Association Between Common Vaginal Infections and Cervical Non–Human Papillomavirus (HPV) 16/18 Infection in HPV-Vaccinated Women

Abstract Background How vaginal infections such as bacterial vaginosis, Candida spp, and Trichomonas vaginalis affect persistence of human papillomavirus (HPV) infection is not well established. Our study aimed to evaluate the association between common vaginal infections and cervical non-HPV16/18 infection, as risk factors associated with persistence of nonvaccine HPV types will become increasingly relevant in the setting of HPV vaccination. Methods We performed an analysis in 2039 AS04-HPV16/18–vaccinated women enrolled in a phase II/III trial in China, who were HPV DNA negative at month 0 and 6 and had at least 1 subsequent follow-up visit. Vaginal infections were detected in liquid-based cytology according to the diagnostic criteria of the Bethesda System. Associations between vaginal infections and incident and 6-month persistent non-HPV16/18 infections in the cervix were evaluated using generalized estimating equations, adjusting for the age at initial vaccination, as well as HPV types in the persistence analysis. Results Study visits with any vaginal infection had a statistically significant increased risk of incident non-HPV16/18 infection compared to those without vaginal infections (odds ratio [OR], 1.44 [95% confidence interval {CI}, 1.09–1.92]). However, vaginal infections were not associated with 6-month persistent non-HPV16/18 infection (OR, 1.02 [95% CI, .62–1.69]). Conclusions Our study suggests that common vaginal infections are not associated with persistence of non-HPV16/18 infection among HPV16/18-vaccinated women.

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Human papillomavirus-driven immune deviation: challenge and novel opportunity for immunotherapy

Therapeutic Advances in Vaccines ◽

10.1177/2051013617717914 ◽

2017 ◽

Vol 5 (3) ◽

pp. 69-82 ◽

Cited By ~ 25

Author(s):

Sigrun Smola ◽

Connie Trimble ◽

Peter L. Stern

Keyword(s):

Human Papillomavirus ◽

Immune System ◽

Immune Escape ◽

Hpv Vaccination ◽

Suppressor Cells ◽

Clinical Problem ◽

Hpv Infection ◽

Treatment Protocols ◽

Increased Risk ◽

Risk Of Cancer

It is now recognized that the immune system can be a key component of restraint and control during the neoplastic process. Human papillomavirus (HPV)-associated cancers of the anogenital tract and oropharynx represent a significant clinical problem but there is a clear opportunity for immune targeting of the viral oncogene expression that drives cancer development. However, high-risk HPV infection of the target epithelium and the expression of the E6/E7 oncogenes can lead to early compromise of the innate immune system (loss of antigen-presenting cells) facilitating viral persistence and increased risk of cancer. In these circumstances, a succession of interacting and self-reinforcing events mediated through modulation of different immune receptors, chemokine and cytokine responses (CCL20; CCL2; CCR2; IL-6; CCR7; IL-12) further promote the generation of an immune suppressive microenvironment [increased levels of Tregs, Th17, myeloid-derived suppressor cells (MDSCs) and PD-L1]. The overexpression of E6/E7 expression also compromises the ability to repair cellular DNA, leading to genomic instability, with the acquisition of genetic changes providing for the selection of advantaged cancer cells including additional strategies for immune escape. Therapeutic vaccines targeting the HPV oncogenes have shown some encouraging success in some recent early-phase clinical trials tested in patients with HPV-associated high-grade anogenital lesions. A significant hurdle to success in more advanced disease will be the local and systemic immune suppressive factors. Interventions targeting the different immunosuppressive components can provide opportunity to release existing or generate new and effective antitumour immunity. Treatments that alter the protumour inflammatory environment including toll-like receptor stimulation, inhibition of IL-6-related pathways, immune-checkpoint inhibition, direct modulation of MDSCs, Tregs and macrophages could all be useful in combination with therapeutic HPV vaccination. Future progress in delivering successful immunotherapy will depend on the configuration of treatment protocols in an insightful and timely combination.

