HPV-infected Women Research Articles

Incidence, Persistence, and Determinants of Human Papillomavirus: A Prospective Cohort Study of HIV-Negative Nigerian Women

Abstract 63 Background: Cervical cancer is the second most common cancer in Africa. Persistent high-risk human papillomavirus (HRHPV) infection is a necessary cause but little is known about the persistence and associated risk factors of HRHPV infection in African women. We undertook this work to determine risk factors and the incidence of HPV infection in Nigerian women. Methods: ACCME is a multicenter, prospective cohort study of host germline, cervical somatic and HRHPV genomics, epigenomics, and vaginal microenvironment and their association with HPV. From February 2014 to January 2016, 10,000 HIV-negative women were enrolled in the cohort and are being observed every 6 months. We used SPF25/LiPA10 to characterize HPV infection and defined persistent infection as two consecutive positive tests performed at least 12 months apart. Logistic regression models were used to estimate associations between risk factors and persistent HPV. Results: The mean (± standard deviation) age of study participants at baseline was 40 (± 10) years, and mean (± standard deviation) vaginal pH was 5.2 (± 0.6). Approximately 42% of participants were positive for any HPV and 21% had persistence of any HPV infection. Some (35%) participants had multiple infections with any HPV. Approximately 54% of those with persistent any HPV infection had HRHPV—HPV type 52 (25%) and type 18 (15%) were the most prevalent and persistent HRHPV types. Incidence of any HPV infection was 6.6 per 1,000 person-months, whereas that of HRHPV was 2.6 per 1,000 person-months. Age, body mass index, education level, marital and socioeconomic status, and total number of lifetime sexual partners were associated with HPV infection in these women. Conclusion: We defined the incidence, risk factors, and most common types of HRHPV in a large cohort of women in West Africa. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Sally N. Adebamowo No relationship to disclose Michael Odutola No relationship to disclose Ayotunde Famooto No relationship to disclose Eileen Dareng No relationship to disclose Amos Adebayo No relationship to disclose Peter Achara No relationship to disclose Bunmi Alabi No relationship to disclose Kayode Obende No relationship to disclose Richard Offiong No relationship to disclose Sanni Ologun No relationship to disclose Clement A. Adebamowo Speakers' Bureau: Merck

Evaluation of expression of the cell adhesion marker at cervical intraepithelial neoplasia depending on the type infertility.

Background. One of the most frequent malignant neoplasms of the reproductive system of women is cervical cancer. Cervical intraepithelial neoplasia represents one of the stage of malignisation of cervical epithelium. The number of studies aimed at investigation the E-cadherin as neoplastic progression indicator in cervical tissue at CIN is not a lot, and the findings are mixed. Also, there are no data on the level of expression of E-cadherin and load of human papilloma virus with high carcinogenic risk. Objective. Was conducted immunohistochemical study of the expression of the cell adhesion marker E-cadherin at CIN that are associated with HPV infection in women with infertility. Methods. Was investigated 236 cervical biopsies from women with infertility and in the 157 cases in the cervical smears identified the human papillomavirus types with high carcinogenic risk by polymerase chain reaction. In the immunohistochemical study as a primary was used monoclonal antibodies to E-cadherin (clone ER700Y, LabVision). During assessing the immunohistochemical reactions with E-cadherin, a membrane and submembranne coloring was considered as specific. The colorating was considered as "typical" if the response was uniform and equal in intensity that characterised normal squamous epithelium without keratinisation. Results. During the CIN that associated with PVI registered decrease up to total loss of expression for the glycoprotein of the membrane adhesion - E-cadherin. In 25 (10.59%) cases is excessive "atypical" mixed cytoplasmic membrane expression of E-cadherin. This type of reaction takes all layers of the mucous membrane of the cervix. The frequency of excessive "atypical" cell adhesion marker expression increases with the level of CIN and viral load. Excessive "atypical" expression of E-cadherin at CIN that associated with HPV infection with the highest rate (60.0%, p <0.05) observed in tubal infertility. Conclusion. The use of the E-cadherin can be introduced in medical practice as an additional criterion concerning the diagnosis and prognosis CIN associated with HPV infection in women with infertility. The use of E-cadherin must ensure objectivity for morphological investigation, especially in dysplastic degree verification process that will improve the quality of examination of patients with this pathology.

