Human Papillomavirus Clearance Rate 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.

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.

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.

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.

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.

5-aminolevulinic acid photodynamic therapy combined with carbon dioxide laser therapy is a safe and effective treatment for vaginal intraepithelial neoplasia.

Vaginal intraepithelial neoplasia (VaIN) is a precursor of vaginal carcinoma that is often treated with CO2 laser therapy. However, recurrence after laser therapy is common, so new approaches are needed to enhance treatment effectiveness. The aim of this study was to investigate the efficacy and safety of combining 5- aminolevulinic acid photodynamic therapy (5-ALA-PDT) with CO2 laser therapy for the treatment of VaIN. Clinical data from 40 VaIN patients who received CO2 laser therapy with or without ALA-PDT were retrospectively analyzed. Cytology, human papillomavirus (HPV) status, colposcopic images, and histopathology before and after treatment were compared, and treatment efficacy, adverse reactions, and patient prognosis were assessed. There was no significant difference in the cure rate between the CO2 laser group and the CO2 laser+5-ALA-PDT group after 12 months of follow-up. The difference in HPV clearance rate between the CO2 laser only group and the CO2 laser+5-ALA-PDT group was significant at 6 and 12 months after treatment but not at 3 months after treatment. 10% patients in the CO2 laser only group experienced adverse events, while no serious adverse events were observed in the CO2 laser+5-ALA-PDT group. 5-ALA-PDT combined with CO2 laser therapy appears to be a safe and effective treatment for VaIN that results in a high rate of HPV clearance with few side effects.

High-Intensity Focused Ultrasound for Patients With Cervical Intraepithelial Neoplasia 2/3: A Prospective One-Arm Study.

The aim of this study was to ascertain the safety of high-intensity focused ultrasound (HIFU) for high-grade cervical intraepithelial neoplasia grade 2/3 (CIN 2/3) in patients with fertility requirements. This was a prospective one-arm study. Consecutive CIN 2/3 patients diagnosed with histopathology were screened, enrolled and treated from September 2019 to September 2020 in the Affiliated Hospital of North Sichuan Medical College. All patients were treated with a combination of HIFU and antiviral treatment with REBACIN. The scheduled follow-up visits were 1 week, 1 mo, 3 mo, 6 mo and 12 mo after surgery. The primary outcomes included cure and human papillomavirus clearance rates. We screened 287 consecutive CIN 2/3 patients in our hospital, 29 of whom were enrolled and treated in this study. The cure rate reached 82.8% at 7 mo after treatment and 96.6% within 1 y. The HPV-negative rate reached 72.4% (21/29) around 6 mo after treatment, with mild side effects during and after the procedure. Our study suggests that in CIN 2/3 study participants with fertility requirements, HIFU+REBACIN therapy is a safe and effective therapeutic option with a high cure rate, HPV clearance and few side effects.

Evaluation of 5-aminolevulinic acid-mediated photodynamic therapy in postmenopausal women with persistent HPV infection with or without cervical and vaginal low-grade squamous intraepithelial lesions (CIN1/VaIN1)

