Effect of Oral Probiotics Use in HR-HPV Clearance, a Retrospective Study

BackgroundProbiotics has been shown to be effective in reducing vaginal colonization of pathogenic organisms. The aim of this study was to investigate the influence of probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on genital high-risk human papilloma virus (HR-HPV) clearance and quality of cervical smear.MethodsThis was a randomized, double-blinded, placebo-controlled trial. Women with genital HR-HPV infection were randomized into study and control groups. A probiotic or placebo preparation was administered orally (one capsule daily) until negative HR-HPV testing. A cervical smear and HR-HPV tests were performed at the beginning of the study and every 3 months thereafter until a negative result was obtained.ResultsA total of 121 women with genital HR-HPV infection were enrolled (62 in the study group and 59 in the control group). There was no significant difference in HR-HPV clearance rate between the two groups (58.1% vs. 54.2%). The only factor predicting HR-HPV clearance was a lower initial viral load (HR 3.214; 95% CI: 1.398, 7.392; p = 0.006). Twenty-two women had a mildly abnormal initial cervical smear and nine had an unsatisfactory smear. At 6 months follow-up, both mildly abnormal cervical smear and unsatisfactory smear rates had decreased significantly in the study group compared to the control group (p = 0.017 and 0.027).ConclusionsThe application of probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 did not influence genital HR-HPV clearance, but may have decreased the rates of mildly abnormal and unsatisfactory cervical smears.Trial registrationClinicaltrials.gov NCT01599416, May, 2012. Retrospectively registered.

Aim: This study aims to investigate the effects of COVID-19 (SARS-CoV-2) vaccines on high-risk Human Papillomavirus (hr-HPV) clearance and cervical cytology results in patients undergoing cervical excisional procedures. Materials and Methods: A total of 686 patients were analyzed in the Gynecological Oncology Surgery Clinic between October 2020 and July 2022. Among these, 350 patients had not received the COVID-19 vaccine, and 336 had received it. Cervical cytology and hr-HPV DNA analysis were performed on the patients 6 months after the cervical excisional procedure. Clinical data, including patients' vaccination status, were obtained from the national electronic medical record database, patient files, and face-to-face inquiries. Results: There was no significant difference between the vaccinated and unvaccinated groups in terms of age, parity, smoking, oral contraceptive use, cervical cytology, hr-HPV DNA status, cervical biopsy, endocervical curettage, type of excisional procedure, results of excisional procedure and endocervical curettage, and surgical margin status (p>0.05 for all comparisons). No significant difference was observed in the cervical cytology results 6 months post-procedure between the vaccinated and unvaccinated groups (p=0.566, 95% CI=1.130-1.549). Similarly, no significant difference was found in hr-HPV DNA clearance between the two groups 6 months post-procedure (p=0.217, 95% CI=1.412-1.750). Conclusion: The systemic effects of COVID-19 vaccines are not fully understood. Our study is among the few that investigate the impact of COVID-19 vaccines on hr-HPV DNA clearance and cervical cytology results. Current literature, similar to our findings, does not demonstrate a significant effect of COVID-19 vaccination on hr-HPV clearance and cervical cytology results. Given the strong immunogenic response elicited by COVID-19 vaccination, the potential impact of this non-specific systemic inflammatory response on hr-HPV DNA clearance warrants further investigation. This study found no difference in cervical cytology and hr-HPV DNA persistence between vaccinated and unvaccinated patients 6 months post-cervical excisional procedure. However, comprehensive studies are needed for better interpretation and acceptance of these findings.

Interferon-γ (IFN-γ): A possible prognostic marker for clearance of high-risk human papillomavirus (HPV)