The singular epidemiology of HPV infection among French Guianese women with normal cytology

BackgroundIn French Guiana, cervical cancer is the second most frequent cancer in females. The objective of the present study was to describe the prevalence of HPV infections in women with normal cervical cytology living in the remote villages of French Guiana.MethodsBefore the study, the study team communicated in the remote villages on the importance of screening. All women from the target population were offered to participate. They signed informed consent during inclusion and then had a concomitant HPV-test and cervical smear. Only women with normal cytology and a good quality smear were analyzed. The detection of HPV-DNA was performed using the GREINER-BIO-ONE kit.ResultsOverall, 27.2% of women with normal cervical cytology had a positive HPV-test. There was a U-shaped evolution of prevalence with women over 50 years having the highest HPV prevalence, followed by the 20 to 29 years group. The most prevalent HPV genotypes were HPV 53(3.52%), 68(3.33%), 52(2.59%), 31(2.22%) and 16 (1.85%). The proportion of HPV 16 among HPV-infected women was 6.8%.ConclusionsHPV prevalence in cytologically normal women was very high. The most prevalent genotypes were very different from what is usually described in the world, and notably in South America.

The association between adverse pregnancy outcomes and maternal human papillomavirus infection: a systematic review protocol

BackgroundHuman papillomavirus (HPV) is the most prevalent genital infection, especially in young women of reproductive age. In vitro and animal model experiments provide compelling evidence of the harmful effect of HPV on pregnancy outcomes, but results from epidemiologic studies are inconclusive. We aim to determine the strength of the relationship between adverse pregnancy outcomes (APO) and HPV infection and assess its consistency across studies, by systematically reviewing the literature.MethodsThe search strategy has been developed on the basis of the PICOS framework: Population (pregnant women); Exposure (HVP infection confirmed by HPV testing); Comparator (pregnant women without HPV infection); Outcomes (miscarriage, spontaneous preterm birth, low birth weight, preterm premature rupture of membranes, pregnancy-induced hypertensive disorders and intrauterine growth restriction) and Study design (observational studies). We will search three information sources: (1) electronic databases (MEDLINE, EMBASE, and EBM Reviews databases); (2) Grey literature (Google Scholar and Web of Science conference proceedings); and (3) citing and cited articles of included studies. Two reviewers (JN, NZ) will independently and in duplicate screen identified articles, select eligible studies, and extract data. Discrepancies will be resolved by consensus and otherwise by discussion with the other authors (MHM, HT). Quality of included studies will be assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies. We will narratively synthesize extracted data whether meta-analysis is conducted or not. Meta-analysis of each outcome will be performed, and where appropriate, an average measure of association will be computed. We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess and grade the strength of confidence in cumulative estimate.DiscussionComprehensive and high-quality evidence of a negative effect of HPV on pregnancy outcomes might be an additional motivation for HPV vaccination. Absence of such relationship could dispel anxiety and reassure HPV-infected pregnant women and clinicians. Findings of a poor level of confidence will allow identification of current knowledge gaps on HPV-pregnancy outcome relationship that need further research.Systematic review registrationPROSPERO CRD42016033425

Functional association of oestrogen receptors with HPV infection in cervical carcinogenesis.

