Evolution of human papilloma virus prevalence in a highly vaccinated region in Belgium: a retrospective cohort study in Flemish women (2010-2019).

OBJECTIVE: In order to lower the incidence of cervical cancer, vaccines against high-risk types of the human papilloma virus (hrHPV) were approved and brought on the market in 2007, with a partial reimbursement for Belgian citizens younger than 18 years old. Since 2010, a school-based vaccination program ensures a high vaccination coverage in young women. In this study, the impact of the Belgian vaccination program on the prevalence of HPV 16/18 is studied, together with the evolution of the prevalence of other hrHPV types and precancerous lesions. METHODS: Results of HPV typing and cytology in papanicolaou-smears from women aged 20-23 years taken between 2010 and 2019 were used. An older, nonvaccinated group of women of 40-45 years old served as a control group. RESULTS: A significant decrease in prevalence of HPV types 16 and 18 was found in the 20-23-years-old women, whereas no decrease was found in the age group 40-45. Alongside this decrease, a significant decrease in prevalence of subtypes 6, 11 and 31 was observed, whereas type 31 is not included in the administered vaccines. Remarkably, there was no decrease in prevalence of cytological abnormalities in the study group during this study. There was even an increase in prevalence of high-risk types 53, 58 and 67. CONCLUSION: These findings emphasise the need to maintain the screening programs, even in areas with high vaccination coverage.

Oral and oropharyngeal high-risk HPV prevalence, HIV status, and risk behaviours in a cohort of South African men who have sex with men.

Data lag is evident when observing studies focussing on human papillomavirus (HPV) prevalence in the head and neck of men who have sex with men (MSM) in Southern Africa. Sexual behaviours other than anal intercourse, and associated factors are similarly underreported. HPV vaccination has not yet commenced for this population group. One hundred and ninety-nine MSM were enrolled in this study. Participants completed a questionnaire followed by a clinical oral examination, and a rinse-and-gargle specimen in Thinprep® vials containing Preservcyt® solution was collected. Detection and genotyping for high-risk HPV were done by an automated system (Abbott® m2000sp). Six percent of MSM in this cohort had high-risk HPV present in the mouth/oropharynx. This cohort averages 29 years of age, more than half were unemployed (53.3%), and 66.8% were human immunodeficiency virus (HIV) seropositive. The most common sexual practice was anal sex (69.4%) followed by oral sex (28.6%), and by rimming (9.6%). A significant association between oral insertive sex and oral/oropharyngeal HPV status was demonstrated (p = 0.0038; phi coefficient = 0.20). An incidental but significant association between rimming and HIV status was found (p = 0.0046; phi coefficient = 0.19), and HIV seropositive participants had higher oral/oropharyngeal HPV presence. The HPV prevalence of 6% reported in this study is in alignment with global reports. The prevalence of oral/oropharyngeal HPV in this MSM cohort was influenced by sexual practices. MSM participants who practiced rimming appear to be at higher risk of HIV acquisition. Given the transmission routes of HPV in this vulnerable population, vaccination must be urgently studied as an intervention for prevention.

Safety evaluation of long-term temperature controlled whole-body thermal treatment in female Aachen minipig.

Objective: Thermal treatment (TT), defined as treatment using supra-physiological body temperatures (39-45 C), somewhat resembles fever in terms of temperature range, one of the first natural barriers for the body to fight exposure to external pathogens. Methods: Whole-body thermal treatment (WBTT) consists of heating up the complete body to a temperature range of 39 to 45 C. Despite the recognized therapeutic potential of hyperthermia, the broad clinical use of WBTT has been limited by safety issues related to medical devices and procedures used to achieve WBTT, in particular adequate control of the body temperature. To circumvent this, a sophisticated medical device was developed, allowing long-term temperature controlled WBTT (41.5 C for up to 8 h). Technical feasibility and tolerability of the WBTT procedure (including complete anesthesia) were tested using female Aachen minipig. Optical fiber temperature sensors inserted in multiple organs were used and demonstrated consistent monitoring and control of different organs temperature over an extended period of time. Results: Clinical evaluation of the animals before, during and after treatment revealed minor clinical parameter changes, but all of them were clinically acceptable. These changes were limited and reversible, and the animals remained healthy throughout the whole procedure and follow-up. In addition, histopathological analysis of selected key organs showed no thermal treatment-related changes. Conclusion: It was concluded that WBTT (41.5 C for up to 8 h) was well tolerated and safe in female Aachen minipigs. Altogether, data supports the safe clinical use of the WBTT medical device and protocol, enabling its implementation into human patients suffering from life-threatening diseases.