We followed 353 women referred with abnormal cervical cytology in a non-intervention cohort study. In 91 pregnant women we compared high-risk human papilloma virus rates in the subsequent trimesters and postpartum in comparison to 262 non-pregnant women. High-risk human papilloma virus clearance was compared with 179 high-risk human papilloma virus positive non-pregnant women. Our main questions were: (1) do high-risk human papilloma virus rates change during pregnancy?; and (2) is there any difference between high-risk human papilloma virus clearance in pregnant and non-pregnant women? Women were monitored 3–4 monthly by cytology, colposcopy, and high-risk human papilloma virus testing. The median follow-up time was 33 months (range 3–74). Non-pregnant women showed prevalence rates of high-risk human papilloma virus of 64, 57, 53, and 50%, respectively, in four subsequent 3-months periods since the start of the study. These high-risk human papilloma virus rates were higher than in the three trimesters of pregnancy, and during the first 3 months postpartum, i.e. 50, 44, 45, and 31%, respectively. Postpartum only, this difference was statistically significant (P=0.004). Paired comparisons of high-risk human papilloma virus prevalence rates of the different trimesters with the postpartum rate showed (McNemar test) decreased rates: first trimester: 18% (P=0.02), second trimester: 13% (P=0.02) and third trimester: 23% (P<0.005). Such a phenomenon was not found in non-pregnant women. Pregnant women showed a trend for increased high-risk human papilloma virus clearance during the third trimester and postpartum compared to non-pregnant women (hazard ratios 3.3 (0.8–13.7) and 4.6 (1.6–12.8), respectively). These results suggest a lowered immune-response against human papilloma virus during the first two trimesters of pregnancy with a catch-up postpartum.British Journal of Cancer (2002) 87, 75–80. doi:10.1038/sj.bjc.6600367 www.bjcancer.com© 2002 Cancer Research UK

To estimate incidence and clearance of high-risk human papillomavirus (HR-HPV), and their risk factors, in men who have sex with men (MSM) recently infected by HIV in Spain; 2007-2013. Multicenter cohort. HR-HPV infection was determined and genotyped with linear array. Two-state Markov models and Poisson regression were used. We analysed 1570 HR-HPV measurements of 612 MSM over 13 608 person-months (p-m) of follow-up. Median (mean) number of measurements was 2 (2.6), median time interval between measurements was 1.1 years (interquartile range: 0.89-1.4). Incidence ranged from 9.0 [95% confidence interval (CI) 6.8-11.8] per 1000 p-m for HPV59 to 15.9 (11.7-21.8) per 1000 p-m for HPV51. HPV16 and HPV18 had slightly above average incidence: 11.9/1000 p-m and 12.8/1000 p-m. HPV16 showed the lowest clearance for both 'prevalent positive' (15.7/1000 p-m; 95% CI 12.0-20.5) and 'incident positive' infections (22.1/1000 p-m; 95% CI 11.8-41.1). More sexual partners increased HR-HPV incidence, although it was not statistically significant. Age had a strong effect on clearance (P-value < 0.001) due to the elevated rate in MSM under age 25; the effect of HIV-RNA viral load was more gradual, with clearance rate decreasing at higher HIV-RNA viral load (P-value 0.008). No large variation in incidence by HR-HPV type was seen. The most common incident types were HPV51, HPV52, HPV31, HPV18 and HPV16. No major variation in clearance by type was observed, with the exception of HPV16 which had the highest persistence and potentially, the strongest oncogenic capacity. Those aged below 25 or with low HIV-RNA- viral load had the highest clearance.

High-risk human papillomavirus (HR-HPV) infection is the most common sexually transmitted infection. Penile and cervical cancer rates are highest in sub-Saharan Africa. However, little is known about the impact of HIV infection on HR-HPV acquisition and clearance among heterosexual men. HR-HPV incidence and clearance were evaluated in 999 men (776 HIV-negative and 223 HIV-positive) aged 15-49 years who participated in male circumcision trials in Rakai, Uganda. Penile swabs were tested for HR-HPV by Roche HPV Linear Array. A Poisson multivariable model was used to estimate adjusted incidence rate ratios (adjIRRs) and clearance risk ratios (adjRRs). HR-HPV incidence was 66.5/100 person-years in HIV-positive men and 32.9/100 person-years among HIV-negative men [IRR=2.02, 95% confidence interval (CI) 1.67-2.44]. Incidence was higher in the unmarried men (adjIRR=1.73, 95% CI 1.19-2.52), and decreased with age (adjIRR for men >35 years=0.64, 95% CI 0.43-0.94) and male circumcision (adjIRR=0.70, 95% CI 0.55-0.89). HR-HPV clearance was 114.7/100 person-years for HIV-positive men and 170.2/100 person-years for HIV-negative men (risk ratio=0.67, 95% CI 0.59-0.77). HR-HPV clearance in HIV-negative men increased with circumcision (adjRR=1.48, 95% CI 1.26-1.74), HSV-2 infection (adjRR=1.20, 95% CI 1.01-1.44), and symptoms of urethral discharge (adjRR=1.35, 95% CI 1.06-1.73). Clearance of HR-HPV was significantly lower for unmarried men (adjRR 0.76, 95% CI 0.59-0.98). HR-HPV is common among heterosexual Ugandan men, particularly the HIV-infected. HIV infection increases HR-HPV acquisition and reduces HR-HPV clearance. Promotion of male circumcision and additional prevention measures, such as HPV vaccination, is critical in sub-Saharan Africa.

