Are associations between HIV and human papillomavirus transmission due to behavioural confounding or biological effects?

ObjectivesCohort studies have shown significant increased risk of HIV acquisition following human papillomavirus (HPV) detection and increased risk of new HPV detection in individuals with HIV infection, after adjusting for behavioural risk factors. This study uses an individual-based model to assess whether confounding sexual behaviour factors and network level effects can explain these associations between HIV and HPV infection status, without biological interactions.MethodsThe model simulates infection with 13 oncogenic HPV types and HIV. It allows for different relationship types, with heterogeneity in probabilities of concurrency and rates of partner change. No effect of prevalent HPV infection on HIV acquisition is assumed and vice versa. The model is calibrated to South African HIV and type-specific HPV prevalence data using a Bayesian approach. The model is used to simulate cohorts with quarterly HIV and HPV testing from 2000 to 2002. These simulated data are analysed using proportional hazard models.ResultsThe mean of the unadjusted HRs of HIV acquisition following detection of an oncogenic HPV type calculated for each simulated cohort is 2.6 (95% CI 2.2 to 3.1). The mean of the unadjusted HRs for the effect of HIV on newly detected HPV is 2.5 (95% CI 2.2 to 2.8). Simulated associations between HIV and HPV infection status are similar to corresponding empirical estimates. In sensitivity analyses in which HIV and HPV were assumed to increase each other’s transmission risk, simulated associations were stronger but not inconsistent with empirical estimates.ConclusionsAlthough we cannot rule out the possibility that associations between HIV and HPV transmission may be due in part to biological interactions, these results suggest that observed associations could be explained entirely by residual confounding by behavioural factors and network-level effects that observational studies cannot account for.

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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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The Potential Role of Human Papillomavirus Infection in Bell's Palsy: A Hypothesis-Generating Study Based on a Nationwide Cohort

Frontiers in Medicine ◽

10.3389/fmed.2021.616873 ◽

2021 ◽

Vol 8 ◽

Author(s):

Kuan-Ying Li ◽

Mei-Chia Chou ◽

Renin Chang ◽

Hei-Tung Yip ◽

Yao-Min Hung ◽

...

Keyword(s):

Human Papillomavirus ◽

Index Date ◽

Hpv Infection ◽

Bell’S Palsy ◽

Sensitivity Analyses ◽

Chronic Obstructive ◽

Bell's Palsy ◽

Increased Risk ◽

The Impact

Objective: Our purpose was to investigate whether people with a previous human papillomavirus (HPV) infection were associated with an increased risk of Bell's palsy (BP).Methods: By using Taiwan population-based data, patients aged > 18 years with HPV infection (n = 22,260) from 2000 to 2012 were enrolled and compared with control subjects who had never been diagnosed with an HPV infection at a 1:4 ratio matched by sex, age, index date, and co-morbidities (n = 89,040). The index date was the first date of HPV diagnosis. All the patients were tracked until the occurrence of BP. Cox proportional hazards regression was applied to estimate the hazard ratios (HRs) for the development of BP in both groups.Results: The HPV group had 1.25 [95% confidence interval (CI) = 1.03–1.51] times higher risk of BP compared with the non-HPV group after adjusting for sex, age, and co-morbidities. The association of HPV and BP was significant in the sensitivity analyses. In the subgroup analysis, the impact of HPV infection on the risk of BP was more pronounced in the elderly > 50 years [adjusted hazard ratio (aHR) =1.86; 95% CI = 1.37–2.52], hypertension (aHR = 1.65; 95% CI = 1.17–2.31), and chronic obstructive pulmonary disease (aHR = 2.14, 95% CI 1.333.43) subgroups.Conclusions: Patients with HPV infection have a higher risk of subsequent BP compared with non-HPV patients. More rigorous studies are needed to confirm if and how specific HPV genotypes are associated with BP and the possible role of vaccines in disease prevention.