ObjectiveTo analyze the efficacy and safety of photodynamic therapy (PDT) on postmenopausal women with persistent human papillomavirus (HPV) infection with or without low-grade cervical and vaginal intraepithelial neoplasia (CIN1 and VaIN1). Materials and methodsThe clinicopathological and follow-up data of 86 postmenopausal women with HPV infection (35 cases with chronic cervicitis and 51 cases with CIN1/VaIN1) were collected. All the women in this group met these criteria: menopausal time ≥ 1 year, HPV infection time ≥ 2 years, colposcopy and pathological diagnosis of biopsy ≤ CIN1/VaIN1 before PDT treatment, and 5-aminolaevulinic acid (5-ALA) as photosensitizer treating for 6 times with a week interval. The above patients were followed up 6 months and 12 months after PDT treatment, and the follow-up contents included HPV typing, cytology, colposcopy and pathological examinations. HPV negative conversion rate and lesion remission rate are the evaluation indicators of treatment efficacy. In addition, we also assessed the safety of PDT treatment. ResultsAt 12-month follow-up, the overall HPV clearance rate was 60% (45/75), of which the negative conversion rate of 16/18 HPV was 41.38% (12/29), and non-16/18 HPV was 71.74% (33/46) (p = 0.009). In patients without lesions, the HPV clearance rate was 51.72% (15/29), while in patients with CIN1/VaIN1 (n = 46), the HPV complete remission rate and lesion regression rate were 65.22% (30/46) and 89.13% (41/46), respectively. In addition, the clearance rate of HPV in lesion regression group was significantly higher than that in lesion persistence/progression group (0.00% vs. 73.17%, p = 0.003). The adverse reactions after PDT treatment were mild, mainly manifested as increased vaginal secretions or burning/tingling. ConclusionsPhotodynamic therapy can significantly enhance the elimination rate of persistent HPV infection in postmenopausal women and reduce the progression of CIN1/VaIN1. It could be an effective conservative treatment for persistent HPV infection and CIN1/VaIN1 in postmenopausal women.

Update on the Epidemiological Features and Clinical Implications of Human Papillomavirus Infection (HPV) and Human Immunodeficiency Virus (HIV) Coinfection.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) worldwide. Although most HPV infections will spontaneously resolve, a considerable proportion of them will persist, increasing the risk of anogenital dysplasia, especially within certain populations, such as patients infected with human immunodeficiency virus (HIV). Furthermore, high-risk oncogenic HPV types (HR-HPV) are the main cause of cervix and other anogenital cancers, such as cancer of the vagina, vulva, penis, or anus. HIV and HPV coinfection is common among people living with HIV (PLWH) but disproportionally affects men who have sex with men (MSM) for whom the rate of persistent HPV infection and reinfection is noteworthy. The molecular interactions between HIV and HPV, as well as the interplay between both viruses and the immune system, are increasingly being understood. The immune dysfunction induced by HIV infection impairs the rate of HPV clearance and increases its oncogenic risk. Despite the availability of effective antiretroviral therapy (ART), the incidence of several HPV-related cancers is higher in PLWH, and the burden of persistent HPV-related disease has become a significant concern in an aging HIV population. Several public health strategies have been developed to reduce the transmission of HIV and HPV and mitigate the consequences of this type of coinfection. Universal HPV vaccination is the most effective preventive tool to reduce the incidence of HPV disease. In addition, screening programs for HPV-related cervical and vulvovaginal diseases in women are well-recognized strategies to prevent cervical cancer. Similarly, anal dysplasia screening programs are being implemented worldwide for the prevention of anal cancer among PLWH. Herein, the main epidemiological features and clinical implications of HIV and HPV coinfection are reviewed, focusing mainly on the relationship between HIV immune status and HPV-related diseases and the current strategies used to reduce the burden of HPV-related disease.

Efficacy and safety of photodynamic therapy mediatied by 5-aminolevulinic acid for the treatment of vaginal high-grade intraepithelial lesions

BackgroundVaginal high-grade squamous intraepithelial lesion (HSIL) (vaginal intraepithelial neoplasia [VAIN] grade 2–3) is clinically, a precancerous lesion condition with an estimated progression rate of 10%–20%. Therefore, treatment is recommended. Because traditional treatments have limited effects, high expense and complications, here we evaluated the efficacy and safety of topical 5-aminolevulinic acid (ALA)–based photodynamic therapy (PDT). MethodsThis study consisted of 56 female patients diagnosed with vaginal HSIL. A 20% 5-ALA jelly formation was topically applied to the vaginal wall, followed by 635 nm PDT at 7–14 days intervals. Cytology, human papillomavirus (HPV) genotyping, colposcopy, and pathology were assessed after treatment. ResultsAmong the 56 patients in our study, 47 (83.9%) had VAIN 2 and 9 (16.1%) had VAIN 3. 35 patients underwent three courses of PDT treatment, 19 experienced six courses, and two experienced nine courses. The total pathological regression rate was 87.5%, and the HPV clearance rate during the 6-month follow-up was 41.9%. Lesions located in the vaginal stump after hysterectomy seem to be difficult to treat. 9%(4/44) and 23%(7/30) patients had recurrent disease during the 6-month and 1-year follow-up time point. The most common adverse event was increased vaginal discharge, other side effects include abdominal pain, vulvar pruritus, and vaginal bleeding. No severe adverse effect was observed during the treatment. ConclusionPhotodynamic therapy mediatied by 5-aminolevulinic acid is an effective and safe treatment for vaginal HSIL with minimal side effects.

