Human Papillomavirus Clearance Research Articles

Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection.

We sought to describe the temporal relationship between vaginal microbiota and human papillomavirus (HPV) detection. Thirty-two reproductive-age women self-collected midvaginal swabs twice weekly for 16 weeks (937 samples). Vaginal bacterial communities were characterized by pyrosequencing of barcoded 16S rRNA genes and clustered into 6 community state types (CSTs). Each swab was tested for 37 HPV types. The effects of CSTs on the rate of transition between HPV-negative and HPV-positive states were assessed using continuous-time Markov models. Participants had an average of 29 samples, with HPV point prevalence between 58%-77%. CST was associated with changes in HPV status (P<.001). Lactobacillus gasseri-dominated CSTs had the fastest HPV remission rate, and a low Lactobacillus community with high proportions of the genera Atopobium (CST IV-B) had the slowest rate compared to L. crispatus-dominated CSTs (adjusted transition rate ratio [aTRR], 4.43, 95% confidence interval [CI], 1.11-17.7; aTRR, 0.33, 95% CI, .12-1.19, respectively). The rate ratio of incident HPV for low Lactobacillus CST IV-A was 1.86 (95% CI, .52-6.74). Vaginal microbiota dominated by L. gasseri was associated with increased clearance of detectable HPV. Frequent longitudinal sampling is necessary for evaluation of the association between HPV detection and dynamic microbiota.

Male circumcision and the incidence and clearance of genital human papillomavirus (HPV) infection in men: the HPV Infection in men (HIM) cohort study

BackgroundReported associations of male circumcision (MC) with human papillomavirus (HPV) infection in men have been inconsistent.Methods4,033 healthy men were examined every six months for a median of 17.5 months. In each study visit, exfoliated cell specimens from the coronal sulcus/glans penis, penile shaft, and scrotum were collected and combined into one sample per person for HPV DNA detection. Samples were tested for 37 HPV types. Cox proportional hazards models were used to evaluate the association between MC and the incidence and clearance of HPV infections and specific genotypes.ResultsThe overall incidence of new HPV infections did not differ by MC status (for any HPV, adjusted hazard ratio (aHR) 1.08, 95% confidence interval (CI) 0.91-1.27). However, incidence was significantly lower among circumcised versus uncircumcised men for HPV types 58 (p = 0.01), 68 (p < 0.001), 42 (p = 0.01), 61 (p < 0.001), 71 (p < 0.001), 81 (p = 0.04), and IS39 (p = 0.01), and higher for HPV types 39 (p = 0.01) and 51 (p = 0.02). Despite the lack of an overall association in the risk of HPV clearance by MC (for any HPV, aHR 0.95, 95% CI 0.88-1.02), median times to clearance were significantly shorter among circumcised than uncircumcised men for HPV types 33 (p = 0.02) and 64 (p = 0.04), and longer for HPV types 6 (p < 0.001), 16 (p < 0.001), and 51 (p = 0.02).ConclusionsMC is not associated with the incidence and clearance of genital HPV detection, except for certain HPV types. The use of a single combined sample from the penis and scrotum for HPV DNA detection likely limited our ability to identify a true effect of MC at the distal penis.

Incidence, Clearance, and Disease Progression of Genital Human Papillomavirus Infection in Heterosexual Men

In this analysis, we examine the incidence and clearance of external genital human papillomavirus (HPV) infection among heterosexual males aged 16-24 years. A total of 1732 males aged 16-24 years old in the placebo arm of a quadrivalent HPV vaccine trial were included in this analysis. Participants were enrolled from 18 countries in Africa, the Asia-Pacific region, Europe, Latin America, and North America. Subjects underwent anogenital examinations and sampling of the penis, scrotum, and perineal/perianal regions. The incidence rate of any HPV DNA genotype 6, 11, 16, and/or 18 detection was 9.0 cases per 100 person-years. Rates of HPV DNA detection were highest in men from Africa. Median time to clearance of HPV genotypes 6, 11, 16, and 18 DNA was 6.1, 6.1, 7.7, and 6.2 months, respectively. Median time to clearance of persistently detected HPV 6, 11, 16, and 18 DNA was 6.7, 3.2, 9.2, and 4.7 months, respectively. The study results suggest that the acquisition of HPV 6, 11, 16, and/or 18 in males is common and that many of these so-called infections are subsequently cleared, similar to findings for women. Nevertheless, given the high rate of HPV detection among young men, HPV vaccination of males may reduce infection in men and reduce the overall burden of HPV-associated disease in the community.

