Human Papillomavirus Clearance Research Articles

Comparing the effects of argon plasma coagulation and interferon therapy in patients with vaginal intraepithelial neoplasia: a single-center retrospective study

PurposeThis study aimed to evaluate the clinical efficacy and safety of argon plasma coagulation (APC) therapy and interferon therapy in patients with grade I and II vaginal intraepithelial neoplasia (VaIN).MethodsA total of 112 patients with VaIN were diagnosed via colposcopy-induced biopsy and classified into the APC group (n = 77) and interferon group (n = 35). Clinical data including age, grade, symptoms, historical or concomitant neoplasia of the lower genital tract, indications for hysterectomy, pregnancy history, cytology, human papillomavirus (HPV) subtype, treatment modalities, and clinical outcomes were analyzed, retrospectively. Complications and clinical outcomes were assessed at 6- and 12-month follow-ups.ResultsThere was no significant difference in the HPV clearance rate between the APC (53.42%) and interferon (33.33%) groups at 6 months after treatment. However, the 12-month follow-up of the APC group showed a significantly higher HPV clearance rate as compared to the interferon group (87.67% vs. 51.52%, P < 0.05). The APC group exhibited a significantly higher cure rate (79.22% vs. 40.0%) and lower persistence rate (12.99% vs. 37.14%) than the interferon group (P < 0.05). Adverse reaction analysis revealed that the primary reaction in the APC group was vaginal drainage, in contrast to the increased vaginal discharge in the interferon group; though the difference was significant (68.83% vs. 28.57%, P < 0.05), no serious complications were observed.ConclusionsTreatment with APC is a safe and more effective procedure against VaIN I and II, compared to interferon. APC may serve as a viable alternative to other physiotherapies.

Imiquimod Is Effective in Reducing Cervical Intraepithelial Neoplasia: A Systematic Review and Meta-Analysis.

Topical Imiquimod is an immune response modifier approved for the off-label use of vulvar intraepithelial neoplasia. We conducted this systematic review and meta-analysis to investigate the efficacy and safety of Imiquimod in treating cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV)-positive patients. The study was prospectively registered (CRD420222870) and involved a comprehensive systematic search of five medical databases on 10 October 2022. We included articles that assessed the use of Imiquimod in cervical dysplasia and HPV-positive patients. Pooled proportions, risk ratios (RRs), and corresponding 95% confidence intervals (CIs) were calculated using a random effects model to generate summary estimates. Statistical heterogeneity was assessed using I2 tested by the Cochran Q tests. Eight articles reported on 398 patients who received Imiquimod out of 672 patients. Among CIN-2-3 patients, we observed a pooled regression rate of 61% (CI: 0.46-0.75; I2: 77%). When compared, Imiquimod was inferior to conization (RR: 0.62; CI: 0.42-0.92; I2: 64%). The HPV clearance rate in women who completed Imiquimod treatment was 60% (CI: 0.31-0.81; I2: 57%). The majority of side effects reported were mild to moderate in severity. Our findings indicate that topical Imiquimod is safe and effective in reducing cervical intraepithelial neoplasia and promoting HPV clearance. However, it was found to be inferior compared to conization. Imiquimod could be considered a potential medication for high-grade CIN patients and should be incorporated into guidelines for treating cervical dysplasia.

Incidence, Clearance and Persistence of Penile High-Risk Human Papillomavirus among Rwandan Men who have Sex with Men

Abstract Background Little is known about penile high-risk HPV among MSM in low-and-middle income countries. We aimed to determine the incidence, clearance and persistence of penile hrHPV among Rwandan MSM. Methods We enrolled 350 MSM (345 with valid HPV results), aged ≥18 years, at each visit (6-12 months apart), we collected penile PreservCyt specimens and blood for HPV and HIV testing, socio-demographic and behavioral variables. HPV testing was performed using the Ampfire assay. Penile hrHPV incidence and clearance/1,000 person-months of follow-up (PMF), prevalent- and incident-persistence were computed and compared by HIV status. Results The mean age was 27.7 ± 6.7 years and 19.4% were living with HIV. Penile hrHPV incidence was 34.8 (95% CI: 29.1, 41.8)/1,000 PMF. HPV16 (11.7, CI 9.26, 14.9) and HPV59 (6.1, CI 4.52, 8.39) had the highest incidence rates. Prevalent- and incident-persistence were 47.5% and 46.6%, respectively. HPV66 (33.3%), HPV52 (30.8%) and HPV16 (29.2%) had the highest prevalent-persistence and HPV33 (53.8%), HPV31 (46.7%) and HPV16 (42.6%) the highest incident-persistence. No differences were found by HIV status except for HPV45 (higher in MSM with HIV). Conclusion We found high incidence and prevalent/incident-persistence of penile hrHPV among Rwandan MSM. This highlights the importance of preventive strategies for HPV-associated anogenital cancers.

Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147).

We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients. We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with self-applied vaginal suppositories containing imiquimod (Arm B) or imiquimod plus a 9vHPV (Arm C) versus clinical surveillance (Arm A). The main outcome was efficacy, defined as histologic regression to CIN1 or less. Secondary outcomes were HPV clearance and tolerability. Exploratory objectives included the comparison of cervical CD4/CD8 T-cell infiltration at baseline, mid-study, and posttreatment by flow cytometry among study arms. Of the 114 evaluable patients 77% and 23% harbored CIN2 and CIN3, respectively. Regression to CIN1 or less was observed in 95% of patients in the imiquimod group (Arm B) compared with 79% in the control/surveillance (Arm A); P = 0.043 and 84% in the imiquimod+9vHPV group (Arm C; P = 0.384 vs. Arm A). Neither of the treatment-arm differences from Arm A reached the prespecified α = 0.025 significance level. No significant differences were noted in the secondary outcome of rate of HPV clearance. The number of tissue-resident memory CD4/CD8 T cells in cytobrush samples demonstrated a >5-fold increase in Arm B/imiquimod when compared with Arm A/surveillance (P < 0.01). In contrast, there was no significant difference in T-cell responses among participants in Arm C when compared with Arm A. Imiquimod treatment was well tolerated. Although imiquimod induced a higher regression to CIN1 or less and significant increases in CD4/CD8 T cells infiltrating the cervix, it did not meet its prespecified statistical outcome for efficacy. A higher regression rate than expected was observed in the surveillance arm of this prospective trial. Future clinical trials with imiquimod targeting CIN3 patients are warranted.

Topical imiquimod treatment of residual or recurrent cervical intraepithelial neoplasia lesions (TOPIC-2): A randomised controlled trial.

To investigate the efficacy of imiquimod in women with residual or recurrent cervical intraepithelial neoplasia (rrCIN), compared with large loop excision of the transformation zone (LLETZ). Randomised controlled non-inferiority trial. One academic and one regional hospital in the Netherlands. Thirty-five women with rrCIN were included in the study between May 2016 and May 2021. Women were randomised to receive treatment with 5% imiquimod cream (12.5 mg) intravaginally (three times a week for a duration of 16 weeks) or a LLETZ procedure (standard treatment). The primary outcome was reduction to normal cytology at 6 months after starting treatment. Secondary outcomes were clearance of high-risk human papilloma virus (hr-HPV) in both groups and reduction to ≤CIN1 in the imiquimod group. Side effects were monitored. Treatment success was 33% (6/18) in the imiquimod group versus 100% (16/16) in the LLETZ group (P < 0.001), whereas HPV clearance was 22% (4/18) in the imiquimod group versus 88% (14/16) in the LLETZ group (P < 0.001). After the randomisation of 35 women, the futility of treatment with imiquimod was proven and the trial was prematurely finished. In the follow-up period, three patients remained without additional treatment, whereas all other patients underwent LLETZ, conisation or hysterectomy. In the LLETZ group none of the patients received additional treatment during 2 years of follow-up. This is the first randomised controlled trial to show that topical imiquimod has a significantly lower success rate in terms of reduction to normal cytology and hr-HPV clearance, compared with LLETZ, in women with rrCIN. Additionally, imiquimod has numerous side effects and after using imiquimod most women with rrCIN still required additional surgical treatment.

Evaluation of concordance between loop electrosurgical excisional procedure and cervical colposcopic biopsy results