Performance of OncoE6TM Cervical Test in detecting cervical precancer lesions in HIV-positive women attending an HIV clinic in Bujumbura, Burundi: a cross-sectional study.

OBJECTIVE: New rapid and low-cost molecular tests for cervical cancer screening, such as the OncoE6 Cervical Test, are emerging and could be alternatives for low-income and middle-income countries. To this end, we evaluated the clinical performance of the OncoE6 Cervical Test in detecting cervical intraepithelial neoplasia (CIN) among HIV-infected women in Bujumbura, Burundi. METHODS: From June to December 2017, a cross-sectional study was conducted in 680 HIV-positive women at the University Hospital. Women aged 25-65 years who declared having had vaginal intercourse were consecutively recruited, and cervical specimens for OncoE6, liquid-based cytology and human papillomavirus (HPV) genotyping were obtained and visual inspection with acetic acid performed. Thereafter, participants underwent a colposcopic examination. The sensitivity, specificity, and positive and negative predictive values of the different tests were calculated with reference to 'colposcopic-histological' diagnoses, and areas under the receiver operating curves of OncoE6 and cytology tests were compared. RESULTS: The prevalence of CIN was 4.9%, and OncoE6 positivity was 3.1%. OncoE6 sensitivity varied from poor to low with increasing disease severity (42.1%, 95% CI 19.9% to 64.3% at CIN2+ threshold; and 58.3%, 95% CI 30.4% to 86.2% at CIN3+ threshold). OncoE6 had the highest specificity compared with all other tests used together. The performance of the OncoE6 test was significantly lower compared with cytology at atypical squamous cell of undetermined significance (ASCUS+) cut-off (AUC=0.68 vs 0.85, p=0.03) and low-grade squamous intraepithelial lesion (LSIL+) cut-off (AUC=0.68 vs 0.83, p=0.04) for CIN2+ diagnoses. However, the performance of the OncoE6 test was similar to that of cytology at high-grade squamous intraepithelial lesion (HSIL+) cut-off (AUC=0.68 vs 0.76; p=0.30) for CIN2+ diagnoses and was also similar to that of cytology at all cut-offs (ASCUS+, LSIL+ and HSIL+) for CIN3+ diagnoses (p1=0.76, p2=0.95 and p3=0.50, respectively). CONCLUSION: The current OncoE6 test proved to be a point-of-care test. However, given its poor performance for CIN2+ diagnoses, we do not recommend it for primary screening. We recommend to enrich it with more oncogenic HPV types, which may improve the performance of the test akin to that of cytology.

Tobacco use and oral sex practice among dental clinic attendees.