Results of a phase II randomized, double-blind, placebo-controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia

ObjectiveIn vitro data and pilot data suggest that green tea catechins may possess chemopreventive activity for cervical cancer and precursor lesions. We conducted a randomized, double-blind, placebo-controlled trial of Polyphenon E (decaffeinated and enriched green tea catechin extract) in women with persistent human papillomavirus (HPV) infection and low-grade cervical intraepithelial neoplasia (CIN1) to evaluate the potential of Polyphenon E for cervical cancer prevention. MethodsNinety-eight eligible women were randomized to receive either Polyphenon E (containing 800mg epigallocatechin gallate) or placebo once daily for 4 months. The primary study outcome was oncogenic HPV clearance and clearance of CIN1. ResultsPolyphenon E was shown to be acceptable, safe and well tolerated. There was no difference in the response rate by treatment allocation. Complete response, defined as negative for high-risk HPV and normal histopathology, was noted in 7 (17.1%) and 6 (14.6%) women in the Polyphenon E and placebo arms, respectively. Progression, defined as persistent oncogenic HPV with histopathologic evidence of progression, was more common in the Polyphenon E group than in the placebo group [6 (14.6%) vs. 3 (7.7%)]. ConclusionBased on the largest randomized placebo-controlled trial of a green tea extract for HPV related cervical disease, we conclude that 4months of Polyphenon E intervention did not promote the clearance of persistent high-risk HPV and related CIN1. Further studies may be necessary to better delineate the risk factors for persistent HPV infection and biology of the disease to facilitate the evaluation of chemopreventive strategies.

Control of oral human papillomavirus (HPV) by medicinal mushrooms, Trametes versicolor and Ganoderma lucidum: a preliminary clinical trial.

This preliminary randomized study investigated the efficacy of medicinal mushrooms, Trametes versicolor (TV), Ganoderma lucidum (GL), and Laetiporus sulphureus (LS), on the clearance of oral human papillomavirus (HPV, serotypes 16 and 18). Among 472 patients who underwent oral swabs for gingivitis, 61 patients were positive for HPV16 or HPV18. Twenty patients were included in group 1 (LS) and 41 patients were included in group 2 (TV+GL) for 2 months. Polymerase chain reaction (PCR) for HPV was performed at inclusion and after 2 months. In group 1, the clearance was equal to 5% after 2 months of treatment. In group 2, the clearance was equal to 88% (P<0.001). The detection of HPV16 or HPV18 could become relevant in routine since positivity is frequent and because a harmless and costless treatment may exist. The use of TV+GL for the clearance of oral HPV deserves further investigation.

Abstract C50: Results of a phase II randomized, double-blind, placebo controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia

