Human Papillomavirus Clearance Research Articles

Effectiveness of the thermal ablation in the treatment of human papillomavirus infection and cervical intraepithelial neoplasia in Chinese women

Objective: To evaluate the effectiveness of thermal ablation in the treatment of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) in Chinese women. Methods: The high-risk HPV-positive women aged 20-65 who were detected through a cervical cancer screening project implemented in three rural sites (Etuoke counties in Inner Mongolia, Xiangyuan and Yangcheng counties in Shanxi Province) and one urban site (Shenzhen) in China were included in this prospective study. Follow up evaluation was performed on HPV positive women who underwent thermal ablation (n=166) as well as received no treatment (n=2 716) in cervical cancer screening program. For women with thermal ablation treatment, HPV test and cytology were used for follow-up with the interval of 6 months or longer after treatment. For women without treatment, HPV test was used for annual follow-up. Women with positive results in either of the HPV tests or abnormal cytology were referred for a colposcopy or biopsy if necessary. The HPV clearance rate and the cure rate of CIN were compared between the two groups. Results: A total of 152 women treated with thermal ablation and 2 539 women without treatment reported for follow-up evaluation with the age M(Q1, Q3) of 42 (36, 48) and 47 (41, 54) years old, and the median time to follow-up time of 23.4 (12.4, 24.5) and 23.5 (12.4, 24.0)months, respectively. The HPV clearance rate in women undergoing thermal ablation was significantly higher than that in women with no treatment (73.0% vs 46.1%, P<0.001). The HPV16, HPV52 and HPV58 clearance rates among women receiving thermal ablation were higher than that in women without treatment with the OR (95%CI) of 2.8 (1.3-6.1), 3.2 (1.3-7.9) and 5.8 (2.1-15.6). For women with histologically confirmed CIN at baseline, cure rates were 77.4%(n=72) for thermal ablation. Cure rates of the thermal ablation were 81.0%(n=47) for CIN grade one (CIN1) and 71.4% (n=25) for CIN grade two or worse (CIN2+). Conclusions: Thermal ablation is effective to clear the HPV infection as well as to treat CIN. Particularly for the HPV genotypes with the paramount attributable proportion to cervical cancer and precancerous in China, the HPV clearance rate was significantly higher than that reported in the women without treatment.

Persistence and clearance of high-risk human papillomavirus and cervical dysplasia at 1year in women living with human immunodeficiency virus: a prospective cohort study.

Evaluate 1-year outcomes of cervical cancer screening and treatment using primary high-risk human papillomavirus (HPV) testing in women living with human immunodeficiency virus (HIV). Prospective cohort study. HIV treatment centre in Botswana. Women living with HIV. Participants underwent cervical cancer screening with high-risk HPV testing and triage evaluation at baseline and 1-year follow up. Excisional treatment was offered as indicated. Histopathology was the reference standard. Persistence, clearance and incidence of high-risk HPV infection; and persistence, progression, regression, cure and incidence of cervical dysplasia. Among 300 women screened at baseline, 237 attended follow up (79%). High-risk HPV positivity significantly decreased from 28% at baseline to 20% at 1year (P=0.02). High-risk HPV persistence was 46% and clearance was 54%; incidence was high at 9%. Prevalence of cervical intraepithelial neoplasia Grade 2 (CIN2) or higher was most common in participants with incident high-risk HPV (53%). CIN2 or higher was also common in those with persistent high-risk HPV (32%) and even in those who cleared high-risk HPV (30%). Of the high-risk HPV-positive participants at baseline with <CIN2, 40% progressed to CIN2 or higher at follow up. The high incidence of high-risk HPV and high-grade cervical dysplasia in women living with HIV after one round of high-risk HPV-based screening and treatment raises concern about the rate of progression of high-risk HPV infection to dysplasia. Persistent disease is common. Caution in spacing cervical cancer screening intervals using high-risk HPV testing in women living with HIV is warranted. High incidence and persistence of HPV and CIN2+ in women living with HIV 1year after screening and treatment.

Cohort profile: indigenous human papillomavirus and oropharyngeal squamous cell carcinoma study - a prospective longitudinal cohort

PurposeOur aims are to: (1) estimate prevalence, incidence, clearance and persistence of oral human papillomavirus (HPV) infection among Indigenous Australians; (2) identify risk factors associated with oropharyngeal squamous cell carcinoma...