Tobacco use and oral sex (OS) are important risk factors for oral and oropharyngeal Human papillomavirus (HPV) infection. Little is known about the prevalence of OS practice in South Africa. This study aimed to determine the prevalence of OS practice and tobacco use in a South African patient population. This cross-sectional study used a structured questionnaire to collect socio-demographic characteristics, tobacco use, betel nut use and OS practice data from consenting adults (≥18 years; n = 850). Oral sex practices were recorded for patients 18-45 years-old (n = 514). Data analysis included chi-square and multiple logistic regression analyses. Of the study population, 55.2% (n = 468) were female, 88% (n = 748) self-identified as black Africans and 45.1% (n = 383) were unemployed. Furthermore, 19.7% (n = 167), 6.4% (n = 54) and 2.1% (n = 18) were current smokers, snuff users and betel nut users, respectively. Out of the 514 who answered the questionnaire in relation to OS, 22.8% (n = 115) reported to practice it. Oral sex practice in the age group 18-45 years was most common among the self-identified white participants (41.9%); and among tobacco users than among non-tobacco users (30.9% vs. 20.5%; p = 0.022). A multivariable-adjusted regression model showed that white South Africans were more likely to use tobacco than black Africans (OR = 5.25; 95% CI = 2.21-12.47). The practice of OS was more likely among those 18-35 years-old (OR = 1.67; 95% CI = 1.01-2.74), but had no significant association with tobacco use (OR = 1.06; 95% CI = 0.62-1.83). The observed age and ethnic differences in both risk behaviours suggest a need for targeted population intervention in order to reduce the risk for oral HPV infection.

Knowledge and practices of general practitioners at district hospitals towards cervical cancer prevention in Burundi, 2015: a cross-sectional study.

BACKGROUND: Well-organized screening and treatment programmes are effective to prevent Invasive Cervical Cancer (ICC) in LMICs. To achieve this, the World Health Organization (WHO) recommends the involvement of existing health personnel in casu doctors, nurses, midwives in ICC prevention. A necessary precondition is that health personnel have appropriate knowledge about ICC. Therefore, to inform policy makers and training institutions in Burundi, we documented the knowledge and practices of general practitioners (GPs) at district hospital level towards ICC control. METHODS: A descriptive cross-sectional survey was conducted from February to April, 2015 among all GPs working in government district hospitals. A structured questionnaire and a scoring system were used to assess knowledge and practices of GPs. RESULTS: The participation rate was 58.2%. Majority of GPs (76.3%) had appropriate knowledge (score > 70%) on cervical cancer disease; but some risk factors were less well known as smoking and the 2 most important oncogenic HPV. Only 8.4% of the participants had appropriate knowledge on ICC prevention: 55% of the participants were aware that HPV vaccination exists and 48.1% knew cryotherapy as a treatment method for CIN. Further, 15.3% was aware of VIA as a screening method. The majority of the participants (87%) never or rarely propose screening tests to their clients. Only 2 participants (1.5%) have already performed VIA/VILI. Wrong thoughts were also reported: 39.7% thought that CIN could be treated with radiotherapy; 3.1% thought that X-ray is a screening method. CONCLUSION: In this comprehensive assessment, we observed that Burundian GPs have a very low knowledge level about ICC prevention, screening and treatment. Suboptimal practices and wrong thoughts related to ICC screening and treatments have also been documented. We therefore recommend an adequate pre- and in-service training of GPs and most probably nurses on ICC control before setting up any public health intervention on ICC control.

Genital Tract Infections in an Isolated Community: 100 Women of the Príncipe Island.

Objective: To characterize the vaginal microbiome and the rate of sexually transmitted infections (STIs) in the women of Príncipe (São Tomé and Príncipe). Methods: Cross-sectional study of 100 consecutive women, invited for a free appointment and cervical cancer screening. A vaginal slide (wet mount microscopy) and a cervical sample (ThinPrep®) (Pap test, high risk human papillomavirus [HR-HPV], N. gonorrhea [NG], T. vaginalis [TV], and C. trachomatis [CT]) were obtained. Results: TV, NG, CT, and HIV were found in 8.0%, 2.0%, 3.0%, and 2.0%, respectively, and were more prevalent in younger women. HR-HPV was positive in 36.7%; 2 were positive for HPV18, but none for HPV16. Coinfection of HPV with other STIs was 8.3%. Prevalence of abnormal vaginal flora (AVF) was 82.5%, mostly bacterial vaginosis (BV) 54.6%, and moderate/severe aerobic vaginitis (msAV) 25.8%. HR-HPV was not related to BV (p = 0.67). The association of abnormal Pap test with msAV was not significant (p = 0.08). Conclusion: The prevalence of NG, CT, TV, and HR-HPV was according to expected, while that of HR-AVF was higher. The surprisingly low prevalence of HPV16 and HPV18 must be considered in the design of programs for prevention and vaccination; this setting can be useful as a model for postvaccination scenarios.