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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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Detection of aflatoxin B1 adducts in Mexican women with cervical lesions

World Mycotoxin Journal ◽

10.3920/wmj2020.2602 ◽

2021 ◽

pp. 1-12

Author(s):

L. Díaz de León-Martínez ◽

C.M. López-Mendoza ◽

Y. Terán-Figueroa ◽

R. Flores-Ramírez ◽

F. Díaz-Barriga ◽

...

Keyword(s):

Human Papillomavirus ◽

Dna Adducts ◽

Hpv Infection ◽

Mexican Women ◽

Cervical Lesions ◽

Increased Risk ◽

Secondary Objective ◽

E6 And E7 ◽

Aflatoxin B ◽

Potent Carcinogen

Cervical cancer (CC) is one of the most serious threats to the lives of women; co-factors in addition to oncogenic human papillomavirus (HPV) infection may be important in causing CC. Women in Mexico are exposed to dietary aflatoxin B1, a potent carcinogen, which may act as a co-factor, in inducing progression to CC. Scarce studies are addressing environmental risks associated with the development of CC, thus the study aimed to establish a relationship between the presence of AFB1 and the detection of human papillomavirus in the genome of Mexican women. Forty samples from cervical tissue of women infected with HPV were obtained; positive results regarding the HPV type (16 and/or 18) were found in 92.5% women and the presence of AFB1-DNA adducts were detected in 77.5% of the same positive HPV samples. Detection of AFB1-DNA adducts and genomic concentrations were correlated with the detection of two oncogenic types of HPV 16 and 18. AFB1-DNA positivity and higher genomic concentrations of AFB1-DNA adducts were correlated with an increased risk of oncogenic detection of HPV in cervical samples from women in Mexico. As a secondary objective, a hypothetical interaction of the adducts with the NRF2 pathway has been proposed, therefore activation of p62 and in turn E6 and E7 (HPV proteins) would inhibit the formation of autophagosomes, which would result in a presence or recurrence of CC.

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Prevalence and Genotype distribution of Human Papillomavirus Infection in Different Anatomical Sites among Men Who Have Sex with Men (MSM): A Systematic Review and Meta-Analysis

10.21203/rs.3.rs-17873/v1 ◽

2020 ◽

Author(s):

Mohammad Farahmand ◽

Seyed Hamidreza Monavari ◽

Ahmad Tavakoli

Keyword(s):

Systematic Review ◽

Human Papillomavirus ◽

High Risk ◽

Sexual Behaviors ◽

Meta Analysis ◽

Hpv Infection ◽

Genotype Distribution ◽

Increased Risk ◽

Pertinent Data ◽

Sex With Men

Abstract Background: Homosexual men or men who have sex with men (MSM) are at increased risk of human papillomavirus (HPV) infection because of their high-risk sexual behaviors. In this large study, a meta-analytic approach was used to systematically analyze the literature to elucidate the prevalence and genotype distribution of anal, penile, oral, and urethral HPV infection among MSM in the world.Methods: To carry out this systematic review, five electronic databases were searched for relevant studies published from January 2012 through to November 2019, and pertinent data were collected from the eligible articles. The pooled HPV prevalences were calculated for each anatomical region using random-effect model weighted by the inverse variance method. Subgroup analyses were performed to identify the probable sources of heterogeneity. The meta-analysis was performed using the “Metaprop” function in the R package Meta.Results: The overall pooled prevalence of anal, penile, oral, and urethral HPV infection among MSM were 78.11 % (95% CI: 75.50%-80.52%), 36.26% (95% CI: 29.13%–44.05%), 17.33% (95% CI: 13.65%–21.75%), and 15.40% (95% CI: 7.86%–27.97%), respectively. Stratified analyses showed that the prevalences of HPV were significantly higher in HIV-positive than HIV-negative MSM. The most frequent HPV high-risk type detected in the anus, penis, and oral cavity was HPV-16 (20.32%, 4.96%, and 3.16%, respectively). Conclusion: HPV infection is on the dramatic rise in MSM because of high-risk sexual behaviors, strongly suggesting the increased risk of developing HPV-related diseases and malignancies in this population. Among different sexual orientations, male homosexuality is associated with the highest risk of acquiring sexually transmitted infections.