Clearance of high-risk human papillomavirus (HPV) DNA and PAP smear abnormalities in a cohort of women subjected to HPV screening in the New Independent States of the former Soviet Union (the NIS cohort study)

We assessed the relation between clearance of high-risk human papillomavirus (HR-HPV) after large loop excision of the transformation zone (LLETZ) and absence of residual disease, in women diagnosed with cervical cancer (CC) and adenocarcinoma in situ (AIS). Data were collected from 92 women diagnosed with CC and AIS who were positive to HR-HPV and had a repeat cervical HPV test 3-12 weeks after LLETZ (in which CC/AIS were diagnosed) and before final surgical treatment. We compared characteristics of women with negative and positive HR-HPV after LLETZ. The HR-HPV results after the LLETZ operation were negative in 40 women and positive in 52 women. The HR-HPV-negative group included a significantly higher incidence of AIS: 14 (35%) vs 5 (9.6%, p < .006).In the negative HR-HPV post-LLETZ group, 36 (90%) had normal histology and only 2 (5%) had cancer in the final histological specimen. Among 34 women who underwent radical hysterectomy/trachelectomy after LLETZ, a normal final histology was observed in 75% and 9% of those who were HR-HPV negative and HR-HPV positive, respectively (p < .0005). The positive predictive value for absence of residual cancer, with clearance of HR-HPV after LLETZ, was 95%. Clearance of HR-HPV from the cervix a short time after LLETZ has a high association with the absence of residual cancer in the final outcome, either in the pathology or the follow-up. Testing for HR-HPV a short time after LLETZ might serve as a parameter for risk assessment.

In The Netherlands and most other European countries, women with two serial cervical smears with borderline or mild dyskaryosis (BMD) within 6 months are referred for colposcopy-directed biopsies. Only about 10% of these women have high-grade cervical intraepithelial neoplasia (CIN). This study therefore investigated whether human papillomavirus (HPV) testing could identify which women with smears read as BMD are most likely to have high-grade CIN, either at referral or during follow-up and the relationship was determined between clearance of high-risk HPV and regression of abnormal cytology. Women with smears read as BMD (n=278) were referred to the gynaecologist for colposcopy. They were subdivided into two groups; group A comprised women with a single smear (n=172) and group B women with two sequential smears (n=106) read as BMD before referral. High-risk HPV detection with Hybrid Capture II (HC II) was performed on a cervical scrape taken at the first visit before colposcopy (i.e. baseline smear) and during follow-up. Biopsies were taken when lesions suspected for CIN were seen at colposcopy. High-risk HPV DNA was present in the baseline smears of 126 (45.0%) women; 26 (20.6%) of them had histologically confirmed CIN 2/3 at the first visit and another 14 (11.1%) during follow-up. Only one of the 152 women (0.7%) with a negative high-risk HPV test had a CIN 2 lesion at the first visit and no CIN lesions were detected during follow-up of these women. After exclusion of women who were treated for prevalent high-grade CIN, the median follow-up times were 1.3 years (range 0.0–4.3 years) and 1.6 years (range 0.0–4.5 years) for women with HPV-negative and HPV-positive baseline smears, respectively. The sensitivity of a positive high-risk HPV test for CIN 2/3 at the first visit was 96.3%, the specificity 60.2%, the positive predictive value 20.6%, and the negative predictive value 99.3%. These values did not change markedly when stratified for group A or group B. Thus, a high-risk HPV positive test was strongly associated with the presence at the first visit and the development of CIN 2/3 lesions during follow-up. Moreover, regression of abnormal cytology in women with a positive high-risk HPV test at baseline was strongly associated with viral clearance and occurred 0.3 years (range −1.2 to 1.7 years) later than HPV clearance. This study establishes the value of a high-risk HPV positive test for women at risk of high-grade CIN, with virtually no risk for missing CIN 2/3. Addition of a test on high-risk HPV in women with BMD could prevent 55% of the referrals and/or repeat smears. Copyright © 2001 John Wiley & Sons, Ltd.