Abstract In vitro data and pilot clinical trial data suggest that green tea catechins may possess chemopreventive activity for cervical cancer and its precursor lesions. We conducted a randomized, double-blind, placebo controlled trial of Polyphenon E (decaffeinated and enriched green tea catechin extract) in women with persistent human papillomavirus (HPV) infection and low grade cervical intraepithelial neoplasia (CIN1) to evaluate the potentials of Polyphenon E for cervical cancer prevention. Ninety-eight eligible women were randomized to receive either Polyphenon E (containing 800 mg epigallocatechin gallate) or placebo once daily for 4 months. The primary study outcome was oncogenic HPV clearance and clearance of CIN1. Polyphenon E was shown to be acceptable, safe and well tolerated. There was no difference in the response rate by treatment allocation. Complete response, defined as negative for high risk HPV and normal histopathology, was noted in 7 (17.1%) and 6 (14.6%) women in the Polyphenon E and placebo arms, respectively. Partial response, defined as clearance of oncogenic HPV with evidence of CIN1, occurred more frequently in the placebo group 6 (14.6%) vs. 1 (2.4%) in the Polyphenon E arm. Progression, defined as persistent oncogenic HPV with histopathologic evidence of progression, was more common in the Polyphenon E group [3 (7.7%) vs. 6 (14.6%) in the placebo arm, although neither of these observations were statistically significant. Based on the largest randomized placebo-controlled trial of a green tea extract for HPV related cervical disease, we conclude that four months of Polyphenon E intervention did not promote the clearance of persistent high risk HPV and related CIN 1. Further studies may be necessary to better delineate the risk factors for persistent HPV infection and biology of the disease to facilitate the evaluation of chemopreventive strategies. Citation Format: Tomas Nuno, Francisco A.R. Garcia, Terri Cornelison, Amy L. Mitchell, David L. Greenspan, John W. Byron, Chiu-Hsieh Hsu, David S. Alberts, Sherry Chow. Results of a phase II randomized, double-blind, placebo controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C50.

Clearance of Cervical Human Papillomavirus Infection by Topical Application of Curcumin and Curcumin Containing Polyherbal Cream: A Phase II Randomized Controlled Study

Curcumin and curcumin containing polyherbal preparations have demonstrated anti-microbial and anti- viral properties in pre-clinical studies. Till date no therapeutic intervention has been proved to be effective and safe in clearing established cervical human papillomavirus (HPV) infection. The present study evaluated the efficacy of Basant polyherbal vaginal cream (containing extracts of curcumin, reetha, amla and aloe vera) and of curcumin vaginal capsules to eliminate HPV infection from cervix. Women were screened by Pap smear and HPV DNA test by PCR. HPV positive women without high grade cervical neoplasias (N=287) were randomized to four intervention arms to be treated with vaginal Basant cream, vaginal placebo cream, curcumin vaginal capsules and placebo vaginal capsules respectively. All subjects were instructed to use one application of the assigned formulation daily for 30 consecutive days except during menstruation and recalled within seven days of the last application for repeat HPV test, cytology and colposcopy. HPV clearance rate in Basant arm (87.7%) was significantly higher than the combined placebo arms (73.3%). Curcumin caused higher rate of clearance (81.3%) than placebo though the difference was not statistically significant. Vaginal irritation and itching, mostly mild to moderate, was significantly higher after Basant application. No serious adverse events were noted.

Racial Differences in the Incidence and Clearance of Human Papilloma Virus (HPV): The HPV in Men (HIM) Study

This analysis assessed the acquisition (incidence) and persistence (clearance) of human papilloma virus (HPV) infection by self-reported race among men in The HPV in Men (HIM) Study, a multinational prospective study of the natural history of genital HPV infections. Self-reported race was categorized as White, Black, Asian/Pacific Islander (PI), or multiple and mixed race. Genital samples were combined for HPV DNA testing and categorized by any, oncogenic, and non-oncogenic HPV infections. Asian/PI race had significantly the lowest incidence of any, oncogenic, and non-oncogenic HPV infection (P < 0.001). In multivariable analyses, Asian/PI race was associated with a lower probability of acquiring any [HR = 0.63; 95% confidence interval (CI), 0.42-0.95] and non-oncogenic HPV infection (HR = 0.61; 95% CI, 0.40-0.93) when compared to Whites. No significant associations were evident for Asian/PI race for clearance. Multiple and mixed race was significantly associated with lower probability of acquiring non-oncogenic HPV infection (HR = 0.83; 95% CI, 0.69-0.99) and borderline significant associations were observed for any HPV (HR = 0.91) and oncogenic infections (HR = 0.92). Multiple and mixed race was associated with a lower probability of clearing any (HR = 0.92; 95% CI, 0.84-1.00) and oncogenic HPV infections (HR = 0.85; 95% CI, 0.75-0.95). Asian/PI race had the lowest incidence of HPV and exhibited a lower probability of acquiring new HPV infections. Multiple and mixed race had the second lowest incidence of infection and was associated with a lower probability of acquiring and clearing an HPV infection. Race-specific differences in HPV infection could be due to behavior, innate genetic differences, or circulating intratypic HPV variants.