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Distribution and Prevalence of High-Risk Human Papillomavirus Genotypes in Cervical Specimens

Flora the Journal of Infectious Diseases and Clinical Microbiology ◽

10.5578/flora.68958 ◽

2020 ◽

Vol 25 (3) ◽

pp. 325-331

Author(s):

Erkan Özmen ◽

Ülkü Altoparlak ◽

Muhammet Hamidullah Uyanık ◽

Abdulkadir Gülen

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Age Groups ◽

Hpv Infection ◽

High Rate ◽

Genotype Distribution ◽

Hpv Dna ◽

Hpv Test ◽

Significant Difference ◽

Hpv Types

Introduction: Human papillomavirus (HPV) is frequently a sexually transmitted virus and can cause cervical cancer in women. Cervical cancer is the second most common type of cancer among the developing countries. In this study, cervical HPV DNA positivity and genotype distributions were investigated in female patients living in our region and the results were compared with different studies. Materials and Methods: Between 1 July, 2017 and 1 March, 2019, 433 cervical swabs were sent to Ataturk University, Medical Faculty Hospital, Medical Microbiology Laboratory due to suspicion of HPV. Swab samples were evaluated for HPV virus using molecular (Polymerase Chain Reaction-PCR) methods. For this purpose, Xpert HPV Test (Cepheid, Inc, Sunnyvale, CA) was used to identify HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 t in a single sample. Results: Mean age of the patients ranged from 20 to 69 years, with a mean of 39.8 years (± 10.0). Positivity was detected in 62 of the 433 patients. Mean age of the positive patients was 40.2 years (± 11.3). When the positive patients were examined in terms of HPV types, the presence of HPV 16 was observed with a rate of 25.6%, while the HPV 18/45 types were found to be 9.0% in total. When patients were evaluated according to age groups, HPV DNA positivity was highest in the 25-34 age group with 38.7%. In our statistical study, there was no significant difference in HPV DNA positivity rate between the ages of 35 and under 35 years. Conclusion: This study demonstrates the prevalence and viral genotype distribution of HPV infection in women in Erzurum region. HPV type 16 is seen with a high rate in our region.

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Human papillomavirus vaccination: evidence base for efficacy and safety

GYNECOLOGY ◽

10.26442/20795696.2021.2.200742 ◽

2021 ◽

Vol 23 (2) ◽

pp. 125-130

Author(s):

Yuliya E. Dobrokhotova ◽

Ekaterina I. Borovkova

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Hpv Vaccination ◽

Intraepithelial Neoplasia ◽

Evidence Base ◽

Hpv Infection ◽

Efficacy And Safety ◽

Human Papillomavirus Vaccination ◽

Hpv Types ◽

Further Development

The article provides a literature review on the prevention of cervical cancer by human papillomavirus (HPV) vaccination. Currently, 3 vaccines are available: the 4-valent vaccine against HPV types 6, 11, 16 and 18, the 9-valent vaccine against HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58 and the bivalent vaccine against HPV types 16 and 18. Vaccination provides protection for women and men against infection with HPV and further development of HPV-associated diseases. Following immunization, seroconversion develops in 93-100% of women and in 99-100% of men and is effective in preventing incident and persistent HPV infection as well as cervical intraepithelial neoplasia. HPV immunization is ineffective in treating an existing HPV infection, genital warts, or anogenital intraepithelial neoplasia. HPV vaccination status does not affect recommendations for cervical cancer screening.