The influence of physical activity in the anti-tumor immune response in experimental breast tumor.

This study aimed to investigate the influence of physical activity in innate immunity to conduce to an effective antitumoral immune response analyzing the phenotype and activation status of infiltrating cells. We analysed the intracellular cytokines and the transcription factors of tumor infiltrating lymphocytes (TILS) and spleen leukocytes. The Nos2 gene expression was evaluated in spleen cells and futhermore the ROS production was measured and spleen cells; another cell evaluated was dendritic cells (TIDCs), their cytokines expression and membrane molecules; finally to understood the results obtained, we analysed the dendritic cells obtained from bone marrow. Were used female Balb/c mice divided into 4 groups: two controls without tumor, sedentary (GI) and trained (GII) and two groups with tumor, sedentary (GIII) or trained (GIV). The physical activity (PA) was realized acoording swimming protocol. Tumor was induced by injection of 4T1 cells. All experiments were performed in biological triplicate. After the experimental period, the tumor was removed and the cells were identified by flow cytometry with labeling to CD4, CD8, CD11c, CD11b, CD80, CD86 and Ia, and intracelular staining IL-10, IL-12, TNF-α, IFN-γ, IL-17, Tbet, GATA3, RORγt and FoxP3. The bone marrow of the animals was obtained to analyse the derivated DCs by flow cytometry and culture cells to obtain the supernatant to measure the cytokines. Our results demonstrated that the PA inhibit the tumoral growth although not to change the number of TILS, but reduced expression of GATA-3, ROR-γT, related with poor prognosis, and TNF-α intracellular; however occur one significantly reduction in TIDCS, but these cells expressed more co-stimulatory and presentation molecules. Furthermore, we observed that the induced PA stimulated the gene expression of Tbet and the production of inflammatory cytokines suggesting an increase of Th1 systemic response. The results evaluating the systemic influence in DCs showed that the PA improve significantly the number of those cells in bone marrow as well the number of co-stimulatory molecules. Therefore, we could conclude that PA influence the innate immunity by interfering to promote in process of maturation of DCs both in tumor and systemically, that by its turn promote a modification in acquired immune cells, representing by T helper to induce an important alteration transcription factors that are responsible to maintain a suppressive microenviroment, and thereby, allowing the latter cells can thus activate antitumor immune response. The PA was able improve the Th1 systemic response by enhance to Tbet gene expression, promote a slightly increased of Th1-type cytokines and decrease Gata3 and Foxp3 gene expression in which can inhibit the Th1 immune response.

On the connection between the tympanic membrane and the malleus.

BACKGROUND: The tympano-mallear connection (TMC) is the soft-tissue connection between the tympanic membrane (TM) and the manubrium of the malleus. Some studies suggest that its mechanical properties may have a substantial influence on the mechanics and transfer function of the middle ear. However, relatively little is known about the dimensions of the TMC and its variability among individuals. METHOD: Thirteen samples were collected from human temporal bones, consisting of only the malleus and the TM. They were imaged using µCT without contrast enhancing agent. From the µCT images, the TMC dimensions were measured in both anterior-posterior direction (TMC width) and medial-lateral direction (TMC thickness). Three selected samples were examined using histological microscopy. RESULTS: Both TMC width and thickness featured a large variability among individuals. The minimal TMC width along the manubrium for different individuals covered a range between 83 and 840 µm. The minimal thickness ranged from 48 to 249 µm and the maximal thickness from 236 to 691 µm. Histological sections showed that the TMC consists of a narrow core of dense regular connective tissue, surrounded by loose connective tissue. In some samples, either of these two components was absent in the TMC at some manubrium locations. The configuration of these components varied among the samples as well. CONCLUSION: Our data confirm that a large inter-individual variability exists in the properties of the TM-malleus connection in humans in terms of its dimensions, tissue composition and configuration. Average data and their variability margins will be useful input for testing the importance of the TMC in finite element models.