To evaluate the results of loop electrosurgical excisional procedures (LEEP) with colposcopic biopsy results of patients who presented to our hospital for vaginal smears. The LEEP reports of patients who presented to our gynecology clinic between January 2015 and December 2020 were retrospectively evaluated. The data were obtained from electronic patient records and the department of medical pathology archives. A total of 579 patients were evaluated with a mean age of 38.05±6.17 years. Colposcopy-guided biopsy was not taken from 102 patients. The results of the remaining 477 (82.4%) patients were: no dysplasia (n=12; 2.1%), Cervical intraepithelial neoplasia-I (CIN-I) (n=99; 17.1%), CIN-II (n=111; 19.2%), CIN-III (n=248; 42.8%), and cancer (n=7; 1.2%). Completed excision was performed in 87.0% of the patients using LEEP, the lesion was positive at the surgical margins in 10.9%, and the lesion could not be completely excised in 2.1%. The complication rate after LEEP was 3.1% including pelvic pain (n=5; 0.9%) and bleeding (n=13; 2%). The histopathologic results of LEEP were: benign (n=50; 8.6%), CIN-I (n=110; 19.0%), CIN-II (n=89; 15.4%), CIN-III (n=280; 48.4%), cancer (n=7; 1.2%), and metaplasia (n=37; 6.4%). The concordance between colposcopic biopsy and LEEP results was 85.9% for CIN-I, 71.2% for CIN-II, 98.4% for CIN-III, and 85.7% for cancer diagnoses. LEEP is a simple minimally invasive method used in the treatment of CIN, with low persistence, recurrence, and complication rates and increased human papillomavirus clearance in most patients. Our results support the consistency of cervical colposcopic biopsy and LEEP results.

Incidence and clearance of cervical and anal high-risk human papillomavirus in kidney transplant recipients: Results from a Danish prospective clinical study

This study investigates the incidence and clearance of cervical and anal high-risk human papillomavirus (hrHPV) infection in kidney transplant recipients (KTRs) compared to immunocompetent controls. During 2016-2017, we enrolled 125 female KTRs and 125 female controls. Liquid-based cervical and anal cytology samples collected at enrollment and follow-up were tested for human papillomavirus (HPV) DNA using the CLART HPV2 test. All participants answered a questionnaire on lifestyle and sexual behavior at both examinations. KTRs had an increased age-adjusted risk of incident cervical hrHPV infection compared to controls (hazard ratio [HR] = 3.6, 95% CI = 1.2-11.2). Probability of cervical hrHPV clearance at 18 months was lower among KTRs (8.3%) than controls (66.7%). There was no statistically significant difference in anal hrHPV incidence between KTRs and controls (HR = 0.9, 95% CI = 0.4-2.0). Clearance of anal hrHPV was similar between KTRs and controls at 18 months. During the total follow-up, a lower anal hrHPV clearance, although not statistically significant, was observed among KTRs (HR = 0.3, 95% CI = 0.06-1.2). KTRs had higher incidence of cervical hrHPV and lower probability of clearance, especially of cervical hrHPV infections, than controls. Our findings support that KTRs are at increased risk of HPV infection and point to the need for targeted HPV prevention strategies, such as cervical cancer screening.

Human papillomavirus prevalence and dynamics: Insights from a 5-year population-based study in Jeddah, Kingdom of Saudi Arabia.

To estimate the prevalence and dynamics of human papillomavirus (HPV) infection, over a 5-year period, among Saudi women. A 2-phase, population-based study combining cross-sectional and cohort designs was carried out with 5360 ever-married women aged 30-65 from Jeddah, Saudi Arabia, between 2013 and 2018. Participants were enrolled in a designated screening program and screened using the hybrid capture 2 HPV test. Women testing positive for HPV were followed up after one year to estimate the HPV clearance rate, while those testing negative had a follow-up after 5 years to assess new HPV infections. Factors associated with HPV positivity and clearance, including sociodemographic and clinical aspects, were analyzed. Participant's mean age was 44.3 and the average marriage duration was 22.6 years. The initial HPV prevalence was 4.7%. After one year, the HPV clearance rate among initially positive women was 84.3%. The rate of new HPV infections among initially negative women after 5 years was 0.2%, resulting in a cumulative HPV prevalence of 5% over the study period. The incidence rate was estimated at 47 per 100,000 person-years. Parity was the only independent factor inversely associated with HPV positivity, with an odds ratio of 0.93 (95% confidence interval: 0.8 - 0.99). The prevalence of HPV in Saudi women was relatively low, suggesting a low transmission rate of HPV. This finding indicates the need for continuous monitoring and tailored prevention strategies.