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Human papillomavirus, coinfection with Schistosoma hematobium, and cervical neoplasia in rural Tanzania

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200307000-00015 ◽

2003 ◽

Vol 13 (4) ◽

pp. 505-509 ◽

Cited By ~ 4

Author(s):

K. U. Petry ◽

U. Scholz ◽

B. Hollwitz ◽

R. Von Wasielewski ◽

C. J.L.M. Meijer

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Invasive Cervical Cancer ◽

Clinical History ◽

Hpv Infection ◽

Separate Analysis ◽

Hpv Dna ◽

Rural Tanzania ◽

Increased Risk ◽

Local Immunosuppression

Cervical cancer is the most common malignant tumor among women in Tanzania and other countries in tropical Africa. Genital schistosomiasis has been proposed as a possible cofactor in the genesis of this malignant disease that might contribute to its high incidence in regions where bilharzias is endemic. One hundred nine Tanzanian patients from an area with endemic bilharzias who were transferred to a gynecologic out-patient clinic were age-matched with 109 German controls. In patients and controls, separate samples were taken for cytologic assessment and human papillomavirus (HPV) DNA detection using the Hybrid Capture 2 assay (HC2) and PCR (GP5+/6 +). Samples that tested positive for HPV DNA with general primers were re-tested with HPV type-specific primers. After application of 3% acetic acid, punch biopsies were taken from any cervical lesion. Patients were interviewed for recent symptoms or clinical history suggestive of bilharzias. Urine samples from all patients were examined for the presence of schistosoma hematobium ova. Additionally six Tanzanian patients with invasive cervical cancer were included for separate analysis. Patients and controls had an identical prevalence of HPV-DNA (21.5%) using HC2. Based on PCR results with general primers, the corresponding prevalence was 34.5% for Tanzanian cases and 26.9% for German controls. A history suggestive of bilharzias and/or active schistosomiasis were associated with a significantly increased risk for infection with high-risk HPV types. We conclude that infection with Schistosoma hematobium seems to favor persistent genital HPV infection either by traumatizing the genital epithelium and/or by local immunosuppression.

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Human Papillomavirus and Coronary Artery Disease in Climacteric Women: Is There an Association?

The Scientific World JOURNAL ◽

10.1155/2019/1872536 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Luciane Maria Oliveira Brito ◽

Haissa Oliveira Brito ◽

Rita da Graça Carvalhal Frazão Corrêa ◽

Clariano Pires de Oliveira Neto ◽

Joyce Pinheiro Leal Costa ◽

...

Keyword(s):

Coronary Artery Disease ◽

Human Papillomavirus ◽

Coronary Artery ◽

Sexual Behaviors ◽

Hpv Infection ◽

Demographic Variables ◽

Hpv Dna ◽

Hpv Types ◽

Artery Disease ◽

High Risk Hpv

Background. Cardiovascular diseases are leading causes of death worldwide. Recent studies suggest that infection by some viruses, including the human papillomavirus (HPV), may increase the risk of developing atheromatous lesions on coronary arteries. However, there is a lack of data regarding the possible association between HPV infection and coronary artery disease (CAD) in women. Objective. To investigate whether HPV infection is associated with the occurrence of CAD among climacteric women. Methods. The presence of CAD and cervical HPV DNA was investigated in 52 climacteric women. Social and demographic variables and metabolic profiles were also investigated. Results. Among 27 women with CAD, 16 were positive for HPV, whereas 11 were negative. The presence of cervical HPV was strongly associated with CAD, after adjusting for demographic variables, health and sexual behaviors, comorbidities, and known cardiovascular risk factors. HPV-positive women showed a greater likelihood of having CAD (odds ratio [OR] = 3.74; 95% confidence interval [CI]: 1.16 to 11.96) as compared with HPV-negative women, particularly those infected with high-risk HPV types (OR = 4.90; 95% CI: 1.26 to 19.08). Conclusion. These results support the hypothesis that HPV infection might be associated with CAD among climacteric women, though further studies are needed to investigate the mechanisms involved.