In The Netherlands and most other European countries, women with two serial cervical smears with borderline or mild dyskaryosis (BMD) within 6 months are referred for colposcopy-directed biopsies. Only about 10% of these women have high-grade cervical intraepithelial neoplasia (CIN). This study therefore investigated whether human papillomavirus (HPV) testing could identify which women with smears read as BMD are most likely to have high-grade CIN, either at referral or during follow-up and the relationship was determined between clearance of high-risk HPV and regression of abnormal cytology. Women with smears read as BMD (n=278) were referred to the gynaecologist for colposcopy. They were subdivided into two groups; group A comprised women with a single smear (n=172) and group B women with two sequential smears (n=106) read as BMD before referral. High-risk HPV detection with Hybrid Capture II (HC II) was performed on a cervical scrape taken at the first visit before colposcopy (i.e. baseline smear) and during follow-up. Biopsies were taken when lesions suspected for CIN were seen at colposcopy. High-risk HPV DNA was present in the baseline smears of 126 (45.0%) women; 26 (20.6%) of them had histologically confirmed CIN 2/3 at the first visit and another 14 (11.1%) during follow-up. Only one of the 152 women (0.7%) with a negative high-risk HPV test had a CIN 2 lesion at the first visit and no CIN lesions were detected during follow-up of these women. After exclusion of women who were treated for prevalent high-grade CIN, the median follow-up times were 1.3 years (range 0.0-4.3 years) and 1.6 years (range 0.0-4.5 years) for women with HPV-negative and HPV-positive baseline smears, respectively. The sensitivity of a positive high-risk HPV test for CIN 2/3 at the first visit was 96.3%, the specificity 60.2%, the positive predictive value 20.6%, and the negative predictive value 99.3%. These values did not change markedly when stratified for group A or group B. Thus, a high-risk HPV positive test was strongly associated with the presence at the first visit and the development of CIN 2/3 lesions during follow-up. Moreover, regression of abnormal cytology in women with a positive high-risk HPV test at baseline was strongly associated with viral clearance and occurred 0.3 years (range -1.2 to 1.7 years) later than HPV clearance. This study establishes the value of a high-risk HPV positive test for women at risk of high-grade CIN, with virtually no risk for missing CIN 2/3. Addition of a test on high-risk HPV in women with BMD could prevent 55% of the referrals and/or repeat smears.

IntroductionPersistent infection with high-risk human papillomavirus (HR-HPV) is necessary for the development of precursor lesions and cervical cancer. HPV infection among women living with HIV/AIDS (WLHA) occurs more frequently, presents...

Objective The purpose of this study was to compare the efficacy of focused ultrasound (FU) and interferon drug therapy for cervical intraepithelial neoplasia 1 (CIN1) and chronic cervicitis associated with high risk human papillomavirus (HR-HPV) infection, as well as analyze the influencing factors. Methods A retrospective cohort study was performed from January 2017 to December 2019. A total of 592 patients were enrolled, of which 300 patients were treated with FU and 292 patients were treated with interferon drugs. Kaplan-Meier curves and a COX regression model were used to compare the curative effects of the two therapeutic methods using HR-HPV clearance as the main outcome. The relationship between age, HR-HPV infection type, pathological type, preoperative HR-HPV status and HR-HPV clearance were also analyzed. Results The median time for HR-HPV clearance was 6.00 months (95% CI: 5.24–6.76) in the FU group and 26.00 months (95% CI: 22.32–29.68) in the medication group. A significant difference was observed between the two groups (χ2 =198.902, p = 0.000). The HR-HPV clearance rate was 4.927 (95% CI 3.840–6.321; p = 0.000) times higher in the patients treated with FU than those treated with interferon drugs. In the FU group, no significant difference was observed in HR-HPV clearance rate between CIN1 and chronic cervicitis (χ2=0.660, p = 0.416), which was also insignificant between HR-HPV persistent and non-persistent infections (χ2=0.751, p = 0.386). Conclusion FU therapy can eliminate HR-HPV infections in a short period of time. Moreover, the treatment efficacy of FU was significantly superior to that of interferon drugs.