Repeated parity and usage of oral contraceptives have demonstrated an increased risk of cervical cancer (CC) in HPV-infected women. These lifestyle observations raise the likelihood that oestrogens and HPV infection might act synergistically to affect cancers of the cervix. In vivo studies have indicated the requirement of oestrogens and ERα in the development of atypical squamous metaplasia followed by cervical intraepithelial neoplasia (CIN) I, II and III. CIN II and III are precancerous cervical lesions that can progress over time to CC as an invasive carcinoma. Recently, there has been evidence suggesting that ERα signalling in the tumour epithelium is a preliminary requisite during cancer initiation that is subsequently lost during tumorigenic progression. Conversely, continued expression of stromal ERα gains control over tumour maintenance. This review summarises the current information on the association between oestrogens and HPV infection in contributing to CC and the possibility of SERMs as a therapeutic option.

GTL001 and bivalent CyaA-based therapeutic vaccine strategies against human papillomavirus and other tumor-associated antigens induce effector and memory T-cell responses that inhibit tumor growth

GTL001 is a bivalent therapeutic vaccine containing human papillomavirus (HPV) 16 and HPV18 E7 proteins inserted in the Bordetella pertussis adenylate cyclase (CyaA) vector intended to prevent cervical cancer in HPV-infected women with normal cervical cytology or mild abnormalities. To be effective, therapeutic cervical cancer vaccines should induce both a T cell-mediated effector response against HPV-infected cells and a robust CD8+ T-cell memory response to prevent potential later infection. We examined the ability of GTL001 and related bivalent CyaA-based vaccines to induce, in parallel, effector and memory CD8+ T-cell responses to both vaccine antigens. Intradermal vaccination of C57BL/6 mice with GTL001 adjuvanted with a TLR3 agonist (polyinosinic-polycytidylic acid) or a TLR7 agonist (topical 5% imiquimod cream) induced strong HPV16 E7-specific T-cell responses capable of eradicating HPV16 E7-expressing tumors. Tumor-free mice also had antigen-specific memory T-cell responses that protected them against a subsequent challenge with HPV18 E7-expressing tumor cells. In addition, vaccination with bivalent vaccines containing CyaA-HPV16 E7 and CyaA fused to a tumor-associated antigen (melanoma-specific antigen A3, MAGEA3) or to a non-viral, non-tumor antigen (ovalbumin) eradicated HPV16 E7-expressing tumors and protected against a later challenge with MAGEA3- and ovalbumin-expressing tumor cells, respectively. These results show that CyaA-based bivalent vaccines such as GTL001 can induce both therapeutic and prophylactic anti-tumor T-cell responses. The CyaA platform can be adapted to different antigens and adjuvants, and therefore may be useful for developing other therapeutic vaccines.

Synergic effect of oral contraceptives, GSTP1 polymorphisms, and high-risk HPV infection in development of cervical lesions.

Human papillomavirus (HPV) infection is considered a risk factor for cervical cancer. Even if the high-risk HPV (HR-HPV) infection is necessary, environmental co-factors and genetic susceptibility also play an important role in cervical cancer development. In this study, a possible association of rs1695 GSTP1 polymorphisms, HR-HPV infection, and oral contraceptive use with cancer lesion development in women was investigated. The study population comprised 441 Brazilian women from the Northeast region including 98 HPV-infected women with high-grade squamous intraepithelial lesions, 77 HPV-infected women with low-grade squamous intraepithelial lesions, and 266 HPV-negative women with no lesion, used as a control. Our data did not show a significant association between the GSTP1 polymorphism A/G (rs1695) and any HPV-related cervical abnormalities. However, considering the use of oral contraceptives, the GSTP1 rs1695 polymorphism was associated with higher susceptibility to the development of cervical lesions in HR-HPV-infected women. Our study suggests a synergic effect of oral contraceptive use, GSTP1 polymorphisms, and HR-HPV infection in the development of cervical lesions. Together, these risk factors may induce neoplastic transformation of the cervical squamous epithelium, setting conditions for secondary genetic events leading to cervical cancer.