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

Infectious Diseases in Obstetrics and Gynecology ◽

10.1155/2008/587082 ◽

2008 ◽

Vol 2008 ◽

pp. 1-7 ◽

Cited By ~ 11

Author(s):

Howard Minkoff ◽

Ye Zhong ◽

Howard D. Strickler ◽

D. Heather Watts ◽

Joel M. Palefsky ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Pap Smear ◽

Crack Cocaine ◽

Hpv Infection ◽

Cocaine Use ◽

Hpv Dna ◽

Increased Risk ◽

Hiv Seropositive ◽

Oncogenic Hpv

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

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Type-Specific Identification of Genital Human Papillomavirus Infection in Women with Cytological Abnormality

Acta Cytologica ◽

10.1159/000446389 ◽

2016 ◽

Vol 60 (3) ◽

pp. 211-216

Author(s):

Hernán Vargas ◽

Jenny P. Sánchez ◽

Mónica L. Guerrero ◽

Leider T. Ortiz ◽

Dayanne M. Rodríguez ◽

...

Keyword(s):

Human Papillomavirus ◽

Pap Smear ◽

Hpv Vaccination ◽

Hpv Infection ◽

Epidemiological Surveillance ◽

Molecular Technique ◽

Genotype Distribution ◽

Vaccination Programs ◽

Hpv Dna ◽

Cytological Abnormality

Objectives: To estimate the frequency of human papillomavirus (HPV) infection and the genotype distribution of HPV among women with a Pap smear showing atypical squamous cells of undetermined significance (ASC-US) attending the Program for the Detection and Control of Cervical Cancer in Bogotá, Colombia. Study Design: Cervical samples from 200 women with an ASC-US Pap smear were analyzed for the presence of HPV DNA and genotype distribution using a commercial molecular technique (Linear Array®; Roche Molecular Systems, USA). Results: HPV infection was found in 140 women (70%). High-risk HPV types were present in 46.4% of the samples; 16.4% showed a low-risk HPV type, and 37.1% showed both. Of the positive samples, 42.9% were infected with a single viral genotype, whereas 57.1% exhibited multiple HPV infections. The most common HPV genotypes were HPV 16, 53, and 52 with a prevalence of 26.4, 16.4, and 13.6%, respectively. Conclusion: The epidemiological characterization of HPV infections described in this study might guide actions for epidemiological surveillance to strengthen the program in Bogotá and to develop appropriate HPV vaccination programs.

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Prevalence of Oral Human Papillomavirus Infection among Indian HIV-Positive Men Who Have Sex With Men: A Cross-Sectional Study

10.21203/rs.3.rs-60960/v1 ◽

2020 ◽

Author(s):

Alexandra Lydia Hernandez ◽

Rajiv Karthik ◽

Murugesan Sivasubramanian ◽

Anantharam Raghavendran ◽

Shelly Lensing ◽

...

Keyword(s):

Human Papillomavirus ◽

Hpv Infection ◽

Sexual History ◽

Hiv Positive ◽

Increased Risk ◽

Oral Hpv ◽

Hpv Types ◽

Sex With Men ◽

The Impact ◽

Hiv Positive Men

Abstract Background: Oral human papillomavirus (HPV) infection has been causally linked to a subset of oropharyngeal cancers in Western populations15-20, and both oropharyngeal cancer and oral HPV infection are increased among HIV-positive individuals24,41. India has high incidences of oral and oropharyngeal cancers, and Indian HIV-positive men who have sex with men (MSM) may be at increased risk of developing oropharyngeal cancers. However, there is little information available on the prevalence of oral HPV in this population.Methods: We tested 302 HIV-positive Indian MSM for oral HPV infection using L1 HPV DNA PCR with probes specific for 29 types and a mixture of 10 additional types. CD4+ level and plasma HIV viral load (VL) were measured. Participants completed an interviewer-administered questionnaire including a sexual history.Results: The prevalence of oral HPV was 23.7% (95% CI: 19-29%) and 2.4% of participants had oncogenic HPV types. No participants had oral HPV type 16 (HPV-16) and the prevalence of other anogenital HPV types was low. Participants with higher CD4+ levels had reduced odds of having any oral HPV infection (OR: 3.1 [1.4-6.9]) in multivariable analyses.Conclusions: This is the first report of oral HPV among Indian HIV-positive MSM. Our results show a high prevalence of oral HPV infection consistent with studies from Western populations. However, oncogenic anogenital HPV types were relatively uncommon in our study population. It is unknown what the impact of this distribution of oral HPV will be on oropharyngeal cancers. HIV-positive MSM in India should be monitored closely for oral and oropharyngeal pre-cancer and cancer.