<h3>Introduction/Background*</h3> About 40% of CC are in women under age 40 years, for whom fertility-sparing treatment might be very important and should always be considered. More than half the patients who undergo radical surgery (trachelectomy or hysterectomy) have no remnant tumor in the final pathology specimen. HPV clearance is a test of cure after conisation, but it is not a test of cure in CC. Our objective was to assess correlation of clearance of high-risk human papillomavirus (HR-HPV) after large loop excision of the transformation zone (LLETZ) with absence of residual disease, in women diagnosed with cervical cancer (CC) and Adenocarcinoma in Situ (AIS). <h3>Methodology</h3> Data was collected from 92 women diagnosed with CC and AIS who were positive to High –Risk HPV (HR-HPV), and had a repeat cervical HPV test 3-12 weeks post-LLETZ, and before final surgical treatment. We compared characteristics of women with negative and positive HR-HPV post-LLETZ. <h3>Result(s)*</h3> The pathological results of women who were HR-HPV negative (n=40) compared to HR-HPV positive (n=52) at the post-LLETZ follow-up visit included a significantly higher incidence of AIS: 14 (35%) vs 5(9.6%) (p&lt; 0.006). In the negative HR-HPV post-LLETZ group, 36 (90%) had normal histology and only 2 (5%) had cancer in the final histological specimen. Among women who underwent radical hysterectomy/trachelectomy after LLETZ, a normal final histology was observed in 75% and 9% of those who were HR-HPV negative and HR-HPV positive, respectively (p&lt;0.0005). The negative predictive value for residual cancer, with clearance of HR-HPV after LLETZ was 95%. <h3>Conclusion*</h3> Clearance of HR-HPV from the cervix a short time after LLETZ has a high correlation with the absence of residual cancer in the final outcome, either in the pathology or the follow up. Testing for HR-HPV a short time after LLETZ might serve as a parameter for risk assessment.

This study aimed to identify factors that predict clearance of high-risk human papillomavirus (HPV) infection and progression to cervical intraepithelial neoplasia (CIN) 2 or higher, in women with normal cervical histology or CIN 1. A retrospective analysis was performed on 817 high-risk HPV-infected women with histologically verified CIN 1 or normal cervical histology. Patients were followed-up for a maximum of 24 months. Cervical HPV DNA tests were performed at every visit. At the end of followup, 648/817 (79.3%) patients were free from HPV infection and 66/817 patients (8.1%) progressed to CIN 2 or higher. Age, parity, cytology and viral load at diagnosis were significantly and inversely associated with HPV clearance. Cytology, viral load and presence of CIN 1 lesions were significantly associated with lesion progression. Cytology and high-risk HPV viral load may be useful markers for the likelihood of high-risk HPV clearance and lesion progression. Histological status, parity and marital status may also be useful factors to consider when predicting progression.

Recently, conflicting results on human papillomavirus (HPV) clearance have been reported and the data on the accumulation of incident HPV infections are still fragmentary. Thus, we completed an analysis of the age-specific incidence and clearance rates of high-risk (HR) HPV infections in 448 women participating in a multi-centre screening study in three New Independent States countries. At baseline, 239 of the 448 women were negative for HR HPV DNA, whereas 209 were HR HPV-positive and cleared HR HPV during the prospective follow-up. The cumulative incidence and clearance of HR HPV were modelled using life-table techniques. The monthly incidence rates of HR HPV were significantly age dependent (p = 0.0001), whereas monthly clearance rates remained constant across the nine age groups (p = 0.920). The incidence rates (3.04% and 2.65%) exceeded the clearance rates in the two youngest age groups only, 15-20- and 21-25-year-old women, and remained lower (0-0.84%) in all other age groups. The cumulative rate of incident HR HPV infections (1.0%) was significantly lower than the overall clearance rate (1.9%) (p = 0.001). In life-table analysis, incident HR HPV infections between the nine age groups were significantly different (p = 0.0001), while cumulative HR HPV clearance was identical in all groups (p = 0.822). The accumulation of incident HR HPV infections is significantly age-related, whereas virus clearance remains constant between 15 and 60 years of age. These distinct age-specific incidence and clearance rates explain the differences in age-specific prevalence of HR HPV infections in the study population.