Comparative study of topical 5-aminolevulinic acid photodynamic therapy and surgery for recurrent cervical high-grade squamous intraepithelial lesions following surgery

ObjectiveThe study aimed to compare the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and surgery in treating recurrent cervical high-grade squamous intraepithelial lesions (HSIL) after surgery due to precancerous lesions. MethodsA total of 41 patients with recurrent cervical HSIL after surgery for precancerous lesions were studied retrospectively. Patients underwent ALA-PDT or surgery and were followed up at 3, 6, 9 and 12 months and then every six months after that. Clinical data were collected and the efficacy and safety of the two treatment methods were compared. ResultsOf the 41 patients with recurrent cervical HSIL after conization, 15 cases received ALA-PDT and 26 received surgery. At the six-month follow-up, the lesions’ complete remission (CR) rate was 93.33 % in ALA-PDT group and 88.46 % in the surgery group. The human papillomavirus (HPV) clearance rates were 66.67 % and 73.08 %, respectively. No significant differences concerning the lesions’ CR rate and the HPV clearance rate were observed between the two groups (P>0.05). At the twelve-month follow-up, the HPV clearance rates were 80.00 % and 91.67 %. No significant differences concerning the HPV clearance rate were observed between the two groups (P>0.05). In the surgery group, the HPV clearance rate and the lesions’ CR rate were lower in patients over 45 years of age (25.00% vs. 81.82 %, P = 0.031; 50.00% vs. 95.45 %, P = 0.052). During the follow-up, there was no significant difference in the recurrence rate between the two groups (P>0.05). In addition, none of the patients progressed. In women treated with ALA-PDT, there was no vaginal bleeding, and no harmful effects on the cervical organizational structure or functions compared to the surgery group, and two women delivered successfully after ALA-PDT treatment. ConclusionsThe efficacy of ALA-PDT was similar to that of surgery in treating recurrent cervical HSIL following surgery, with fewer side effects.

Focused ultrasound versus the loop electrosurgical excision procedure to treat women with cervical high-grade squamous intraepithelial lesions under 40: a retrospective study

BackgroundThis study aimed to compare the efficacy of focused ultrasound (FUS) and the loop electrosurgical excision procedure (LEEP) for the treatment of cervical high-grade squamous intraepithelial lesions (HSILs) among women of reproductive age.MethodsCase records of patients aged < 40 years who were treated for cervical HSILs using either FUS or LEEP from September 1, 2020 to May 31, 2022 were retrospectively reviewed. Patients were followed up for cure, recurrence, human papillomavirus (HPV) clearance, and complications within 1 year of treatment. Odds ratios and 95% confidence intervals were determined using univariate and multivariate logistic regression models to analyze the association between disease evidence or HPV clearance and treatment modalities or other covariates.ResultsOf the 1,054 women who underwent FUS or LEEP, 225 met our selection criteria. Among the selected women, 101 and 124 received FUS and LEEP, respectively. There was no significant difference between the FUS and LEEP groups in the cure rate during the 3–6 months of follow-up (89.11% vs. 94.35%, P = 0.085) and recurrence rate during the 6–12 months follow-up (2.22% vs. 1.71%, P = 0.790). Both groups exhibited enhanced cumulative HPV clearance rates; however, the rates were not significantly different between the FUS and LEEP groups (74.23% vs. 82.79%, P = 0.122 during the 3–6 months follow-up; 84.95% vs. 89.17%, P = 0.359 during the 6–12 months follow-up). Furthermore, the incidence of complications caused by the FUS and LEEP techniques was comparable (5.0% vs. 5.6%, P = 0.818).ConclusionsWe found that FUS and LEEP have similar efficacy, safety, and reliability in treating women (aged < 40 years) with HSILs.

HPV vaccination among eligible HIV-positive adults: a best practice implementation project.

The aim of this best practice implementation project was to promote evidence-based practices (EBPs) for human papilloma virus (HPV) vaccination among eligible HIV-positive patients. HPV-induced cancers are largely preventable by prophylactic vaccination of HPV-naïve individuals. Immunosuppression in HIV-positive patients prevents clearance of HPV, which increases the risk of developing cancer. Health care agencies caring for individuals living with HIV must implement interventions to enhance uptake of HPV vaccination. This project was guided by the JBI Model of Evidence-Based Healthcare and JBI's Getting Research into Practice (GRiP) tool. A baseline audit was conducted to assess current practice against EBPs and to identify areas for improvement. A follow-up audit was used post-implementation to determine whether compliance with EBPs improved. The baseline audit revealed an average compliance rate of 46% with the two EBPs for increasing vaccination uptake. Three barriers to compliance were identified and strategies were implemented to address these barriers. The follow-up audit revealed 71% average compliance with the EBPs, a 25% increase from baseline. Interventions aimed at promoting HPV vaccination among HIV-positive individuals can reduce the risk of specific cancers. This project revealed an increase in compliance with EBPs for HPV vaccination for eligible HIV-positive patients when a vaccination reminder and recall system was placed in a frequently visited section of the electronic health record. However, a more sustainable solution would be to collaborate with the information technology staff to ensure that the health maintenance section in the electronic health record is configured correctly.