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Concurrent Infection With Multiple Human Papillomavirus Types Among Unvaccinated and Vaccinated 17-Year-Old Norwegian Girls

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa709 ◽

2020 ◽

Author(s):

Ida Laake ◽

Berit Feiring ◽

Christine Monceyron Jonassen ◽

John H-O Pettersson ◽

Torstein Gjølgali Frengen ◽

...

Keyword(s):

Logistic Regression ◽

Human Papillomavirus ◽

High Risk ◽

Hpv Vaccination ◽

Hpv Infection ◽

Concurrent Infection ◽

Birth Cohorts ◽

Mixed Effect ◽

Hpv Genotypes ◽

Hpv Types

Abstract Background Whether type-specific human papillomavirus (HPV) infection influences the risk of acquiring infections with other HPV types is unclear. We studied concurrent HPV infections in 17-year-old girls from 2 birth cohorts; the first vaccine-eligible cohort in Norway and a prevaccination cohort. Methods Urine samples were collected and tested for 37 HPV genotypes. This study was restricted to unvaccinated girls from the prevaccination cohort (n = 5245) and vaccinated girls from the vaccine-eligible cohort (n = 4904). Risk of HPV infection was modelled using mixed-effect logistic regression. Expected frequencies of concurrent infection with each pairwise combination of the vaccine types and high-risk types (6/11/16/18/31/33/35/39/45/51/52/56/58/59) were compared to observed frequencies. Results Infection with multiple HPV types was more common among unvaccinated girls than vaccinated girls (9.2% vs 3.7%). HPV33 and HPV51 was the only HPV pair that was detected together more often than expected among both unvaccinated (P = .002) and vaccinated girls (P < .001). No HPV pairs were observed significantly less often than expected. Conclusions HPV33 and HPV51 tended to be involved in coinfection among both unvaccinated and vaccinated girls. The introduction of HPV vaccination does not seem to have had an effect on the tendency of specific HPV types to cluster together.

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Association between Vaginal Infections and the Types and Viral Loads of Human Papillomavirus: A Clinical Study Based on 4,449 Cases of Gynecologic Outpatients

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2020/9172908 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Wei Wang ◽

Xian-hui Zhang ◽

Mei Li ◽

Chong-hua Hao ◽

Hong-ping Liang

Keyword(s):

Human Papillomavirus ◽

Trichomonas Vaginalis ◽

Hpv Infection ◽

Vaginal Infection ◽

Vaginal Infections ◽

Viral Loads ◽

Vaginal Secretions ◽

Positive Rate ◽

High Risk Hpv ◽

Viral Load Determination

Objective. We here evaluated the association between human papillomavirus (HPV) infection and vaginal infections, including bacterial vaginosis (BV), trichomonas vaginalis (TV), and vulvovaginal candidiasis (VVC). Methods. A total of 4,449 women were enrolled in this study and given gynecological examinations. HPV genotyping and viral load determination were performed using a real-time PCR. Vaginal infections were diagnosed using wet mounts of vaginal secretions, gram-stained vaginal secretion smears, and chemical enzyme kits. Results. In this study, the overall HPV-positive rate was 25.06%, and vaginal infection tended to occur in women with HPV infection (P<0.05). HPV infection tended to occur in BV- and TV-positive women (P<0.05) and not in women with microecological disorders, intermediate type BV, VVC, or coinfection (P>0.05). The most common genotypes were HPV58 and HPV53 in women with normal vaginal microecology and HPV16 and HPV52 in the women suffering from vaginal infection. The viral loads among groups for HPV16 and HPV52 showed no statistically significant differences (P=0.940; P=0.167). Conclusions. Our study revealed that BV and TV are associated with HPV infection, especially high-risk HPV infection, while VVC has no association with HPV infection. Further studies are needed to explore the detailed mechanism.

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