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.

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.

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.

4553 An investigation into the use of curcumin, a topical herbal agent, for the treatment of cervical intraepithelial neoplasia

4553 An investigation into the use of curcumin, a topical herbal agent, for the treatment of cervical intraepithelial neoplasia

Impact of antiviral AV2 in the topical treatment of HPV-associated lesions of the cervix: Results of a phase III randomized placebo-controlled trial

BackgroundNon-surgical topical therapies have been assessed in the treatment of precancerous lesions of the cervix. Their use can offer logistical and feasibility advantages in low-resource settings. Antiviral AV2® is a mixture of natural essential oils (eugenol, carvone, nerolidol, geraniol) in olive oil, and has a broad spectrum anti-viral activity. In a phase II randomized controlled trial (RCT), AV2® proved effective in reducing the size of cervical lesions associated with human papillomavirus (HPV). The purpose of the present study was to further evaluate the efficacy of AV2 over placebo in the topical treatment of HPV-associated cervical lesions. MethodsWomen aged 25 years and older were included in this phase 3 RCT. Cytology screening, HPV testing and visual inspection of the cervix with 5% acetic acid (VIA) were performed on all participants. VIA-positive women were randomized to one of two groups to receive treatment by either AV2® or placebo. The treatment consisted of 2 puffs of spray of the investigational drug directed to the cervix. Participants were subjected to repeat examinations two months and six months later for assessment of outcomes. The primary outcome was the change of lesions on VIA at 2 months after application of the investigational drug. Secondary outcomes were: HPV clearance and cytologic regression at 2 months and 6 months, and number of participants with AEs. ResultsA total 327 VIA positive women were randomized in two groups (168 in AV2 group and 159 in placebo group). Women in the 2 groups were similar with respect to baseline demographics and clinical characteristics. At 2 months, regression of lesions on VIA was observed in 127 (89.4%) out of 142 women in AV2 group compared to 120 (91.6%) out of 131 women in placebo group (P = 0.7). On cytology, regression of lesions occurred in 14 (56%) out of 25 women in the AV2 arm and in 13 (48.1) out of 27 women in the placebo arm (p = 0.7), and HPV clearance rates were 34.1% and 35% in AV2 group and placebo group respectively (p = 0.8). At 6 months cytologic regression was observed in 64.7% of women in AV2 group and 45.8% in placebo group (p = 0.2), while HPV clearance occurred in 11 (51.9%) out of 17 women in AV2 arm versus 11 (34.4%) in placebo arm (p = 0.3).Some local side effects (burning, itching, irritation) were similarly noted in the 2 groups (p-values = 0.169, 0.623 and 0.172 respectively) but they were mild and transitory. ConclusionA topical application of AV2 onto the cervix can induce the regression of cervical precancerous lesions, but its efficacy does not significantly differ with that of placebo. The discrepancy between the expected and the recorded sample size as well as the huge number of lost to follow-up probably impeded the power of analyses, which could be one of the reasons for the lack of difference seen between AV2 and placebo. Further evaluation of the effects of AV2 with different diagnostic methods and treatment regimen and arms is warranted. Clinical trial registrationNCT02346227 registered on November 8, 2014;

Efficacy and safety of combined high-dose interferon and red light therapy for the treatment of human papillomavirus and associated vaginitis and cervicitis: A prospective and randomized clinical study.