Male Circumcision Reduces Penile HPV Incidence and Persistence: A Randomized Controlled Trial in Kenya.

Male circumcision reduces the risk of human immunodeficiency virus infection in men. We assessed the effect of male circumcision on the incidence and natural history of human papillomavirus (HPV) in a randomized clinical trial in Kisumu, Kenya. Sexually active, 18- to 24-year-old men provided penile exfoliated cells for HPV DNA testing every 6 months for 2 years. HPV DNA was detected via GP5+/6+ PCR in glans/coronal sulcus and in shaft samples. HPV incidence and persistence were assessed by intent-to-treat analyses. A total of 2,193 men participated (1,096 randomized to circumcision; 1,097 controls). HPV prevalence was 50% at baseline for both groups and dropped to 23.7% at 24 months in the circumcision group, and 41.0% in control group. Incident infection of any HPV type over 24 months was lower among men in the circumcision group than in the control group [HR = 0.61; 95% confidence interval (CI), 0.52-0.72]. Clearance rate of any HPV infection over 24 months was higher in the circumcision group than in the control group (HR = 1.87; 95% CI, 1.49-2.34). Lower HPV point-prevalence, lower HPV incidence, and higher HPV clearance in the circumcision group were observed in glans but not in shaft samples. Male circumcision reduced the risk of HPV acquisition and reinfection, and increased HPV clearance in the glans. Providing voluntary, safe, and affordable male circumcision should help reduce HPV infections in men, and consequently, HPV-associated disease in their partners.

Incidence and Clearance of Penile High-Risk Human Papillomavirus Infection and Their Determinants Among HIV-Negative Men Who Have Sex With Men.

Men who have sex with men (MSM) are at increased risk of anogenital human papillomavirus (HPV) infections. We aimed to assess the incidence and clearance of penile high-risk HPV (hrHPV) infections and their determinants among HIV-negative MSM living in the Netherlands. Between 2010 and 2015, HIV-negative MSM were semiannually tested for penile HPV and completed detailed questionnaires on health and sexual behavior. Self-collected penile swabs were tested for HPV DNA using SPF10-PCR DEIA/LiPA25 system. Type-specific hrHPV incidence (IR) and clearance rates (CR) were calculated for 12 hrHPV types (HPV-16, HPV-18, HPV-31, HPV-33, HPV-35, HPV-39, HPV-45, HPV-51, HPV-52, HPV-56, HPV-58, and HPV-59). Determinants of incidence and clearance of HPV-16 and HPV-18, separately, and combined 7 hrHPV types covered by the nonavalent vaccine were assessed by Poisson regression using generalized estimating equations for combined hrHPV types. We included 638 HIV-negative MSM, with a median age of 38 (interquartile range, 33-43) years. HPV-16 had an IR of 4.9/1000 person-months of observation at risk (PMO; 95% confidence interval [95% CI], 3.8-6.3) and CR of 90.6/1000 PMO (95% CI, 60.7-135.1). The IR and CR of HPV-18 were 3.4/1000 PMO (95% CI, 2.5-4.5) and 119.2/1000 PMO (95% CI, 76.9-184.8), respectively. Age and condom use during insertive anal sex were not associated with hrHPV incidence, whereas high number of recent sex partners was. The relatively high IR and low CR of penile HPV-16 and HPV-18 among HIV-negative MSM correlates with their high prevalence and oncogenic potential. Incident HPV infections were associated with recent sexual risk behavior.

Efficacy of a Coriolus versicolor-Based Vaginal Gel in Women With Human Papillomavirus-Dependent Cervical Lesions: The PALOMA Study.

ObjectiveThe aim of the study was to evaluate the efficacy of Papilocare, a Coriolus versicolor–based vaginal gel, in repairing human papillomavirus (HPV)-related low-grade cervical lesions.MethodsThe study is a multicenter, open-label, randomized, parallel-group, watchful waiting approach-controlled trial involving 91 HPV-positive women with low-grade Pap smear alterations and consistent colposcopy.ResultsThe percentage of patients with normal Pap smear and concordant colposcopy 3 and 6 months after receiving treatment (78.0% and 84.9%) was significantly higher than without treatment (54.8% and 64.5%), especially in high-risk HPV patients (79.5% and 87.8% vs 52.0% and 56.0%). At 6-month visit, overall HPV clearance was achieved by a greater number of patients receiving treatment (59.6%) compared with those without treatment (41.9%), especially high-risk HPV ones (62.5% vs 40.0%). The cervical re-epithelization score was significantly higher with treatment (mean = 4.5) than without (mean = 4.1). Compared with baseline, perceived stress decreased in the treatment group (from 21.1 to 19.0) and increased in the control group (from 17.7 to 20.7). A total of 7 possible or probable treatment-related adverse events were reported, most of them (n = 6) being mild or moderate in severity.ConclusionsTreatment with Papilocare has demonstrated a better clinical benefit than the conventional watchful waiting approach in clinical practice for total and high-risk HPV patients in terms of its efficacy to treat HPV-related cervical lesions and to clear all HPV strains after a single 6-month period. It has demonstrated an adequate safety and tolerability and confers additional benefits such as higher re-epithelization, stress reduction, and high treatment adherence.