Relación entre la infección por el virus del papiloma humano y Chlamydia trachomatis

Human papillomavirus (HPV) infection is required but not sufficient to develop cervical cancer, since only a small proportion of HPV-infected women develop cervical intraepithelial lesions or cancer. This leads to the conclusion that other factors are required to facilitate disease progression. According to several studies, Chlamydia trachomatis (CT) infection is more prevalent in HPV-infected women and seems to contribute to the progression of HPV-related epithelial lesions. It is therefore indirectly related to cervical cancer. CT infection screening and the proper treatment of this condition could avoid the consequences of this genital infection (salpingitis, pelvic inflammatory disease, infertility, etc.) and its impact on developing cervical cancer.

Abstract B29: ZNF516 a potential tumor suppressor gene candidate is implied in tumor progression in cervical cancer

Abstract Background: In Cervical Cancer (CC) the role of HPV is fundamental; however, not all HPV infected women will develop this disease. Therefore, other mechanisms, such as silencing of tumor suppressor genes (TSG), could be implied in cervical carcinogenesis. In a previous study, we constructed methylation microarrays, where we found promoter aberrant hypermethylation of ZNF516 gen in CC, postulating it as TSG candidate. The aim of this study was to characterizer ZNF516 role in cervical carcinogenesis and cell cycle. Materials and methods: ECT1 E6/E7 (immortalized normal squamous epithelia cell line) and three CC cell lines: SiHa, C-4I and C-33A were cultivated for experiments. ZNF516 expression was determined by qRT-PCR and western blot. Treatment with 10 μM 5-aza-2′deoxycytidine (5- aza) was performed to evaluate a possible epigenetic regulation. Transfection with pCMV6-ZNF516-GFP (ZNF516) and pCMV6-GFP (Empty) was carried out in C-33A cell line through lipofection followed by G418 selection to obtain stable transfection. Viability and clonogenic assay was performed to evaluate transfected cell behaviour. Also, immnunohistochemical analysis was performed in 509 cervical biopsy tissues (55 normal; 188 low-squamous intraepithelial lesions; 205 high- squamous intraepithelial lesions and 57 squamous cervical cancers). Results: ZNF516 mRNA expression was significantly downregulated in SiHa (p<0.01) and C-33A (p<0.001) respect to ECT1 E6/E7. Western blot showed a deregulated protein expression of ZNF516 in all CC cell lines. After treatment with 5-aza, mRNA (p<0.05) and protein expression of ZNF516 of all CC cell lines were restored. ZNF516 transfected C-33A showed a significant colony formation (p<0.01) and viability (p<0.01) decrease compared with C-33A transfected with the empty vector. Nuclear expression of ZNF516 in cervical biopsies showed a diminished expression in SCC respect to normal epithelia (p<0.001) Conclusions: There is a clear ZNF516 dysregulation in CC cell lines, and the inactivation mechanism seem to be methylation. Restored expression of ZNF516 in C-33A cell line modifies the tumor phenotype, decreasing cellular viability and colony formation. These results suggest that ZNF516 could be a TSG, and its inactivation promotes CC developing. Citation Format: Carmen Gloria Ili, Tamara Viscarra, Juan Carlos Araya, Jaime Lopez, Barbara Mora, Javier Retamal, Enrique Bellolio, Susana Aedo, Juan Carlos Roa, Priscilla Brebi. ZNF516 a potential tumor suppressor gene candidate is implied in tumor progression in cervical cancer. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Cancer Cell Cycle - Tumor Progression and Therapeutic Response; Feb 28-Mar 2, 2016; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(11_Suppl):Abstract nr B29.