Human Papillomavirus Positivity in Women Undergoing Intrauterine Insemination Has a Negative Effect on Pregnancy Rates.

BACKGROUND: Sexually transmitted infections are a major cause of infertility. Human papillomavirus (HPV) infection is one of the most common viral infections of the female genital tract. Only a limited number of studies have investigated the influence of HPV on fertility and its impact remains controversial. OBJECTIVE: We investigated the relationship between cervical HPV infection and pregnancy outcome after intrauterine insemination (IUI). Since other sexually transmitted infections could also influence outcome, we also analyzed the influence of Trichomonas vaginalis (TV) and Chlamydia trachomatis (CT) on pregnancy outcome. METHODS: We performed a retrospective analysis of 590 women who underwent 1,529 IUI cycles at AML between 2010 and 2014. Positivity of 18 different HPV types (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68) and TV was assessed by PCR in cervical cytology specimens. CT status was ascertained by detection of IgA/IgG antibodies on serum samples or by PCR on cervical swabs. RESULTS: The HPV prevalence per IUI cycle was 11.0 and 6.9% for CT; none of the women tested positive for TV. HPV-positive women were six times less likely to become pregnant after IUI (1.87 vs. 11.36%; p = 0.0041). There was no significant difference in pregnancy rates between women with or without a history of CT (8.51 vs. 11.10%; p > 0.05). CONCLUSION: Detection of HPV is associated with a negative IUI outcome.

Angiogenesis Markers in Gynecological Tumors and Patents for Anti-Angiogenic Approach: Review.

The formation of a tumor-associated vascular network is an important step in understanding the stages of tumor progression. This review aims to highlight the main markers of induction, proliferation and inhibition of angiogenesis, as well as the quantification of microvessel density, correlated with preclinical and clinical research in gynecologic cancers and also discussed related patents. Studies show that in the most advanced cases of gynecological cancers, biomarkers such as VEGF (Vascular Endothelial Growth Factor), MMP (Matrix Metalloproteinase), CD105 (Endoglin), TIMP (tissue inhibitors of metalloproteinases) and VASH (Vasohibin) are more expressed compared to healthy individuals. Continuous evaluation of these biomarkers in cancer cases could serve in the future as a basis for development of new therapeutic approaches, leading to a good response to cancer treatment, and thus increase survival of cancer patients.

Laser micro-dissection and qPCR for identifying specific HPV types responsible for malignancy in penile lesions.

The aim of the study was to identify specific human papillomavirus (HPV) type responsible for malignancy in penile tissue samples using laser micro-dissection and TaqMan quantitative real-time PCR (qPCR). The study was based on two pre-malignant and seven malignant penile tissue samples and laser micro-dissection was performed on all. Genotyping was performed on whole tissue sections and laser micro-dissection samples using qPCR. Two whole tissue section samples were HPV negative while seven were HPV positive. In four samples that were single HPV infections with whole tissue section PCR, identical HPV types were confirmed with laser micro-dissection PCR. Clearly confirming that the single HPV type detected is responsible for malignancy. In two samples that had multiple HPV infections with whole tissue section PCR, only one HPV type with the highest viral load was detected with laser micro-dissection PCR, suggesting that the HPV type with the highest viral load is most likely the cause of that particular lesion. HPV 11 and/or HPV 16 were the only types detected with laser micro-dissection PCR in these cases, compared to multiple HPV types (HPV 11, HPV 16, HPV 18, HPV 31, HPV 33, HPV 35, and HPV 39) initially detected with whole tissue section PCR. HPV 11 was associated with verrucous lesions while HPV 16 was associated with squamous cell carcinoma and PIN 3 lesions. This study confirms that laser micro-dissection and qPCR are essential tools in identifying the HPV types responsible for malignancy in penile lesions, particularly in samples with multiple infections.

A murine model of lung ischemia and reperfusion injury: tricks of the trade.