Correlation of the ALA-PDT Treatment Efficacy and the HPV Genotype Profile of Genital Warts after Cryotherapy Failure and Podophyllotoxin Therapy in Male Patients.

Background: Genital warts are the manifestation of the human papillomavirus (HPV) infection, which may last for weeks or months before the clinical presentation. The primary aim of the study was the correlation of the DNA HPV genotypes eradication with the treatment response in male patients with persistent genital warts. Methods: Twenty-one male patients (age range: 22–58) after failure of cryotherapy and podophyllotoxin treatment were enrolled in the study. Genetic tests (Real Time - PCR method) analyzed the presence of DNA-HPV before and 6 months after four sessions (4 weeks apart) of photodynamic therapy with 5-aminolaevulinic acid (ALA-PDT). The treatment efficacy was evaluated before each PDT session and at the end of the study. Results: The single HPV DNA type was present in 15/21 of the patients (13/15 HPV6). The high-risk HPV types were found in 8/21 subjects, of which 6/8 had several types. Six months after four sessions of PDT, complete response was found in 16/21 (76.19%; p = 0.0007) of patients, and DNA HPV clearance was found in 66.67% (p = 0.03). The eradication rate differed among patients with primary low-risk and high-risk HPV types—76.92% (10/13; p = 0.0003) and 50% (4/8; p = 0.05) respectively. Conclusion: ALA-PDT is an effective treatment even after the failure of previous modalities. The persistence of clinical lesions and high oncological risk HPV types should be an indication for treatment prolongation.

Human papillomavirus persistence or clearance after infection in reproductive age. What is the status? Review of the literature and new data of a vaginal gel containing silicate dioxide, citric acid, and selenite.

Cervical cancer, the third most common cancer in women, is caused in nearly all cases by a persistent infection with high-risk types of the human papillomavirus. Although human papillomavirus infections are 80%–90% transient and disappear spontaneously within 24 months, human papillomavirus infections that remain are at risk of developing cervical lesions. Different therapeutical approaches have been tested to promote the regression of low-grade lesions or prevent progression. They include the application of 5-fluorouracil, curcumin, imiquimod, interferons, Vitamin D, and others. Also, the effect of probiotics and vaginal therapy with carboxy-methyl-beta glucan was assessed. Review of the literature and presentation of the last study data are presented. Clearance of high-risk human papillomavirus seemed to be promoted by treatment with a new vaginal gel containing a highly disperse SiO2 and an anti-oxidative combination of citric acid and sodium. This gel showed, after 6 months, an improvement of cytological Pap findings (ASC-US, LSIL, ASC-H, or HSIL) in 80.9% of the participants. Similarly, there was a clearing of hr-human papillomavirus in 53% of cases after 3 months of gel administration. The percentage increased slightly in the non-treated control group from 78.3% at baseline to 83% after 3 months. The percentage of patients who were tested positive for p16/Ki67 reduced from 75% at baseline to 5.3% in the treatment group after 6 months, while the percentage decreased only slightly in the non-treated group (baseline: 91.5%; 6 months: 75.2%). The examined vaginal gel may support the healing of conspicuous cytological findings (ASC-US, LSIL, ASC-H, or HSIL) and clearance of hr-human papillomavirus positive results.