The role of human papillomavirus (HPV) testing in the follow-up of patients after treatment for cervical intraepithelial neoplasia (CIN)

Introduction: The aim of this study was to examine the role of human papillomavirus testing in the follow-up after treatment for CIN, as a prognostic sign for residual/recurrent cervical precancerous lesions.Methods: A hospital-based analysis was performed on 460 patients previously treated for CIN with cold knife conization, at the University Clinic for Gynecology and Obstetrics and General Hospital Remedika, in Skopje, Republic of Macedonia, in a period of 3 years. The patients were followed-up with HPV testing in addition to cytology, colposcopy and/or biopsy. The first after treatment HPV testing was performed8 months after cold knife conization, proceeded by follow-up within 24 months after treatment, at 4 months intervals.Results: Among 460 treated patients, at the fi rst HPV and cytologic testing, 8 months after treat-ment, 69 (15%) were HPV+, and 391 (85%) HPV negative. From the 69 HPV+ patients, 41 (59.4%) were withcytologic abnormalities and 28 (40.6%) without abnormalities. 12 months after treatment, the number of HPV+ patients developing cytologic abnormalities raised to 45/70 (64.29%). Within the 24 months aftertreatment, the number of patients who had recurrent/ residual CIN from the HPV+ patients reached 50/71 (70.42%); which was 10.87% from all 460 treated patients.Conclusion: Persistence or clearance of HPV especially 8 months after treatment even in patients with normal cytology, is an early valid prognostic marker of treatment failure, and is more accurate than cytologyat the same follow-up intervals.

Anal Human Papillomavirus Infection Among Thai Men Who Have Sex With Men With and Without HIV Infection

HIV-positive men who have sex with men (MSM) have a higher prevalence of anal human papillomavirus (HPV) infection and anal cancer incidence than HIV-negative MSM. High-risk HPV persistence is an important risk factor for the development of anal cancer. A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled from the Thai Red Cross AIDS Research Centre in Bangkok, Thailand, and followed for 12 months. Anal sample collection for HPV genotyping was performed at every visit. HPV prevalence, incidence, clearance, and persistence were calculated. A logistic regression model was used to study factors associated with high-risk HPV persistence. The prevalence of any anal HPV infection was 85% in HIV-positive and 58.5% in HIV-negative MSM (P < 0.0001). The prevalence of high-risk HPV infection was 57.5% in HIV-positive and 36.6% in HIV-negative MSM (P = 0.001). HPV 16 was the most common high-risk HPV type. HIV-positive MSM had a higher prevalence (22.5% vs. 9.8%, P = 0.008) and persistence (16.7% vs. 1.3%, P < 0.001) of HPV 16 than HIV-negative MSM and a trend for higher incidence (16.1 vs. 6.1 episodes/1000 person-months, incidence rate ratio 2.6, P = 0.058). HIV infection (odds ratio: 4.45, 95% confidence interval: 2.11 to 9.4, P < 0.001) and smoking in HIV-positive MSM (odds ratio: 2.3, 95% confidence interval: 1.17 to 4.5, P = 0.015) were independently associated with high-risk HPV persistence in multivariate models. In addition to targeting HIV-positive MSM who are at higher risk for anal, high-risk HPV persistence, anal cancer prevention programs should also integrate behavioral interventions such as smoking cessation to modify risk for high-risk HPV persistence.