BACKGROUND: Pulmonary ischemia-reperfusion injury (IRI) causes postoperative morbidity in patients undergoing lung transplantation, isolated lung perfusion, and cardiopulmonary bypass and may lead to potentially lethal pathologies such as respiratory shock. In-depth study of this pathology requires a reliable animal model. Mice are a popular species to develop experimental models because of their logistic advantages and the availability of knock outs. However, their small size warrants microsurgical techniques and a skilled surgeon. MATERIALS AND METHODS: We developed a murine model of pulmonary anoxic IRI through hilar clamping using adult female Swiss mice. After left thoracotomy, we expose the pulmonary hilum keeping the ribs and the muscles of back and forepaw intact. A microvascular clamp is placed over the entire hilum, occluding bronchus, pulmonary artery, and vein. RESULTS: Our model proved to be simple, reliable, and reproducible, showing minimal preoperative and postoperative mortality. Histopathologic analysis indicated all characteristic features of pulmonary IRI, such as an early recruitment of lymphocytes followed by neutrophil influx. CONCLUSIONS: This article presents a murine surgery model for pulmonary IRI based on a muscle-sparing thoracotomy. The minimal approach limits manipulation of lung tissue, minimizing mortality and non-IRI-induced injury.

Diversity of HPV types in cancerous and pre-cancerous penile lesions of South African men: implications for future HPV vaccination strategies.

This study reports the detection of HPV types from cancerous and pre-cancerous penile lesions that were diagnosed histologically. Sixty-six (22 pre-cancerous and 44 cancerous lesions) tissue biopsies, received between 2004 and 2011 by the Anatomical Pathology Department at Dr. George Mukhari Hospital were selected for this study. Total DNA was extracted and genotyped using type specific real-time quantitative polymerase chain reaction (qPCR) for 18 HPV types. Of 66 samples, only 51 were included in the analysis. Overall, HPV 11 (50.9%) and HPV 16 (49.1%) showed almost similar incidence in the study patients. In pre-cancerous lesions, HPV 11 was more frequent (80.0%), followed by HPV 31 and HPV 16 at 25.0% each and other HPV types included 35 (15.0%), 59 (15.0%), 53 (10.0%), 33 (10.0%), 18 (5.0%), 51 (5.0%), 52 (5.0%), 56 (5.0%), and 67 (5.0%). For cancerous lesions, HPV 16 was the most detected (62.9%), followed by HPV 11 (34.3%), and other HPV types included 18 (11.4%), 33 (5.7%), 39 (5.7%), 45 (5.7%), 66 (5.7%), 52 (2.9%), 58 (2.9%), 6 (2.9%), and 67 (2.9%). Several lesions demonstrated multiple HPV infections, ranging from two to six different types in one lesion. The study showed high diversity of HPV types in cancerous and pre-cancerous lesions of South African males with the most frequent being HPV types 11 and 16. The data suggest that boys could directly benefit from vaccination as they are exposed to variety of HPV types as early as 10 years of age in Africa.

Probiotics enhance the clearance of human papillomavirus-related cervical lesions: a prospective controlled pilot study.

Probiotics have been proposed for a number of urogenital infectious conditions. In this study, we examine a possible effect on human papillomavirus (HPV)-related precancerous lesions in cervical cytology. We conducted a prospective controlled pilot study, in which 54 women with an HPV+low-grade squamous intraepithelial lesion diagnosis in their PAP smear were followed for 6 months. The intervention group consumed a daily probiotic drink during the study period; the control group received no treatment, according to common care policy. Outcome measures were the control PAP smear and HPV status after 6 months. Probiotic users had a twice as high chance of clearance of cytological abnormalities (60 vs. 31%, P=0.05). HPV was cleared in 19% of control patients versus 29% of probiotic users (P=0.41). This exploratory pilot study suggests that the probiotic studied promotes the clearance of HPV-related cytological abnormalities. If confirmed, this would represent an entirely new option to manage cervical cancer precursors.

Association of Trichomonas vaginalis and cytological abnormalities of the cervix in low risk women.