Clinical study on black raspberry extract on the negative rate and effectiveness of patients with persistent human papilloma virus infection

To investigate the negative rate and effectiveness of black raspberry extract in clearing persistent infection with human papilloma virus ( HPV), t hree hundred patients are included in the randomized, double blind, placebo controlled human trial for multicenter indication . The distribution ratio of the test ed group versus the control group is 2: 1 and the subject patients were given a preparation in the vagina before bed every other day, each dose was 3 g containing black raspberry extract (tested group) or placebo (control group). SPSS 20.0 was used for statistical analysis. Differences between groups were analyzed by the Rank Sum method or Chi square method. The results showed that 191 subjects in the tested group completed the trial , of which 139 subjects ( 72.8% were identified to have an effective clear ance of HPV ; 95 subjects in the control group completed the trial , of which only 15 subjects ( 15.8% were identified to have effective clearance of HPV. The difference between the two groups was statistically significant (  2 = P 0.001 ). The HPV viral load of the tested group was decreased from 224.7 RLU/CO to 88.6 RLU/CO whereas HPV viral load of the control group was ascend ed from 218.4 RLU/CO to 266.1 RLU/CO Thus , the present clinical observation suggested that b lack raspberry extract may be a potential candidate in targeting persistent infection with HPV.

Incidence, persistence and clearance of cervical human papillomavirus among women in Guangdong, China 2007–2018: A retrospective cohort study

BackgroundPrevious studies showed the incidence, persistence and clearance of cervical human papillomavirus (HPV) among women varies from regions. There is no study on dynamic changes of HPV infection among women in Guangdong. MethodsIt is a retrospective cohort study that included gynecological outpatients aged ≥15 years and retested for HPV within 24 months in Guangdong Women and Children Hospital to estimate HPV incidence, persistence and clearance. Outcomes were estimated through the proportion of HPV incidence, persistence and clearance in HPV-negative or HPV-positive women. Moreover, we examined HPV incidence, persistence and clearance among women who retested in four calendar periods: 0–6, 6–12, 12–18, 18–24 months after the first test. Results33,328 gynecological outpatients were included in our study. Incidence rates of any HPV, high-risk (HR) HPV and low-risk (LR) HPV were 10.58%, 8.68% and 4.83%. The most common incident HR HPV were HPV52 (2.69%), HPV16 (1.23%) and HPV58 (1.23%). Persistence rates of any HPV, HR HPV and LR HPV were 47.55%, 42.77% and 33.88%. HPV52 (42.33%), HPV58 (40.74%) and HPV68 (32.36%) were commonly found persistent types. And clearance rates of any HPV, HR HPV and LR HPV were 52.44%, 57.23% and 66.12%.The lowest clearance rates were observed for HPV52 (57.67%), HPV68 (67.64%) and HPV39 (68.56%). HPV incidence and persistence were higher among women aged 15–19 years and ≥55 years. HPV incidence and persistence were found higher among women who retested within 6 months than others in other periods. ConclusionsHPV52, 58, 68, and 39 were the more likely to cause incident and persistent infection, and less likely to be cleared among women in Guangdong. HPV incidence and persistent infection were higher among women aged both younger and older women compared to middle aged women. HPV retesting period may impact the detection of HPV incidence, persistence and clearance.

Association of Serum 25-Hydroxyvitamin D With Prevalence, Incidence, and Clearance of Vaginal HPV Infection in Young Women

We assessed the association between serum 25-hydroxyvitamin D levels and genital human papillomavirus (HPV) prevalence, incidence, and clearance among female participants in the HPV Infection and Transmission among Couples through Heterosexual activity (HITCH) Cohort Study. We genotyped HPV DNA in vaginal samples and quantified baseline serum 25-hydroxyvitamin D levels using Roche's Linear Array and Total vitamin D assay, respectively. We used logistic and Cox proportional hazards models, respectively, to estimate adjusted odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs). There was no association between vitamin D levels (every 10-ng/mL increase) at baseline and HPV prevalence (OR, 0.88; 95% CI, .73-1.03) or incidence (HR, 0.88; 95% CI, .73-1.06), but we observed a modest negative association with HPV clearance (HR, 0.76; 95% CI, .60-.96). Vitamin D levels <30 ng/mL, compared with those ≥30 ng/mL, were not associated with HPV prevalence (OR, 0.98; 95% CI, .57-1.69) or incidence (HR, .87; 95% CI, .50-1.43), but they were associated with a marginally significant increased clearance (OR, 2.14; 95% CI, .99-4.64). We observed consistent results with restricted cubic spline modeling of vitamin D levels and clinically defined categories. HPV type-specific analyses accounting for multiple HPV infections per participant showed no association between vitamin D levels and all study outcomes. This study provided no evidence of an association between low vitamin D levels and increased HPV prevalence, acquisition, or clearance.