Detection of oncogenic human papillomavirus genotypes on spermatozoa from male partners of infertile couples

To evaluate the prevalence of human papillomavirus (HPV) sperm infection and its correlation with sperm parameters in patients who attended a fertility clinic. Cross-sectional clinical study. University-affiliated reproductive medicine clinic. A total of 308 male partners of couples undergoing in vitro fertilization techniques. Specimens of semen were collected from all patients. Sperm parameters were evaluated according to the World Health Organization manual. The presence of HPV DNA was researched by the combined use of two HPV assays and a highly sensitive nested polymerase chain reaction assay followed by HPV genotyping. To examine whether HPV was associated with the sperm, in situ hybridization (ISH) analysis was performed. Results of HPV investigation were compared with sperm parameters and ISH analysis. Twenty-four out of 308 semen samples (7.8%) were HPV DNA positive, but HPV infection did not seem to affect semen quality. Moreover, ISH revealed a clear HPV localization at the equatorial region of sperm head in infected samples. Oncogenic HPV genotypes were detected on spermatozoa from asymptomatic subjects, but a role of the infection in male infertility was not demonstrated.

Association of tumor necrosis factor-alpha promoter variants with risk of HPV-associated oral squamous cell carcinoma

BackgroundTumor necrosis factor alpha (TNF-α) plays an important role in inflammation, immunity, and defense against infection and clearance of human papillomavirus (HPV). Thus, genetic variants may modulate individual susceptibility to HPV-associated oral squamous cell carcinoma (OSCC).MethodsIn this study we genotyped four common single nucleotide polymorphisms (SNPs) in the TNF-α promoter [ −308G > A(rs1800629), -857C > T (rs1799724), -863C > A (rs1800630), and -1031T > C (rs1799964)] and determined HPV16 serology in 325 OSCC cases and 335 matched controls and tumor HPV status in 176 squamous cell carcinomas of the oropharynx (SCCOP) patients. Univariate and multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsWe found that HPV16 seropositivity alone was associated with an increased risk of OSCC (OR, 3.1; 95% CI, 2.1–4.6), and such risk of HPV16-associated OSCC was modified by each SNP. Patients with both HPV16 seropositivity and variant genotypes for each SNP had the highest risk when using patients with HPV16 seronegativity and a wild-type genotype as a comparison group. Moreover, similar results were observed for the combined risk genotypes of four variants and all such significant associations were more pronounced in several subgroups, particularly in SCCOP patients and never smokers. Notably, the combined risk genotypes of four variants were also significantly associated with tumor HPV-positive SCCOP.ConclusionTaken together, these results suggest that TNF-α SNPs may individually or, more likely, jointly affect individual susceptibility to HPV16-associated OSCC, particularly SCCOP and never smokers. Validation of our findings is warranted.

O05.5 A Longitudinal Study of the Vaginal Microbiota and HPV Detection

BackgroundThe vaginal microbiota can be clustered into six community state types (CSTs): 4 are dominated by Lactobacillus iners, L. crispatus, L. gasseri, L. jensenni, and 2 lack significant numbers of...

I Have HPV. Does That Mean That My Husband Cheated on Me? Answering Women's Questions About HPV

<h2>Paper Presentation</h2><h3>Background</h3> The purpose of this presentation is to educate nurses about the most current evidence‐based research findings regarding human papillomavirus (HPV). Many healthcare professionals are not current on the research associated with HPV. Thus, they are uncomfortable discussing it with patients. HPV is the primary cause of cervical cancer, genital warts, and cancers of the vulva, vagina, penis, anus, and oropharynx. Most individuals have never heard about HPV and its association to cervical cancer. Cervical cancer is preventable, and it is the responsibility of the healthcare team to empower patients with scientifically accurate information regarding HPV prevention. <h3>Case</h3> A newly married, 29‐year‐old, White, healthy female presented to the clinic to obtain her ASCUS/+HPV Pap smear results. Upon receiving the diagnosis of HPV, with tears in her eyes the patient responded to the nurse practitioner, "I have HPV. Does that mean that my husband cheated on me?" The patient was educated about transmission, clearance, and risks of HPV. Her question was answered by the nurse practitioner based on evidence‐based practice literature. A new onset of HPV does not necessarily mean that infidelity has taken place. Research confirms that a healthy immune system can clear HPV in 12 to 24 months from the time of transmission. HPV persistence can occur for up to 10 to 15 years; therefore, it is possible for a partner to have contracted HPV from a previous partner and transmit it to a current partner. It is also possible the patient's partner recently cheated on her; research confirms both possibilities. <h3>Conclusion</h3> Research literature indicates that scientifically current HPV skill‐building and informational resources are needed to help healthcare providers meet the concerns of their patients. HPV research has rapidly progressed; however, public knowledge has not kept pace with the scientific advances. Female patients are seeking specific information about HPV from their healthcare teams. This is why it is important for healthcare professionals, including nurse practitioners and nurses, to stay informed about the most recent and scientifically accurate HPV research.