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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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Knowledge of human papillomavirus and Pap test among Brazilian university students

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.65.5.625 ◽

2019 ◽

Vol 65 (5) ◽

pp. 625-632 ◽

Cited By ~ 1

Author(s):

Aimée Denzeler Baptista ◽

Carolina Xavier Simão ◽

Vitoria Carvalho Guimarães dos Santos ◽

Juliana Gil Melgaço ◽

Silvia Maria Baeta Cavalcanti ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

University Students ◽

Pap Test ◽

Hpv Infection ◽

Health Science ◽

Cancer Information ◽

Papanicolaou Test ◽

Factors Associated ◽

Increased Risk

SUMMARY OBJECTIVE: Human papillomavirus (HPV) is the most prevalent sexually transmitted virus in the world and is associated with an increased risk of cervical cancer. The most effective approach to cervical cancer control continues to be screening through the preventive Papanicolaou test (Pap test). This study analyzes the knowledge of university students of health science programs as well as undergraduate courses in other areas of knowledge on important questions regarding HPV. METHOD: Four hundred and seventy-three university students completed a questionnaire assessing their overall knowledge regarding HPV infection, cervical cancer, and the Pap test. A descriptive analysis is presented, and multivariate analysis using logistic regression identified factors associated with HPV/cervical cancer information. RESULTS: Knowledge was higher for simple HPV-related and Pap test questions but was lower for HPV interrelations with genital warts and cervical cancer. Being from the health science fields and having high income were factors associated with greater knowledge. Only the minority of the participants recognized all the situations that increased the risk of virus infection presented in the questionnaire. CONCLUSIONS: These findings highlight the need for educational campaigns regarding HPV infection, its potential as a cervical cancer agent and the forms of prevention available.

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Associations of treated and untreated human papillomavirus infection with preterm delivery and neonatal mortality: A Swedish population-based study

PLoS Medicine ◽

10.1371/journal.pmed.1003641 ◽

2021 ◽

Vol 18 (5) ◽

pp. e1003641

Author(s):

Johanna Wiik ◽

Staffan Nilsson ◽

Cecilia Kärrberg ◽

Björn Strander ◽

Bo Jacobsson ◽

...

Keyword(s):