Clearance of human papillomavirus infection in patients with cervical intraepithelial neoplasia: A systemic review and meta-analysis.

Background:There are currently no available standard drugs treating human papillomavirus (HPV) infection, especially for patients with low-grade cervical lesion. Several therapies are explored but the results are inconclusive. The objective of this study was to evaluate the efficacy of reported non-invasive treatments in patients with HPV infection and cervical lesions by meta-analysis.Methods:A comprehensive search of prospective and randomized studies published from April 2000 to April 2020 was conducted in electronic databases. The statistical analyses of the pooled risk ratios (RRs) and the corresponding 95% confidence intervals (95% CIs) were performed using the Revman 5.2 software.Results:Twelve articles including 12 randomized controlled studies and 1 prospective controlled randomized pilot study were enrolled. Therapeutic medications included biological and herbal regimen, interferon regimen and probiotics. The meta-analysis showed the experimental treatments had a statistically significant improvement in HPV clearance rate compared with the controls (RR = 0.71, 95% CI [0.63, 0.80], P < .00001); subgroup analyses stratified by regimen categories were consistent with results in the overall group. Treatment using biological and herbal regimen, interferon regimen or probiotics also resulted in a beneficial outcome in regression rate of cervical lesions compared with the controls (RR = 0.55, 95% CI [0.39, 0.79], P = .001). The trend was more favorable in the probiotics than that in the biological and herbal regimen (RR 0.48 vs 0.72).Conclusion:Treatment of biological and herbal regimen, interferon regimen and probiotics benefit patients who have HPV infection and cervical lesions. Both the clearance of HPV and regression of cervical lesions are significant. More studies with less heterogeneity are needed to draw a concrete conclusion.

Factors Associated With Persistence and Clearance of High-Risk Oral Human Papillomavirus (HPV) Among Participants in the HPV Infection in Men (HIM) Study.

BackgroundHuman papillomavirus (HPV)–attributable oropharyngeal cancer (HPV-OPC) incidence is increasing in many high-income countries among men. Factors associated with oral HPV persistence, the precursor of HPV-OPC, are unknown. Data from the HPV Infection in Men (HIM) Study, which followed participants >7 years, were utilized to examine rates of persistence and associated factors.MethodsOral gargle samples from 3095 HIM study participants were HPV genotyped using the SPF10 PCR-DEIA-LiPA25 assay (DDL Diagnostic Laboratory). Oral HPV persistence for individual and grouped high-risk HPV types among 184 men positive for any high-risk HPV at their oral baseline visit was assessed at 6-month intervals. Factors associated with grouped high-risk HPV/HPV16 persistence were examined using logistic regression. Kaplan-Meier curves were constructed to examine median time to HPV clearance overall, and by selected risk factors.ResultsAmong the 7 HPV vaccine types, HPV33 had the longest median duration (7.6 months) followed by HPV16 and HPV45 (6.4 months). 10–30% of oral high-risk HPV infections persisted ≥24 months. Six months’ persistence of oral high-risk HPV infections was positively associated with age and gingivitis and negatively with lifetime number of sexual partners, while 12 months’ persistence was only inversely associated with lifetime number of sexual partners. Oral HPV16 persistence was positively associated with baseline HPV16 L1 antibody status.ConclusionsEighteen percent of HPV16 infections persisted beyond 24 months, potentially conferring higher risk of HPV-OPC among these men. Older age appears to be an important factor associated with oral high-risk HPV persistence. More studies among healthy men are required to understand the progression of oral HPV infection to HPV-OPC.

Serum level of interleukin-22 in patients with cutaneous warts: A case-control study.

Warts are viral cutaneous infections caused by human papilloma virus (HPV), presented by verrucous growth over the skin surface. The immune response is considered to play a crucial role in HPV clearance. It depends on intact cellular immunity including natural killer (NK) cell and cytotoxic T cells. It has been clarified that T-helper (Th) 1 cytokines (interleukin (IL)-2, interferon-γ, and tumor necrosis factor-a) and IL-17 are involved in HPV clearance. IL-22 is one of IL-10 family of cytokines produced by NK cells, Th1, Th17, and Th22 cells. In the skin, IL-22 reduces keratinocyte cornification and enhances keratinocyte production of antimicrobial peptides. IL-22 overexpression has been demonstrated in various viral infections and skin inflammatory disorders. The aim of this study was to assess serum levels of IL-22 in patients with warts and its association with their different clinical characteristics. The study included 20 patients with warts and 20 control subjects. Serum concentration of IL-22 was measured by enzyme-linked immune sorbent assay. Serum levels of IL-22 were significantly higher in patients with warts than in control subjects (P<.001). The levels were significantly higher in patients with recurrent warts after prior treatment than in patients with first-time warts (P=.007). Moreover, a significant positive correlation was detected between serum levels of IL-22 and the number of warts (P=.017). Serum level of IL-22 was elevated in patients with warts. Thus, IL-22 may have a crucial role in the antiviral immune response against this infection.