Polymorphism in the promoter region of the Toll-like receptor 9 gene and cervical human papillomavirus infection

Polymorphism in the Toll-like receptor (TLR) 9 gene has been shown to have a significant role in some diseases; however, little is known about its possible role in the natural history of human papillomavirus (HPV) infections. We investigated the association between a single-nucleotide polymorphism (SNP) (rs5743836) in the promoter region of TLR9 (T1237C) and type-specific HPV infections. Specimens were derived from a cohort of 2462 women enrolled in the Ludwig-McGill Cohort Study. We randomly selected 500 women who had a cervical HPV infection detected at least once during the study as cases. We defined two control groups: (i) a random sample of 300 women who always tested HPV negative, and (ii) a sample of 234 women who were always HPV negative but had a minimum of ten visits during the study. TLR9 genotyping was performed using bidirectional PCR amplification of specific alleles. Irrespective of group, the WT homozygous TLR9 genotype (TT) was the most common form, followed by the heterozygous (TC) and the mutant homozygous (CC) forms. There were no consistent associations between polymorphism and infection risk, either overall or by type or species. Likewise, there were no consistently significant associations between polymorphism and HPV clearance or persistence. We concluded that this polymorphism in the promoter region of TLR9 gene does not seem to have a mediating role in the natural history of the HPV infection.

Human papillomavirus type 16 viral load measurement as a predictor of infection clearance

Viral load measurements may predict whether human papillomavirus (HPV) type 16 infections may become persistent and eventually lead to cervical lesions. Today, multiple PCR methods exist to estimate viral load. We tested three protocols to investigate viral load as a predictor of HPV clearance. We measured viral load in 418 HPV16-positive cervical smears from 224 women participating in the Ludwig-McGill Cohort Study by low-stringency PCR (LS-PCR) using consensus L1 primers targeting over 40 known HPV types, and quantitative real-time PCR (qRT-PCR) targeting the HPV16 E6 and L1 genes. HPV16 clearance was determined by MY09/11 and PGMY PCR testing on repeated smears collected over 5 years. Correlation between viral load measurements by qRT-PCR (E6 versus L1) was excellent (Spearman's rank correlation, ρ = 0.88), but decreased for L1 qRT-PCR versus LS-PCR (ρ = 0.61). Viral load by LS-PCR was higher for HPV16 and related types independently of other concurrent HPV infections. Median duration of infection was longer for smears with high copy number by all three PCR protocols (log rank P<0.05). Viral load is inversely related to HPV16 clearance independently of concurrent HPV infections and PCR protocol.

Consistent Condom Use Reduces the Genital Human Papillomavirus Burden Among High-Risk Men: The HPV Infection in Men Study

Data supporting the efficacy of condoms against human papillomavirus (HPV) infection in males are limited. Therefore, we examined the effect of consistent condom use on genital HPV acquisition and duration of infection. A prospective analysis was conducted within the HPV Infection in Men Study, a multinational HPV cohort study. Men who were recently sexually active (n = 3323) were stratified on the basis of sexual risk behaviors and partnerships. Using Cox proportional hazards regression, type-specific incidence of HPV infection and clearance were modeled for each risk group to assess independent associations with condom use. The risk of HPV acquisition was 2-fold lower among men with no steady sex partner who always used condoms, compared with those who never used condoms (hazard ratio, 0.54), after adjustment for country, age, race, education duration, smoking, alcohol, and number of recent sex partners. The probability of clearing an oncogenic HPV infection was 30% higher among nonmonogamous men who always used condoms with nonsteady sex partners, compared with men who never used condoms (hazard ratio, 1.29), after adjustment for country, age, race, education duration, marital status, smoking, alcohol, and number of recent sex partners. No protective effects of condom use were observed among monogamous men. Condoms should be promoted in combination with HPV vaccination to prevent HPV infection in men.