OBJECTIVE: Is Trichomonas vaginalis (TV) an inducing factor for the development of (pre-)cancerous lesions of the cervix? DESIGN: Cross sectional study. SETTING: Screening healthy Belgian women with low infection risk. SAMPLE: 63,251 consecutive liquid based cervical samples. METHODS: Real time quantitative PCR for presence of TV, 18 HPV types and Pap smear analysis of cytologic abnormalities. MAIN OUTCOME MEASURES: Association of TV and HPV with cervix dysplasia. RESULTS: The overall prevalence of TV DNA was 0.37%, of low risk HPV 2%, of high risk HPV 13.2%, and 8.8 % had cytological abnormalities. Both LR-HPV and HR-HPV were significantly associated with all cytological abnormalities. Presence of TV was associated with LR- and HR-HPV, ASC-US and HSIL, but not with other abnormalities. All women with TV and HSIL also had HR-HPV, while the latter was present in only 59% of women with TV and ASC-US. Amongst HPV negative women, TV was found in 1.3% of women with ASC-US, but only in 0.03% of women with normal cytology (OR 4.2, CL95% 2.1-8.6). In HR-HPV positive women, presence of TV increased the likelihood of cytological abnormalities somewhat (P=0.05), mainly due to an increase in ASC-US and LSIL, but not HSIL. CONCLUSIONS: We conclude that TV infection is associated with both LR and HR-HPV infection of the cervix, as well as with ASC-US and HSIL. TV is a concomitant STI, but is not thought to be a co-factor in the causation of HSIL and cervical cancer. However, TV may cause false positive diagnoses of ASC-US.

Cervical cytology biobanks as a resource for molecular epidemiology.

A cervical cytology biobank (CCB) is an extension of current cytopathology laboratory practice consisting in the systematic storage of Pap smears or liquid-based cytology samples from women participating in cervical cancer screening with the explicit purpose of facilitating future scientific research and quality audit of preventive services. A CCB should use an internationally agreed uniform cytology terminology, be integrated in a national or regional screening registry, and linked to other registries (histology, cancer, and vaccination). Legal and ethical principles concerning personal integrity and data safety must be respected strictly. Biobank-based studies require approval from ethical review boards. A CCB constitutes a nearly inexhaustible resource to perform fundamental and applied biologic research. In particular, it can contribute in answering questions on the natural history of HPV infection and HPV-induced lesions and cancers, screening effectiveness, exploration of new biomarkers, and surveillance of short- and long-term effects of the introduction of HPV vaccination. To understand the limitations of CCB, more studies are needed on quality of samples in relation to sample type, storage procedures, and duration of storage.

Association of HIV infection with distribution and viral load of HPV types in Kenya: a survey with 820 female sex workers.

BACKGROUND: Human papillomavirus (HPV) and HIV are each responsible for a considerable burden of disease. Interactions between these infections pose substantial public health challenges, especially where HIV prevalence is high and HPV vaccine coverage low. METHODS: Between July 2005 and January 2006, a cross-sectional community-based survey in Mombasa, Kenya, enrolled female sex workers using snowball sampling. After interview and a gynaecological examination, blood and cervical cytology samples were taken. Quantitative real-time PCR detected HPV types and viral load measures. Prevalence of high-risk HPV was compared between HIV-infected and -uninfected women, and in women with abnormal cervical cytology, measured using conventional Pap smears. RESULTS: Median age of the 820 participants was 28 years (inter-quartile range [IQR] = 24-36 years). One third of women were HIV infected (283/803; 35.2%) and these women were y more likely to have abnormal cervical cytology than HIV-negative women (27%, 73/269, versus 8%, 42/503; P < 0.001). Of HIV-infected women, 73.3% had high-risk HPV (200/273) and 35.5% had HPV 16 and/or 18 (97/273). Corresponding figures for HIV-negative women were 45.5% (229/503) and 15.7% (79/503). After adjusting for age, number of children and condom use, high-risk HPV was 3.6 fold more common in HIV-infected women (95%CI = 2.6-5.1). Prevalence of all 15 of the high-risk HPV types measured was higher among HIV-infected women, between 1.4 and 5.5 fold. Median total HPV viral load was 881 copies/cell in HIV-infected women (IQR = 33-12,110 copies/cell) and 48 copies/cell in HIV-uninfected women (IQR = 6-756 copies/cell; P < 0.001). HPV 16 and/or HPV 18 were identified in 42.7% of LSIL (32/75) and 42.3% of HSIL (11/26) lesions (P = 0.98). High-risk HPV types other than 16 and 18 were common in LSIL (74.7%; 56/75) and HSIL (84.6%; 22/26); even higher among HIV-infected women. CONCLUSIONS: HIV-infected sex workers had almost four-fold higher prevalence of high-risk HPV, raised viral load and more precancerous lesions. HPV 16 and HPV 18, preventable with current vaccines, were associated with cervical disease, though other high-risk types were commoner. HIV-infected sex workers likely contribute disproportionately to HPV transmission dynamics in the general population. Current efforts to prevent HIV and HPV are inadequate. New interventions are required and improved implementation of existing strategies.