Background:We evaluated the efficacy and safety of combined high-dose interferon (IFN) and red light therapy for the treatment of subclinical and latent human papillomavirus (HPV) infections.Methods:Ninety women diagnosed with subclinical or latent HPV infection were randomized to receive topical application of low-dose recombinant IFNα-2b (1 million IU), high-dose IFNα-2b (9 million IU), or a combination of high-dose IFNα-2b and red light therapy on the cervix and vagina. All patients received treatment once daily for 4 weeks. HPV titer was measured immediately and 4, 8, and 12 weeks after treatment to determine the rates of viral clearance and infection cure. Treatment of HPV-associated vaginitis and cervicitis was also evaluated.Results:Results showed that immediately and 4, 8, and 12 weeks after treatment, the HPV clearance rates and infection cure rates were higher in the high-dose IFN and combination groups compared to the low-dose IFN group. High-dose IFN and combination therapies were significantly effective against both low-risk and high-risk HPV infections. Although the cure rates for vaginitis and cervicitis were significantly higher in the high- compared to the low-dose IFN group, rates were even higher in the combination group compared to the high-dose IFN group. Mild adverse effects were reported by a very small subset of patients (3/30) in the combination group.Conclusions:This study suggests that combination of high-dose IFN and red light therapy is safe and effective against subclinical and latent HPV infections.

Evidence of synergistic relationships between HIV and Human Papillomavirus (HPV): systematic reviews and meta-analyses of longitudinal studies of HPV acquisition and clearance by HIV status, and of HIV acquisition by HPV status.

IntroductionObservational studies suggest HIV and human papillomavirus (HPV) infections may have multiple interactions. We reviewed the strength of the evidence for the influence of HIV on HPV acquisition and clearance, and the influence of HPV on HIV acquisition.MethodsWe performed meta‐analytic systematic reviews of longitudinal studies of HPV incidence and clearance rate by HIV status (review 1) and of HIV incidence by HPV status (review 2). We pooled relative risk (RR) estimates across studies using random‐effect models. I 2 statistics and subgroup analyses were used to quantify heterogeneity across estimates and explore the influence of participant and study characteristics including study quality. Publication bias was examined quantitatively with funnel plots and subgroup analysis, as well as qualitatively.Results and DiscussionIn review 1, 37 publications (25 independent studies) were included in the meta‐analysis. HPV incidence (pooled RR = 1.55, 95% CI: 1.29 to 1.88; heterosexual males: pooled RR = 1.95, 95% CI: 1.62, 2.34; females: pooled RR = 1.63, 95% CI: 1.26 to 2.11; men who have sex with men: pooled RR = 1.36, 95% CI: 1.01 to 1.82) and high‐risk HPV incidence (pooled RR = 2.20, 95% CI: 1.90 to 2.54) was approximately doubled among people living with HIV (PLHIV) whereas HPV clearance rate (pooled RR = 0.53, 95% CI: 0.42 to 0.67) was approximately halved. In review 2, 14 publications (11 independent studies) were included in the meta‐analysis. HIV incidence was almost doubled (pooled RR = 1.91, 95% CI 1.38 to 2.65) in the presence of prevalent HPV infection. There was more evidence of publication bias in review 2, and somewhat greater risk of confounding in studies included in review 1. There was some evidence that adjustment for key confounders strengthened the associations for review 2. Misclassification bias by HIV/HPV exposure status could also have biased estimates toward the null.ConclusionsThese results provide evidence for synergistic HIV and HPV interactions of clinical and public health relevance. HPV vaccination may directly benefit PLHIV, and help control both HPV and HIV at the population level in high prevalence settings. Our estimates of association are useful for mathematical modelling. Although observational studies can never perfectly control for residual confounding, the evidence presented here lends further support for the presence of biological interactions between HIV and HPV that have a strong plausibility.