Punch biopsy guided by both colposcopy and HR-HPV status is more efficient for identification of immediate high-grade squamous intraepithelial lesion or worse among HPV-infected women with atypical squamous cells of undetermined significance

ObjectivesTo investigate the accuracy of colposcopy for diagnosing high-grade squamous intraepithelial lesion (HSIL) or worse (HSIL+) in human papillomavirus (HPV)-infected patients with atypical squamous cells of undetermined significance (ASCUS) cytology, and determine whether genotyping and viral load quantitation can be useful for detecting immediate HSIL+ risk in these patients. Study designThis study included 620 cases with ASCUS and positive for high-risk (HR)-HPV within 1 month before or after cervical cytology at Qilu Hospital between February 2013 and February 2014. Based on the colposcopic impression, lesion-targeted punch biopsy, endocervical curettage biopsy or random cervical punch biopsy in four quadrants was performed on these patients within 1 month. The accuracy of colposcopy for diagnosing HSIL+ was evaluated through comparison with the biopsy results. HR-HPV status determined by Hybrid Capture 2 or HPV genotyping was analysed retrospectively as a possible predictor of HSIL+. ResultsAgreement between colposcopic impression and cervical pathology was matched perfectly in 89.2% of cases (553/620), and the strength of agreement with the κ statistic was 0.698 (p<0.001). Colposcopy had high specificity (96.9%) but low sensitivity for detecting HSIL+ (67.5%). The risk of HSIL+ was significantly higher in patients with HPV-16 infection (52.3%) than in patients infected with other types of HPV (17.9%, p<0.001). HSIL+ and virus load was correlated at cut-offs (CO) of 50 relative light units (RLU)/CO and 100 RLU/CO (p=0.024 and 0.044, respectively). If considering HPV16 infection or high virus load (at 50 RLU/CO) as a diagnostic standard of HSIL+ when colposcopic impression was negative, sensitivity was improved to 74.7% and 81.0%, respectively. ConclusionsGood agreement was found between colposcopic and pathologic diagnosis. HR-HPV genotyping or virus load is relevant to the detection of HSIL+ among HPV-infected patients with ASCUS cytology. In these patients, biopsies considering HPV-16 infection or virus load ≥50 RLU/CO may be helpful for increasing the HSIL+ detection rate.

Distribution of Vaccine-Type Human Papillomavirus Does Not Differ by Race or Ethnicity Among Unvaccinated Young Women.

Previous studies have demonstrated racial and ethnic differences in the distribution of human papillomavirus (HPV) types among adult women with cervical precancers. The aim of this study was to determine whether the distribution of vaccine-targeted HPV types varies by race/ethnicity among unvaccinated young women. A secondary analysis was performed using data from four studies of sexually experienced, unvaccinated, 13-26-year-old women. Participants completed surveys and provided a cervicovaginal swab for HPV DNA testing. Multivariable logistic regression analyses were performed to examine whether race, ethnicity, and other factors were associated with type-specific HPV infection among the overall sample and among HPV-infected participants. Models controlled for age, HPV knowledge, sexual behaviors, substance use, and random study effect. The mean age of participants (N = 841) was 19.3 years; 64.4% were black and 8.9% Hispanic. Black women were more likely than white women to be positive for ≥1 HPV type (odds ratio [OR] 1.83, 95% CI 1.30-2.58) and Hispanic women were less likely than non-Hispanic women to be positive for ≥1 HPV type (OR 0.47, 95% CI 0.24-0.92). However, among all young women and HPV-infected women, neither race nor ethnicity was associated with positivity for HPV types targeted by the following vaccines: 2-valent (HPV16 and/or 18), 4-valent (HPV6, 11, 16, and/or 18), or 9-valent (HPV6, 11, 16, 18, 31, 33, 45, 52, and/or 58). The prevalence of HPV types targeted by the 2-valent, 4-valent, and 9-valent vaccines did not differ by race or ethnicity among all and among HPV-infected women in this sample.

Molecular analysis of human Papillomavirus detected among women positive for cervical lesions by visual inspection with acetic acid/Lugol's iodine (VIA/VILI) in Libreville, Gabon.