Associations between human herpesvirus-6, human papillomavirus and cervical cancer

Cervical cancer (CxCa) is the second most common cancer among women globally. Human papillomavirus (HPV) infection is thought to be a necessary, but not sufficient, causal factor in CxCa development. Why some women are able to clear HPV infection with no adverse effects, whereas others develop cancer, remains unclear. HHV-6 has demonstrated transformative abilities and has been shown to be present in the genital tract. However, based on the current evidence, we cannot conclude that HHV-6 is a co-factor in HPV-associated carcinogenesis. Nonetheless, future research is warranted because of several crucial gaps in the literature.

Change in cytokines in patients with warts after contact immunotherapy with squaric acid dibutylester

A wart is a skin lesion caused by infection with human papillomavirus (HPV). Contact immunotherapy is one of the many therapeutic options that have been used to treat warts; however, the effectiveness of contact immunotherapy differs from patient to patient, and the cause of this variation in clinical response is unclear. To assess cytokine changes in patients after contact immunotherapy with squaric acid dibutylester (SADBE). In total, 21 patients with warts and 9 healthy control subjects were enrolled in the study. The frequencies of CD3+ T cells expressing interleukin (IL)-4, IL-10, IL-12, tumour necrosis factor-α and interferon-γ were measured by flow cytometry analysis of peripheral blood at baseline in both patients and controls, and after SADBE treatment in patients. Lower expression of IL-4 and higher expression of IL-12 in CD3+ T cells were found in patients compared with controls. The percentage of CD3+/IL-4+ T cells significantly increased after contact immunotherapy in all responders, but was significantly higher in those with an excellent response, who also had a significantly higher percentage of CD3+/IL-10+ T cells. The patients with an excellent response also had a significant decrease in the percentage of CD3+/IL-12+ T cells, and the percentage of CD3+/IL-4+ T cells normalized. Response to contact immunotherapy can vary depending on the types of cytokine changes produced by treatment. An excessive shift to a Th2 pattern and increased IL-10 production after contact immunotherapy may hinder clearance of HPV.

Cervical cytokines and clearance of incident human papillomavirus infection: Hawaii HPV cohort study

Mechanisms for the control and resolution of human papillomavirus (HPV) infection of the cervix include the local production of cytokines, which control recruitment and function of cells integral to pathogen control. We established a cohort of women for long-term follow-up to examine the mucosal expression of antiviral (IFN-α2), Type-1 (IFN-γ, IL-12), regulatory (IL-10), and proinflammatory (IL-1α, IL-1β, IL-6, IL-8, MIP-1α, and TNF) cytokines in association with the clearance of incident cervical HPV infection. Interviews and specimens for HPV DNA analysis and cytokine protein measurement were obtained at baseline and at 4-month intervals. A Cox proportional hazards model was used to study the relationship between clearance of 107 high-risk and 111 low-risk incident HPV infections and cytokine levels among 154 women. Positive changes from baseline levels of IL-10, IL-12, MIP-1α, and TNF were associated with significantly longer times to type-specific HPV clearance. Inverse trends in the hazard ratios associated with clearance of high-risk HPV infections were monotonic and significant for IL-12 (ptrend = 0.02) and TNF (ptrend = 0.02); the likelihood of high-risk HPV clearance was reduced by 65% and 67%, respectively, among women in the highest as compared with the lowest quartile of change from baseline. Our results suggest that in women with a nontransient cervical HPV infection, proinflammatory, Type-1, and regulatory cytokines are elevated, underscoring the long-term commitment of local immune mediators to viral eradication.