Oral human papillomavirus infection in HIV-infected and HIV-uninfected MSM: the OHMAR prospective cohort study

ObjectiveWe aimed to assess incidence and clearance of oral human papillomavirus (HPV) infection and the respective risk factors in HIV-infected and uninfected men who have sex with men (MSM).MethodsOral rinse...

Efficacy of 5-aminolevulinic acid and LED photodynamic therapy in cervical intraepithelial neoplasia: A clinical trial.

5-Aminolaevulinic acid (5ALA) is a precursor of the strong sensitizer protoporphyrin IX (PpIX) in the heme synthesis pathway. We conducted aclinical trial designed to evaluate the efficacy and safety of 5ALA photodynamic therapy (PDT) using a light-emitting diode (LED) in patients with cervical intraepithelial neoplasia (CIN). Data for 51 CIN patients who underwent 5ALA-PDT between 2012 and 2017 were prospectively analysed. After a 20 % 5ALA jelly formulation was topically applied to the cervix, the region was irradiated with red light at approximately 633 nm to excite PpIX for treatment. We estimated outcomes by cytology, pathology, and human papilloma virus (HPV) testing after PDT. Patients underwent two PDT sessions at one-week intervals during outpatient treatment and achieved favourable results without photosensitivity and severe adverse events. Over a long follow-up period, 96.1 % of all patients showed some positive effects, including approximately 70 % with a complete response (CR), 10 % with a partial response, and 15 % with downgrades. The HPV clearance rate in patients with CR was 79.4 %. Recurrence occurred in five patients who mostly remained HPV-positive after PDT. Based on our study, topical 5ALA-PDT using an LED light source potentially represents a safe treatment for CIN on an outpatient basis.

Cervical-Vaginal Microbiome and Associated Cytokine Profiles in a Prospective Study of HPV 16 Acquisition, Persistence, and Clearance.

Persistent human papillomavirus (HPV) infections is necessary for the development of cervical cancers. Consequently, understanding the biologic mechanisms resulting in clearance is key in cancer prevention. Similar to other mucosal sites, it is expected that the local microbiome plays a significant role in shaping the immune response responsible for HPV clearance. Using cervical wash repository samples from a prospective study of HPV in women, this study investigates the microbiome and its associated inflammatory milieu during HPV 16 pre-acquisition, persistence and clearance states. For comparison, samples from women with no history of HPV ever during the study period were selected. We showed that 9 of 13 inflammatory cytokines were found to be significantly increased in the immediate post-clearance visit compared to the pre-acquisition or infection visits. Gardnerella vaginalis was associated with higher levels of inflammatory cytokines. Women with no history of HPV infection had similar cytokine profiles as those with HPV 16 post-clearance. This in vivo study documented an immune response shortly after HPV 16 clearance. G. vaginalis appeared to be involved in shaping this immune response. The appearance of G. vaginalis may have resulted from a shift from anti-microbial to anti-viral immune response with loss of bacterial control. The similar high levels of cytokines seen in women with no history of HPV suggest that a certain level of inflammatory surveillance is required to maintain an HPV negative state. This data may inform therapies such as probiotics or pro-inflammatory agents for treatment of persistent HPV.

Incidence and clearance of penile human papillomavirus infection among circumcised Kenyan men.