BackgroundThe human papillomavirus (HPV) is the causative agent of cervical cancer, which is the leading cancer-related cause of death for women in Sub-Saharan Africa. In 2013, the Gabonese Ministry of Health and the Sylvia Bongo Ondimba Foundation implemented cervical cancer screening programs based on the detection of cancerous lesions by visual inspection with acetic acid and/or Lugol’s iodine (VIA/VILI). This pilot study was set up to determine the HPV profile and analyze the nucleotide sequence variation of HPV16 circulating in patients with cervical abnormalities detected by VIA/VILI testing.MethodsThe cervical abnormalities observed upon VIA/VILI were confirmed by liquid-based cytology for all tested women. Nested PCR using the MY09/11 and GP5+/6+ primer sets was used to detect HPVs present in the extracted DNA. HPV genotypes were determined after sequencing of amplicons based on a high-throughput sequencing approach. For isolates of the HPV16 genotype, the E6 gene and the long control region (LCR) were directly sequenced using Sanger method.ResultsThe study included 87 women who showed a positive VIA/VILI result. Cervical abnormalities were found in 40.23 % of women and 40 % were classified as high-grade lesions. The HPV detection rate was 82.9 % among women with abnormal cytology. Among all the identified high-risk HPV genotypes, HPV16, 18 and 33 were the most frequent. Multiple HPV infections were observed in 42.31 % of HPV-infected women. Analysis of the HPV16 sequence variation in the E6 gene and in the LCR showed that 85.3 and 14.7 % belonged to the African and European lineages, respectively. Among the African branch variants, Af2 was the most frequently identified in this study.ConclusionThis study offers the first report of the HPV detection rate and molecular epidemiology among Gabonese women with a positive result in a VIA/VILI screening test. Moreover, data on the HPV16 sequence variation confirm the predominance of African variants in high-grade lesions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13027-016-0098-1) contains supplementary material, which is available to authorized users.

TMEM45A, SERPINB5 and p16INK4A transcript levels are predictive for development of high-grade cervical lesions.

Women persistently infected with human papillomavirus (HPV) type 16 are at high risk for development of cervical intraepithelial neoplasia grade 3 or cervical cancer (CIN3+). We aimed to identify biomarkers for progression to CIN3+ in women with persistent HPV16 infection. In this prospective study, 11,088 women aged 20-29 years were enrolled during 1991-1993, and re-invited for a second visit two years later. Cervical cytology samples obtained at both visits were tested for HPV DNA by Hybrid Capture 2 (HC2), and HC2-positive samples were genotyped by INNO-LiPA. The cohort was followed for up to 19 years via a national pathology register. To identify markers for progression to CIN3+, we performed microarray analysis on RNA extracted from cervical swabs of 30 women with persistent HPV16-infection and 11 HPV-negative women. Six genes were selected and validated by quantitative PCR. Three genes were subsequently validated within a different and large group of women from the same cohort. Secondly, Kaplan-Meier and Cox-regression analyses were used to investigate whether expression levels of those three genes predict progression to CIN3+. We found that high transcript levels of TMEM45A, SERPINB5 and p16INK4a at baseline were associated with increased risk of CIN3+ during follow-up. The hazard ratios of CIN3+ per 10-fold increase in baseline expression level were 1.6 (95% CI: 1.1-2.3) for TMEM45A, 1.6 (95% CI: 1.1-2.5) for p16INK4a, and 1.8 (95% CI: 1.2-2.7) for SERPINB5. In conclusion, high mRNA expression levels of TMEM45A, SERPINB5 and p16INK4a were associated with increased risk of CIN3+ in persistently HPV16-infected women.

HPV16 Sublineage Associations With Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women.