Colposcopy and Smoking Cessation: Survey and Education Intervention Pilot Study

Objective: The objective of the study was to understand variations in smoking cessation practices across Canadian colposcopy clinics and to assess improvements in smoking cessation counseing after the provision of jurisdiction-specific resources. Methods: An electronic survey was sent to members of the Society of Canadian Colposcopists and the Gynaecologic Oncologists of Canada to characterize current smoking cessation counseling practices to inform the design of the educational initiative. Colposcopy clinics were invited to participate in the pilot involving the collection of smoking counseling data from patient charts pre- and postintervention. Region-specific smoking cessation resource toolkits were created for participating clinics. Descriptive statistics were used for the analysis. Results: 32/266 colposcopists responded to the survey. 25/32 respondents indicated that they asked all patients about their smoking status. Most respondents indicated that they tell patients smoking increases the risk of developing cervix cancer (88%) and that smoking negatively affects the immune system and human papillomavirus clearance (94%). Five clinics participated in the education initiative. While there is variation in practice, after providing smoking cessation resources to clinics, both assessing smoking status and smoking cessation counseling improved with most sites increasing their referral rates to family doctors or smoking cessation clinics (range: 10%–50%). Conclusions: Gaps exist in smoking cessation counseling in some Canadian colposcopy clinics. Standardizing assessment and documentation of smoking status, using effective models of counseling, and providing jurisdiction-specific resources to colposcopy clinics may improve smoking cessation counseling.

High prevalence of high-risk HPV genotypes in individuals attending an infectious diseases clinic from 2018 to 2022 in Milan, Italy.

Human papillomavirus (HPV) is the most common sexually transmitted infection, linked to several types of lesions. HPV, specifically HPV 16, accounts for most of anal cancer cases. In this study, we evaluated the proportion of samples tested positive for HPV and characterized genotypes distribution in anal specimens collected from individuals at risk of anal HPV infection attending from 2018 to 2022 a large Infectious Diseases Department in Italy. The presence of HPV DNA was investigated through a commercial kit detecting 12 HR-HPV, 8 probable/possible HR-HPV, and 8 LR-HPV genotypes. Among 1514 samples, 84% (1266/1514) resulted positive for any type of HPV. The prevalence of high-risk HPV types remained high during all the years of the study period, from 2018 to 2022, ranging from 65% to 73%. Most of HR-HPV, LR-HPV and HPV 16 positive samples were collected from men >45 years. HPV 16 was also the most frequent type in men and women. We did not observe significant variations between years in detection of HR-HPV, instead of LR-HPV, that significantly decreased. In conclusion, the high prevalence of oncogenic HPV genotypes underlines the necessity of clear anal HPV screening guidelines and, along with frequent HR-HPV coinfections, reinforces the urge to intensify the anti-HPV vaccination campaign.

Comparative study of topical 5-aminolevulinic acid photodynamic therapy and surgery in treating vaginal high-grade squamous intraepithelial lesions following hysterectomy

ObjectiveTo compare the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and surgery in treating vaginal high-grade squamous intraepithelial lesions (HSIL) after hysterectomy due to cervical cancer (CC) or precancerous lesions. MethodsA retrospective study was performed comprising 41 women with histologically confirmed vaginal HSIL after hysterectomy for CC or cervical HSIL. Patients were treated with surgery or ALA-PDT and were followed up at 3, 6 and 12 months and then every six months afterwards. Clinical data were collected and the efficacy and safety of the two groups were analyzed. ResultsOf the 41 patients with vaginal HSIL after hysterectomy, 18 were treated with ALA-PDT and 23 underwent surgery. There was no significant difference in the lesions’ complete remission (CR) rate or the human papillomavirus (HPV) clearance rate between the ALA-PDT group and the surgery group (P > 0.05). In the surgery group, the clearance rate of HPV16/18 was higher than that of other high-risk HPV (HR-HPV) and HPV16/18 combined with other HR-HPV (87.50 % vs. 45.45 % vs. 0.00 %, P = 0.014). No significant difference in the recurrence rate between the two groups was noted (P > 0.05). And none of the patients progressed. In the surgery group, one patient developed significant thickening of the vaginal stump, and one patient had increased vaginal discharge. In women treated with ALA-PDT, there was no vaginal bleeding or harmful effects on the organizational structure or functions compared to the surgery group. ConclusionsThe efficacy of ALA-PDT was comparable to that of surgery in treating vaginal HSIL following hysterectomy due to CC or cervical HSIL, with fewer side effects.