Mechanisms of cell entry by human papillomaviruses: an overview.

As the primary etiological agents of cervical cancer, human papillomaviruses (HPVs) must deliver their genetic material into the nucleus of the target cell. The viral capsid has evolved to fulfil various roles that are critical to establish viral infection. The particle interacts with the cell surface via interaction of the major capsid protein, L1, with heparan sulfate proteoglycans. Moreover, accumulating evidence suggests the involvement of a secondary receptor and a possible role for the minor capsid protein, L2, in cell surface interactions.The entry of HPV in vitro is initiated by binding to a cell surface receptor in contrast to the in vivo situation where the basement membrane has recently been identified as the primary site of virus binding. Binding of HPV triggers conformational changes, which affect both capsid proteins L1 and L2, and such changes are a prerequisite for interaction with the elusive uptake receptor. Most HPV types that have been examined, appear to enter the cell via a clathrin-dependent endocytic mechanism, although many data are inconclusive and inconsistent. Furthermore, the productive entry of HPV is a process that occurs slowly and asynchronously and it is characterised by an unusually extended residence on the cell surface.Despite the significant advances and the emergence of a general picture of the infectious HPV entry pathway, many details remain to be clarified. The impressive technological progress in HPV virion analysis achieved over the past decade, in addition to the improvements in general methodologies for studying viral infections, provide reasons to be optimistic about further advancement of this field.This mini review is intended to provide a concise overview of the literature in HPV virion/host cell interactions and the consequences for endocytosis.

Urine versus brushed samples in human papillomavirus screening: study in both genders.

AIM: To investigate whether urine is a good medium for screening and whether there is a correlation between the amount of extracted DNA and human papillomavirus (HPV)-positivity. METHODS: In the present study, 30 first-voided urine (FVU) specimens and 20 urethroglandular swabs using cervex-brushes from male partners of HPV-positive patients, and 31 FVU specimens and 100 liquid-based cervix cytology leftovers sampled with cervix-brushes from HPV-positive women were examined for the presence of beta-globin. Oncogenic HPV were detected using type-specific PCR. RESULTS: beta-globin was found in all the brushed samples, whereas it was found in only 68.9% of the FVU specimens. HPV-PCR was positive in 60.0% of the male brushes, in 29% of the female brushes and in 0% of the male FVU specimens. DNA concentration was, respectively, 0.9998 ng/microL, 37.0598 ng/microL and 0.0207 ng/microL. CONCLUSION: Urine is not a good tool for HPV detection, probably because the low DNA concentration reflects a low amount of collected cells. beta-globin is measurable in FVU by real time quantitative PCR, but the DNA concentration is lower compared to brush sampling for both genders. beta-globin-positivity of urethral and cervical swabs is 100%, showing a higher mean concentration of DNA, leading to a higher detection rate of HPV. This is the first article linking DNA-concentration to the presence of HPV.