12.1%). At follow-up new HPV infections were detected in 42.9% of women between the 1st/2nd and 3rd trimesters, and 38.1% between pregnancy and delivery, but 50.4% and 71.8% of HPV infections, respectively, cleared, leaving HPV prevalence unchanged in the different periods. Prevalence of cytological abnormalities diminished after delivery (from 21.2% to 12.4%). Presence of genital warts and sexually transmitted infections other than HPV were the strongest risk factors for prevalent or incident HPV infection. Clearance was lower among HIV-positive women. In conclusion, HPV prevalence was high in primiparous women in Uganda, but pregnancy did not seem to be a period of special vulnerability to the infection.

Predictive testing of early cervical pre-cancer by detecting human papillomavirus E6/E7 mRNA in cervical cytologies up to high-grade squamous intraepithelial lesions: Diagnostic and prognostic implications

The type-specific persistence of oncogenic human papillomavirus (HPV) is considered to be the true precursor of cervical cancer at which the transcription of the viral oncogenes E6 and E7 is necessary for the malignant transformation and maintenance of the neoplastic state. In the present pilot study, a cohort of 66 women was investigated from a routine office-based screening population who had an index cytological result from normal to high-grade squamous intraepithelial lesions and who were also HPV-DNA positive for at least one of the following high-risk HPV types: HPV 16, 18, 31, 33 and 45 detected by MY09/MY11 consensus and GP5+/6+ general primers, followed by sequencing. The expression of E6/E7 transcripts from the same HPV types was detected by the PreTect HPV-Proofer. Cervical status was checked 18 months after the mRNA test. The expression of E6/E7 mRNA was found in 58% of the cases showing a 97% concordance with the HPV-DNA types and a positive correlation with increasing cytological and histological grade. All HPV-mRNA positive cases were also positive for HPV DNA whereas 25 (38%) of the HPV-DNA positive cases did not express the respective mRNA. The diagnostic validity of the PreTect assay for detecting histologically-proven prevalent CIN3 lesions were: sensitivity 95%, specificity 55%, positive predictive value (PPV) 81% and negative predictive value (NPV) 86%. The prognostic power of the PreTect test for predicting cytological disease progression was as follows: 78% sensitivity, 60% specificity, 37% PPV and 90% NPV. In conclusion, our results showed that the detection of oncogenic HPV E6/E7 mRNA in cervical smears in a routine screening setting identifies prevalent CIN3 lesions with nearly 100% sensitivity and has a very high negative predictive value for disease progression during the natural course of HPV infection. Thus, testing for HPV oncogenic activity may be used as a clinically predictive marker to enhance the net effectiveness of screening and enable the prognostication of prevalent cervical lesions.

Human papillomavirus infection in Rio de Janeiro, Brazil: a retrospective study

There is considerable data to support a central role for human papillomavirus (HPV) in the etiology of cervical cancer. More than a 100 HPV types have been described, and 40 have been isolated from benign and malignant genital lesions. Consequently, there is strong motivation to evaluate HPV testing for cervical cancer screening. Few studies concerning the natural history of HPV infection have been conducted in the state of Rio de Janeiro. We determined the prevalence of HPV types in female genital lesions by using Hybrid Capture Assay (HCA) and we retrospectively analyzed the course of HPV infection. Our sample included 788 women attended at Laboratórios Sérgio Franco. The average age of the participants was 29.6 years. HPV prevalence and cytological diagnosis were determined. The overall prevalence of HPV DNA in the study group was 50.1% (395/788), ranging from 25% (NORMAL) to 100% in high-grade intraepithelial lesions (HSIL). High risk HPV was found in 12% inflammatory, 58.3% HPV, 63.2% LSIL and 100% HSIL. A retrospective analysis of 78 patients showed that 22 presented persistent lesions, 2 had progressive lesions, 4 had regressive lesions, 13 showed latent infections, 18 were transiently infected and 19 were submitted to curative treatment. No cases of cancer were registered in this population, which can afford private medical care and regular follow-up exams. We suggest that HCA be used in specific cases involving persistent and recurrent lesions.

Epidermal Growth Factor Receptor, c-erbB-2 Proto-Oncogene and Estrogen Receptor Expression in Human Papillomavirus Lesions of the Uterine Cervix

The expression of epidermal growth factor receptor (EGF-R), c-erbB-2 proto-oncogene, and estrogen receptor (ER) was studied immunohistochemically in a series of 97 human papillomavirus (HPV) lesions of the uterine cervix, with special emphasis on their association with the HPV type, grade of intraepithelial neoplasia (CIN), and the natural history of the disease. EGF-R expression was found in 95 of 97 (98%) specimens, mainly in basal and parabasal cells. Diffuse nuclear and cytoplasmic staining was detected in 36 of 97 (37%) samples, of which 29 were HPV positive. This staining pattern was most prominent in HPV 18-positive and in CIN lesions. Weak or moderate c-erbB-2 expression was found in 26 of 97 (27%) specimens. Estrogen receptor expression was observed in 28 of 77 (36%) samples, epithelial staining was seen in 11 of 77 (14%), and stromal staining occurred in 24 of 77 (31%) specimens. No clear-cut associations were established between the EGF-R, c-erbB-2, or ER expression and HPV type, nor in CIN or the clinical course of HPV infections. This failure for EGF-R, c-erbB-2, and ER to be associated with the specific HPV types, grade of CIN, or the clinical course of cervical HPV lesions suggests that the assessment of these factors is of limited value in explaining the development of HPV-associated CIN and in predicting the prognosis of this disease.

Classification of Human Papillomavirus Infection

To the Editor. —Infection with oncogenic strains of human papillomavirus (HPV) constitutes a major risk factor for development of precancerous neoplastic lesions and/or cancer of the cervix.1The inability to culture HPV and the lack of reliable serologic tests have hindered characterization of the life cycle and the natural course of HPV infection.2 The use of imprecise terminology that implies a knowledge of the stage of HPV infection is common in the medical literature. For instance, the termlatenthas been used to refer to individuals who have only molecular biological evidence of infection. However, epidemiologists refer to thelatent periodof a disease as the interval between disease onset and detection.3Indeed, individuals who have HPV DNA but no other evidence of infection may be in this early stage of disease. On the other hand, virologists refer to latent viral infections as a state of persistent

Incidence of antibodies to human papillomavirus type 1 in patients with cutaneous and mucosal papillomas

A study of antibodies to human papillomavirus (HPV) 1 is reported in a series of sera from 126 patients with papilloma lesions of different clinical types (verruca plantaris, vulgaris, plana, condyloma acuminata, laryngeal papilloma) using a sensitive solid-phase enzyme-linked immunosorbent assay (ELISA). Our findings showed a significant prevalence of specific HPV 1 IgG antibodies in patients with plantar warts (65%). This incidence was considerably lower in patients with other papilloma lesions, in which positive sera may reflect a past infection with HPV 1. The ELISA test was evaluated as nearly 100 times more sensitive than the indirect immunofluorescence test, and IgG titers to HPV 1 in patients' sera were usually low. Serum samples taken at different times during the course of HPV infection in a few patients with refractory lesions did not show any significant change in their antibody titer.