Prospective data are limited on human papillomavirus (HPV) acquisition and clearance among circumcised men from resource-limited geographical regions, particularly Africa. The goal of this study was to estimate incidence and clearance of type-specific genital HPV infection in men. Penile exfoliated cell specimens were collected from the glans/coronal sulcus and shaft of 1,037 circumcised Kenyan men at baseline and 6-, 12- and 18-month follow-up visits between 2003-2007. Specimens were tested with GP5+/6+ PCR to detect 44 HPV types. The median age of participants at baseline was 21 years (range 18-28). The 12- and 18-month incidence rates (IRs) for any HPV were 34.9/100 person-years (95% confidence interval [CI]: 31.2-39.0) and 36.4/100 person-years (95% CI: 32.9-40.2), respectively. The 18-month cumulative risk for high-risk HPV was 30% compared to 16% for low-risk HPV. Cumulative risk was not associated with age or anatomical site. The estimated probability of any HPV infection clearing by 12 months was 0.92. Time until HPV clearance was not associated with age, anatomical site, or whether HPV infection type was high-risk or low-risk. HPV IRs among circumcised men in this study were comparable to other circumcised populations.

Predictors of Human papillomavirus (HPV) persistence after treatment of high grade cervical lesions; does cervical cytology have any prognostic value in primary HPV screening?

ObjectiveThis study aimed to determine the factors associated with Human Papillomavirus (HPV) persistence in women undergoing cervical excision for pre-invasive lesions, after they have been referred from a primary HPV screening program. MethodsA retrospective study design involving patients who were treated at a Cervical Disease Screening and Treatment Unit, in a university hospital setting. After initial treatment, cervical HPV infection status was analyzed at the sixth month, first year and then subsequently after the second year. ResultsTotally, 395 patients who were diagnosed with pre-invasive cervical lesions and who subsequently undergone cervical excision were identified. In the first-year visit after cervical excision, HPV 18 was cleared in almost all (95.8%) cases, followed by HPV 16 (69.9%) and other hrHPV types (65.6%). Available data documented that 88.6% of women reached clearance after the two-year follow-up. Univariate analysis revealed a significantly higher proportion of HPV clearance among women who were younger (p = 0.019), premenopausal (p = 0.002), and who had been found to have a negative cytology result on their initial Pap test (p = 0.018). However, only cervical cytology result remained as the independent predictor of HPV persistence on a multivariate logistic regression (OR 0.43; 95% CI 0.21–0.87; p = 0.019). ConclusionsA low risk of HPV persistence was found among every HPV genotype in women undergoing cervical excision for pre-invasive cervical lesions. Initial cervical cytology result was the only independent predictor of HPV clearance during surveillance, which indicates the prognostic value of Pap test in primary HPV screening.

P16/ki67 and E6/E7 mRNA Accuracy and Prognostic Value in Triaging HPV DNA-Positive Women.

The study presents cross-sectional accuracy of E6 and E7 (E6/E7) mRNA detection and p16/ki67 dual staining, alone or in combination with cytology and human papillomavirus (HPV)16/18 genotyping, as a triage test in HPV DNA-positive women and their impact on cervical intraepithelial neoplasia (CIN2+) overdiagnosis. Women aged 25-64 years were recruited. HPV DNA-positive women were triaged with cytology and tested for E6/E7 mRNA and p16/ki67. Cytology positive women were referred to colposcopy, and negatives were randomly assigned to immediate colposcopy or to 1-year HPV retesting. Lesions found within 24 months since recruitment were included. All P values were 2-sided. 40 509 women were recruited, and 3147 (7.8%) tested HPV DNA positive; 174 CIN2+ were found: sensitivity was 61.0% (95% confidence interval [CI] = 53.6 to 68.0), 94.4% (95% CI = 89.1 to 97.3), and 75.2% (95% CI = 68.1 to 81.6) for cytology, E6/E7 mRNA, and p16/ki67, respectively. Immediate referral was 25.6%, 66.8%, and 28.3%, respectively. Overall referral was 65.3%, 78.3%, and 63.3%, respectively. Cytology or p16/ki67, when combined with HPV16/18 typing, reached higher sensitivity with a small impact on referral. Among the 2306 HPV DNA-positive and cytology-negative women, relative CIN2+ detection in those randomly assigned at 1-year retesting vs immediate colposcopy suggests a -28% CIN2+ regression (95% CI = -57% to +20%); regression was higher in E6/E7 mRNA-negatives (Pinteraction = .29). HPV clearance at 1 year in E6/E7 mRNA and in p16/ki67 negative women was about 2 times higher than in positive women (Pinteraction < .001 for both). p16/ki67 showed good performance as a triage test. E6/E7 mRNA showed the highest sensitivity, at the price of too high a positivity rate to be efficient for triage. However, when negative, it showed a good prognostic value for clearance and CIN2+ regression.