Abstract B127: The impact of sociodemographic and lifestyle factors on the vaginal microbiome and cervical cancer disparities in Native American women

Abstract Cervical cancer morbidity and mortality are continually experienced by Native American women compared to white women. Human papillomavirus (HPV) is the most common sexually transmitted infection and can cause cervical cancer in women when HPV is not cleared by an individual. Depletion of Lactobacillus species in the vaginal microbiome (VMB) is linked to HPV acquisition and persistence of HPV infection and development/progression of cervical neoplasm. Most Lactobacillus spp. protect the host against invading pathogens of the genital mucosa, including the cervix. Changes in the VMB composition to dysbiotic anaerobes decrease an individual’s ability to clear HPV, increasing susceptibility to malignancy. Depletion of Lactobacilli is associated with race and ethnicity, despite research showing genetics to be statistically similar across ethnicities. However, there may be other factors that drive changes in the microbiome, including demographic, socio-economic, lifestyle and sexual &amp; reproductive health factors. Here, we aim to determine which demographic, socioeconomic, lifestyle and sexual &amp; reproductive health factors impact the microbial community within the VMB, regardless of race and ethnicity. These factors have not been studied in the context and inclusion of NA women. In this study, 31 women at the Native American for Community Action Clinic in Flagstaff, Arizona, U.S. were enrolled, and participants completed self-reported surveys. The survey assessed the individual’s socioeconomic, demographics, lifestyle, reproductive health, as well as their knowledge on HPV and VMB. Vaginal swabs were also collected for microbiome analysis via 16S rRNA sequencing. Surveys were collected and stored in REDCap. Surveys were statistically analyzed using t-test, Fisher’s exact, or Chi-square tests. Most women identified as NA (n=16), white (n=13), and Hispanic (n=5). We identified bacterial profiles of 28 of the 31 participants to be Lactobacillus-dominant (n=16) and non-Lactobacillus-dominant (n=12) and stratified them into two groups. Significant differences were observed, suggesting association of multiple people in a household (p=0.0228), lower level of education (p=0.0093), and high parity (p=0.0283) to undesirable non-Lactobacillus-dominant VMB. It is noteworthy that there were no differences between groups regarding race/ethnicity, age, body mass index, marital status, employment status, household income, hrHPV positivity, vaccination status, use of contraceptives, sexual activity, number of partners and knowledge of HPV and VMB. Yet, the non-Lactobacillus group tended to have more women with high-risk HPV infection. Ongoing analysis includes global health and perceived stress data in relation to the VMB and HPV status. Upon full analysis, we will report on trends between the VMB composition and sociodemographic, lifestyle factors and quality of life. The findings will improve ways for people to find solutions to decrease HPV infections and cervical cancer in Native American populations. Citation Format: Tawnjerae Joe, Paweł Łaniewski, Tristen Eddie, Skyler Bordeaux, Verity Quiroz, Haiyan Cui, Denise Roe, Donna Peace, J. Gregory Caporaso, Naomi Lee, Melissa M. Herbst-Kralovetz. The impact of sociodemographic and lifestyle factors on the vaginal microbiome and cervical cancer disparities in Native American women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B127.

Outcome and associated factors of high-risk human papillomavirus infection without cervical lesions.