HPV16 is a common sexually transmitted infection although few infections lead to cervical precancer/cancer; we cannot distinguish nor mechanistically explain why only certain infections progress. HPV16 can be classified into four main evolutionary-derived variant lineages (A, B, C, D) that have been previously suggested to have varying disease risks. We used a high-throughput HPV16 whole-genome sequencing assay to investigate variant lineage risk among 3215 HPV16-infected women. Using sublineages A1/A2 as the reference, we assessed all variant lineage associations with infection outcome over three or more years of follow-up: 1107 control subjects (<CIN2), 906 CIN2, 1008 CIN3, 69 squamous cell carcinomas (SCC), 85 adenocarcinomas in situ (AIS), and 40 adenocarcinomas. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. A4 sublineage was associated with an increased risk of cancer, specifically adenocarcinoma (OR = 9.81, 95% CI = 2.02 to 47.69, P = 4.7x10(-03)). Lineage B had a lower risk of CIN3 (OR = 0.51, 95% CI = 0. 28 to 0.91, P = 02) while lineage C showed increased risk (OR = 2.06, 95% CI = 1.09 to 3.89, P = 03). D2/D3 sublineages were strongly associated with an increased risk of CIN3 and cancer, particularly D2 (OR for cancer = 28.48, 95% CI = 9.27 to 87.55, P = 5.0x10(-09)). D2 had the strongest increased risk of glandular lesions, AIS (OR = 29.22, 95% CI = 8.94 to 95.51, P = 2.3x10(-08)), and adenocarcinomas (OR = 137.34, 95% CI = 37.21 to 506.88, P = 1.5x10(-13)). Moreover, the risk of precancer and cancer for specific variant lineages varied by a women's race/ethnicity; those women whose race/ethnicity matched that of the infecting HPV16 variant had an increased risk of CIN3 + (P < 001). Specific HPV16 variant sublineages strongly influence risk of histologic types of precancer and cancer, and viral genetic variation may help explain its unique carcinogenic properties.

Prevalence, genotyping, and correlates of anogenital HPV infection in a population-based sample of women in Puerto Rico

BackgroundOncogenic HPV infection is associated to anogenital cancer. We estimate the prevalence and correlates of anogenital HPV infection among a population-based sample of women aged 16–64 years living in the metropolitan area of Puerto Rico. Methods564 women completed face-to-face and computer assisted interviews and self-collected anal and cervical specimens. HPV DNA testing used MY09/MY11 consensus HPV L1 primers and beta-globin as an internal control for sample amplification. Positive specimens were typed by dot-blot hybridization. ResultsWeighted prevalence of cervical, anal, and cervical/anal co-infection was 29.4%, 38.6%, and 17.1%, respectively. The commonest oncogenic HPV types detected in the cervix and anus were: 68 (8% vs. 7%) and 16 (5.5% vs. 5.1%), correspondingly. Having ≥3 lifetime sexual partners (OR: 2.3; 95% CI: 1.5–3.5) and last year anal intercourse (OR: 1.6; 95% CI: 1.1–2.5) increased the odds of anogenital HPV infection. Cervical infection was independently associated to anal infection (OR: 3.0; 95% CI: 2.0–4.6). ConclusionsSimilar to others, our results confirm the burden of anogenital HPV infection in women and its relationship with sexual behavior. As vaccination increases, future studies should monitor changing trends in HPV infection in this population, and the relationship between anal and cervical HPV-related disease.

Safety evaluation of chemically modified beta-lactoglobulin administered intravaginally.

Currently, there is no specific antiviral therapy for treatment of HPV infection. Jiang and colleagues previously reported that anhydride-modified proteins have inhibitory activities against multiple viruses including HPV. Here, we evaluated the safety of 3-hydroxyphthalic anhydride-modified bovine beta-lactoglobulin, designated JB01, vaginally applied in women infected by high-risk HPV. After the vaginal application of JB01 in 38 women for 3 months, no serious adverse events were reported, and normalization of the vaginal micro-environment has been observed. It can be concluded that JB01-BD is safe for vaginal use in HPV-infected women, suggesting its potential application for the treatment of HPV infection.