Human Papillomavirus ◽

Neonatal Mortality ◽

Preterm Delivery ◽

Previous Treatment ◽

Study Groups ◽

Hpv Infection ◽

Population Based ◽

Abnormal Cytology ◽

Increased Risk ◽

Prelabor Rupture Of Membranes

Background Treatment of cervical intraepithelial neoplasia (CIN) is associated with an increased risk of preterm delivery (PTD) although the exact pathomechanism is not yet understood. Women with untreated CIN also seem to have an increased risk of PTD. It is unclear whether this is attributable to human papillomavirus (HPV) infection or other factors. We aimed to investigate whether HPV infection shortly before or during pregnancy, as well as previous treatment for CIN, is associated with an increased risk of PTD and other adverse obstetric and neonatal outcomes. Methods and findings This was a retrospective population-based register study of women with singleton deliveries registered in the Swedish Medical Birth Register 1999–2016 (n = 1,044,023). The study population had a mean age of 30.2 years (SD 5.2) and a mean body mass index of 25.4 kg/m2 (SD 3.0), and 44% of the women were nulliparous before delivery. Study groups were defined based on cervical HPV tests, cytology, and histology, as registered in the Swedish National Cervical Screening Registry. Women with a history of exclusively normal cytology (n = 338,109) were compared to women with positive HPV tests (n = 2,550) or abnormal cytology (n = 11,727) within 6 months prior to conception or during the pregnancy, women treated for CIN3 before delivery (n = 23,185), and women with CIN2+ diagnosed after delivery (n = 33,760). Study groups were compared concerning obstetric and neonatal outcomes by logistic regression, and comparisons were adjusted for socioeconomic and health-related confounders. HPV infection was associated with PTD (adjusted odds ratio [aOR] 1.19, 95% CI 1.01–1.42, p = 0.042), preterm prelabor rupture of membranes (pPROM) (aOR 1.52, 95% CI 1.18–1.96, p < 0.001), prelabor rupture of membranes (PROM) (aOR 1.24, 95% CI 1.08–1.42, p = 0.002), and neonatal mortality (aOR 2.69, 95% CI 1.25–5.78, p = 0.011). Treatment for CIN was associated with PTD (aOR 1.85, 95% CI 1.76–1.95, p < 0.001), spontaneous PTD (aOR 2.06, 95% CI 1.95–2.17, p < 0.001), pPROM (aOR 2.36, 95% CI 2.19–2.54, p < 0.001), PROM (aOR 1.11, 95% CI 1.05–1.17, p < 0.001), intrauterine fetal death (aOR 1.35, 95% CI 1.05–1.72, p = 0.019), chorioamnionitis (aOR 2.75, 95% CI 2.33–3.23, p < 0.001), intrapartum fever (aOR 1.24, 95% CI 1.07–1.44, p = 0.003), neonatal sepsis (aOR 1.55, 95% CI 1.37–1.75, p < 0.001), and neonatal mortality (aOR 1.79, 95% CI 1.30–2.45, p < 0.001). Women with CIN2+ diagnosed within 3 years after delivery had increased PTD risk (aOR 1.18, 95% CI 1.10–1.27, p < 0.001). Limitations of the study include the retrospective design and the fact that because HPV test results only became available in 2007, abnormal cytology was used as a proxy for HPV infection. Conclusions In this study, we found that HPV infection shortly before or during pregnancy was associated with PTD, pPROM, PROM, and neonatal mortality. Previous treatment for CIN was associated with even greater risks for PTD and pPROM and was also associated with PROM, neonatal mortality, and maternal and neonatal infectious complications.

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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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Vaginal microbiota and human papillomavirus infection among young Swedish women

npj Biofilms and Microbiomes ◽

10.1038/s41522-020-00146-8 ◽

2020 ◽

Vol 6 (1) ◽

Cited By ~ 1

Author(s):

Liqin Cheng ◽

Johanna Norenhag ◽

Yue O. O. Hu ◽

Nele Brusselaers ◽

Emma Fransson ◽

...

Keyword(s):

Human Papillomavirus ◽

Alpha Diversity ◽

Hpv Infection ◽

Cross Sectional Study ◽

Vaginal Microbiota ◽

Microbial Composition ◽

Cross Sectional ◽

Sexually Transmitted ◽

Hpv Types ◽

Oncogenic Hpv

Abstract Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. To define the HPV-associated microbial community among a high vaccination coverage population, we carried out a cross-sectional study with 345 young Swedish women. The microbial composition and its association with HPV infection, including 27 HPV types, were analyzed. Microbial alpha-diversity was found significantly higher in the HPV-infected group (especially with oncogenic HPV types and multiple HPV types), compared with the HPV negative group. The vaginal microbiota among HPV-infected women was characterized by a larger number of bacterial vaginosis-associated bacteria (BVAB), Sneathia, Prevotella, and Megasphaera. In addition, the correlation analysis demonstrated that twice as many women with non-Lactobacillus-dominant vaginal microbiota were infected with oncogenic HPV types, compared with L. crispatus-dominated vaginal microbiota. The data suggest that HPV infection, especially oncogenic HPV types, is strongly associated with a non-Lactobacillus-dominant vaginal microbiota, regardless of age and vaccination status.

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