To study the outcome of human papillomavirus (HPV) infection in women with cervical pathology results of non-cervical intraepithelial neoplasia (CIN) or cervical cancer and positive high-risk HPV test, as well as analyze the associated risk factors affecting the outcome of infection. To investigate the outcome of high-risk (HR)-HPV infection in the female genital tract and analyze the associated risk factors affecting their outcome, a total of 196 women with positive HR-HPV test results and non-CIN or cervical cancer cervical pathology results were selected for follow-up at the Cervical Disease Clinic of the Obstetrics and Gynecology Hospital, Zhejiang University School of Medicine from January 2017 to March 2020. The follow-up interval was every 6 months, and both cervical cytology (TCT) and HR-HPV testing were performed at each follow-up visit. If the cervical cytology results were normal upon recheck and the HR-HPV test was negative, the woman was considered to be cleared of the HPV infection and was entered into the routine cervical screening population. When the repeat HR-HPV test remained positive after 6 months, the woman was defined as having a persistent HR-HPV infection. If HR-HPV persisted but the TCT results were normal, follow-up was continued. If HR-HPV persisted and the TCT results were abnormal, a colposcopy-guided biopsy was performed immediately. In this situation, if the histological results were still non-CIN or cervical cancer, the follow-up was continued. If the histological results confirmed the development of CIN or invasive cancer, then enter another study follow-up to further track its development and outcome, and the woman commenced the treatment process. The HPV infection clearance time was analyzed by the Kaplan-Meier method, and the comparison of the HPV clearance rate and infection clearance time between each of the different groups was performed using aχ2 test or Fisher's exact test, as appropriate. After the univariate analysis, several significant factors were included in the Cox model and independent risk factors were analyzed. A total of 163 women were enrolled in this study. The median age was 40.0 years (22-67 years) and the median follow-up time was 11.5 months (6-31 months). The spontaneous clearance rate of HR-HPV infection was 51.5%, and the median time to viral clearance was 14.5 months. Age and the initial viral load were high risk factors affecting the spontaneous clearance of HR-HPV infection. The factors significantly associated with HPV clearance rate and time to HPV clearance consisted of menopause and full-term delivery (P < 0.05). In women with normal or low-grade lesions on the cell smear, the spontaneous clearance rate of HR-HPV infection was 51.5% and the time to clearance was 14.5 months. Age and the initial viral load were independent associated factors affecting the spontaneous clearance of HR-HPV infection in the female genital tract. These findings suggest that non-young women or those with high viral loads have a higher rate of persistent HR-HPV infection. Thus, intensive screening should be recommended.

Ecological diversity profiles of non-vaccine-targeted HPVs after gender-based community vaccination efforts

The long-term effect of population-level human papillomavirus (HPV) vaccination on the viral ecology of the untargeted HPVs is poorly understood. We performed an 8-year follow-up of 33 communities randomized to gender-neutral HPV16/18 vaccination, girls-only HPV16/18 vaccination, and control communities without HPV vaccination. The 1992/93 and 1994 birth cohorts were invited in school years 2007/8 and 2008/9. Follow-up cervico-vaginal sampling at 18 and 22 years of age, 4 and 8 years post-vaccination, respectively, were attended by 11,396 and 5,602 participants. HPV types 6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68 were genotyped and used for the community-level ecological diversity estimations. Gender-neutral vaccination communities with a stronger herd immunity than girls-only vaccination communities show a significantly increased HPV α-diversity (p=1.1×10-8) from 4 to 8 years post-vaccination, despite the clearance of the vaccine-targeted HPVs in these communities. This likely sign of niche occupation by the non-vaccine-targeted HPVs will potentially affect the future cervical cancer screening programs but should not interfere with the WHO mission to eliminate cervical cancer.

Prospective cohort study of 5-aminolevulinic acid photodynamic therapy for cervical low-grade squamous intraepithelial lesions with human papillomavirus infection

BackgroundSome patients with cervical low-grade squamous intraepithelial lesions (LSIL) undergo invasive laser ablation or loop electrosurgical excision procedures. Photodynamic therapy (PDT) is a photosensitizer 5-aminolevulinic acid (5-ALA)-based minimally invasive technique that causes minimal normal tissue and cell damage. We investigated 5-ALA-mediated PDT efficacy for cervical LSIL complicated by human papillomavirus (HPV). MethodsThis prospective cohort study was conducted on patients with cervical LSIL, who were divided into treatment (20 % 5-ALA PDT thrice every 7–14 days; n = 216) and control (observation; n = 220) groups. The treatment group underwent cervical cytology and HPV genotyping 3 months after treatment; both groups underwent cervical cytology, HPV genotyping, colposcopy biopsy, and histopathological examination 6 and 12 months post-treatment. ResultsThe 3-, 6-, and 12-month follow-ups revealed gradually improved cervical cytology findings: no intraepithelial lesions or malignant tumor (NILM) rates (approximately 80 %). The HPV clearance rate (baseline subtype) was approximately 68 %: approximately 60 % for HPV16/18 and 71 % for non-HPV16/18 baseline subtypes. By months 6 and 12 after PDT, the LSIL regression rate of cervical histopathology increased (75.46 %–82.08 %). The 6- and 12-month follow-ups revealed significantly increased cervical LSIL regression rates in the treatment group. Compared with the control group, the number of HPV subtypes in the treatment group decreased significantly by 6 and 12 months. Conclusions5-ALA PDT effectively eliminated cervical LSIL and HPV, with sustained effects for up to 12 months post-treatment. Therefore, 5-ALA PDT is an effective and safe treatment for cervical LSIL with HPV that promotes cervical LSIL regression to normal cervical tissue.