Relevant Frequency of Multiple Infections with High- and Low-Risk HPV Genotypes among Mexican Women Attending a Tertiary Care Hospital

Aims: To assess the frequency and the main HPV genotypes circulating among a group of women attending at a third level Hospital in Mexico City. Methods: A cross-sectional and descriptive study was performed in a group of 143 female outpatients of the Gynecology and Obstetrics Service at the National Institute of Perinatology of Mexico. Cervical swabs were taken from participants and subjected to simultaneous detection/genotyping of HPV by Linear Array Genotyping Test (Roche Molecular Systems). Mann-Whitney U, median and/or Square Chi tests were used to compare socio-demographical features between HPV-infected and uninfected women. Results: A total of 66 women (46.2%) had HPV infection. Overall, 112 genotypes were detected either as single infections (45.5%) or multiple genotype infections (54.5%). The cumulated frequency of multiple infections with high-/low- and high-/high-risk HPV genotypes was 63.9 %. The most frequent high-risk genotypes were HPV52 HPV58 and HPV51, whereas the most frequent low-risk genotypes were HPV6, HPV53 and HPV84. Infected women were significantly younger and have less stable partner relationships than uninfected women (p < 0.05). Conclusion: A relevant frequency of mixed infections with high- and low-risk HPV genotypes, other than those considered most prevalent worldwide, was observed. Most circulating high-risk genotypes among the women of this study are not covered by commercial vaccine formulations.

Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women.

Vaginal infections may affect susceptibility to and clearance of human papillomavirus (HPV) infection and chronic inflammation has been linked to carcinogenesis. This study aimed to evaluate the association between bacterial vaginosis (BV) and inflammatory response (IR) with the severity of cervical neoplasia in HPV-infected women. HPV DNA was amplified using PGMY09/11 primers and genotyping was performed using a reverse line blot hybridization assay in 211 cervical samples from women submitted to excision of the transformation zone. The bacterial flora was assessed in Papanicolaou stained smears, and positivity for BV was defined as ≥ 20% of clue cells. Present inflammatory response was defined as ≥ 30 neutrophils per field at 1000× magnification. Age higher than 29 years (OR:1.91 95% CI 1.06-3.45), infections by the types 16 and/or 18 (OR:1.92 95% CI 1.06-3.47), single or multiple infections associated with types 16 and/or 18 (OR: 1.92 CI 95% 1.06-3.47), BV (OR: 3.54 95% CI 1.62-7.73) and IR (OR: 6.33 95% CI 3.06-13.07) were associated with severity of cervical neoplasia (CIN 2 or worse diagnoses), while not smoking showed a protective effect (OR: 0.51 95% CI 0.26-0.98). After controlling for confounding factors, BV(OR: 3.90 95% CI 1.64-9.29) and IR (OR: 6.43 95% CI 2.92-14.15) maintained their association with the severity of cervical neoplasia. Bacterial vaginosis and inflammatory response were independently associated with severity of cervical neoplasia in HPV-positive women, which seems to suggest that the microenvironment would relate to the natural history of cervical neoplasia.

Correlation of plasma nitrite/nitrate levels and inducible nitric oxide gene expression among women with cervical abnormalities and cancer

Cervical cancer is caused by infection with high risk human papillomavirus (HR-HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in chronic inflammation, may modulate cervical cancer risk among HPV infected women. The aim of the study was to measure and correlate plasma nitrite/nitrate levels with tissue specific expression of iNOS mRNA among women with different grades of cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and invasive cancer) and 35 women without cervical abnormalities. Inducible nitric oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the same study subjects were measured. Single nucleotide polymorphism (SNP) analysis was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels were compared across disease stage using linear and logistic regression analysis. Compared to normal controls, women diagnosed with HSIL or invasive cancer had a significantly higher concentration of plasma nitrite/nitrate and a higher median fold-change in iNOS mRNA gene expression. Genotyping of the promoter region showed three different variations: A pentanucleotide repeat (CCTTT) n, −1026T > G (rs2779249) and a novel variant −1153T > A. These variants were associated with increased levels of plasma nitrite/nitrate across all disease stages. The higher expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous lesions suggests a role for nitric oxide in the natural history of cervical cancer.

Abstract IA09: IL-17 and GMCSF may be novel markers for detection of ICC

Abstract IA09: IL-17 and GMCSF may be novel markers for detection of ICC