Incidence, clearance, and factors associated with anal human papilloma virus infection among men with HIV.

This study aims to estimate the incidence and persistence/clearance of anal human papilloma virus (HPV) infection and related factors among men with HIV in Taizhou, China. A prospective cohort study. Men with HIV were recruited and followed up from 2016 to 2021. Questionnaire surveys were used to collect social-demographic and behavioral characteristics, and anal swabs were collected for HPV Genotyping. A total of 675 men with HIV were recruited and followed up. After an average follow-up time of 1.75 years, HPV39 (3.8/100 person-years), HPV52 (3.6/100 person-years), HPV51 (3.1/100 person-years), HPV58 (2.5/100 person-years) and HPV16 (2.4 cases/100 person-years) in the high-risk types showed the highest incidence rate. In marriage with woman [adjusted hazard ratio (aHR) = 0.44, 95% confidence interval (CI) 0.20-0.99] showed an inverse association with HPV incidence, while bisexuality or undetermined sexual orientation (aHR = 2.62, 95% CI 1.08-6.36) showed a positive association. For those infected at baseline, the top three high-risk HPV with the lowest clearance density were HPV52 (32.2/100 person-years), HPV58 (38.1/100 person-years), and HPV16 (43.5/100 person-years). Daily consumption of 1-28 g alcohol (aHR = 0.62, 95% CI 0.41-0.95) showed an inverse association with HPV clearance, while illicit drug use (aHR = 3.24, 95% CI 1.59-6.59) showed a positive association. Anal HPV infection and clearance were both active in men with HIV in China. Marriage status and sexuality were associated with the incidence of HPV infection, while substance use including alcohol and illicit drug were associated with HPV clearance. More studies are needed to explore the risk factors of HPV persistence.

Efficacy of Lactococcus lactis strain Plasma on clearance of anal HPV infection in men who have sex with men: A single-center, double-blinded, randomized placebo-controlled trial (CLEAR HPV study)

Background: Anal cancer is a human papillomavirus-related cancer; specifically, it is preceded by high-grade squamous intraepithelial lesions, which are less likely to regress spontaneously than low-grade intraepithelial lesions. Although most human papillomavirus (HPV) infections are thought to clear spontaneously, anal HPV infection persists, especially in people living with HIV. Preliminary results from a recent small randomized placebo-controlled trial of oral bacteriotherapy using a high dose of probiotics demonstrated clearance of anal high-risk HPV (hr-HPV) infection and lower onset of new high-grade squamous intraepithelial lesions among people living with HIV. Lactococcus lactis strain Plasma is a lactic acid bacterium directly activating plasmacytoid dendritic cells and inducing release of type I and III interferons via Toll-like receptor 9 stimulation. Based on these findings, oral bacteriotherapy with LC-plasma may contribute to clearing anal hr-HPV infection and reducing anal precancerous lesions by activating innate and acquired immune responses. This randomized placebo-controlled trial aims to investigate the efficacy and safety of LC-plasma therapy in clearing anal hr-HPV infection and reducing anal precancerous lesions among men who have sex with men with or without HIV infection. Methods: Participants with anal hr-HPV infection will be included and receive test capsules. A total of 150 patients will be included in the intervention group with follow-up, which will consist of HPV genotype test, cytology by anal pap smear, and biopsy with high-resolution anoscopy. The primary endpoint will be the clearance rate of the hr-HPV genotype infection at the anal site at 180 days. The secondary endpoints will be changes in anal epithelial neoplasia detected using high-resolution anoscopy at 180 days; change in abnormal cytology by anal pap smear at 180 days; change in hr-HPV genotype at the anal site at 180 days; change or percentage change in peripheral blood CD4 positive T-lymphocyte numbers in HIV-infected participants at 180 days; changes in quantitative hepatitis B surface antigen levels at 180 days in the HBV-infected participants; and adherence to the study drugs. Conclusion: This randomized controlled study will provide data on the efficacy and safety of LC-plasma as a treatment for anal HPV infection and grade 2 or 3 anal intraepithelial neoplasia.