Low-grade Cervical Lesions Research Articles

Effect of a multi-ingredient coriolus-versicolor-based vaginal gel in women with HPV-dependent cervical lesions: the PAPILOBS real-life prospective study

Human papillomavirus (HPV) is responsible for virtually all cervical cancers in women. HPV infection and persistency may lead to different-grade squamous intraepithelial lesions that can result in high-grade lesions and cancer. The objective was to prospectively evaluate the results of using a Coriolus-versicolor-based vaginal gel (Papilocare®) on HPV-dependent low-grade cervical lesion repair in a real-life scenario. HPV-positive women _ 25 years with ASCUS/LSIL cervical cytology results and concordant colposcopy images were included, receiving the vaginal gel one cannula/day for 21 days (first month) + one cannula/alternate days (five months). A 6-month second treatment cycle was prescribed when needed. Repair of the cervical low-grade lesions through cytology and colposcopy, HPV clearance, and level of satisfaction, and tolerability were evaluated. In total, 192 and 201 patients accounted for the total and safety analyses, respectively, and 77.1% repaired cervical lesions at 6 or 12 months (76.0% for high-risk HPV). Additionally, 71.6% achieved HPV clearance throughout the study’s duration (70.6% for high-risk HPV). Satisfaction level was rated 7.9 and 7.5 out of 10 at 6 and 12 months, respectively. Only three mild–moderate product-related adverse events were reported, and all of them were resolved by the end of the study. In our study, we observed higher regression rates of low-grade cervical lesions in women treated with Papilocare® vaginal gel than spontaneous regression rates reported in the literature.

Comparative analysis of Paiteling a traditional Chinese medicine (TCM) and CO2 laser therapy for high-risk HPV-associated with LSIL (CIN1) lesions

ObjectivesThis study aims to evaluate the therapeutic outcomes of Paiteling and CO2 laser therapy on high-risk human papillomavirus. MethodsWe retrospectively analyzed the data of 558 patients with HR-HPV low-grade squamous intraepithelial neoplasia (CIN1) from 2021 to 2023. Patients were selected and put into two groups: Paiteling and CO2 laser. Out of the 558 patients who were included in our final study, 239 (42.8 %) were treated with Paiteling, and 319 (57.2 %) were treated with CO2 laser vaporization. The mean age was 49.55 ± 12.10 years old. We observed that 27 (4.83 %) were younger than 30 years and 531 (95.1 %) were older than 30 years. We reviewed the patient’s results at intervals of 3 months, 6 months, 12 months, and 24 months after each therapy. The results of the recurrence rate, effective viral clearance rate, and the effectiveness of both therapies on low-grade cervical lesions were determined using multivariate and univariate cox-regression analysis. The Kaplan-Meier curve was used to determine the HR-HPV conversion rate of each therapy. ResultsThe median time for HR-HPV clearance was 6.00 months (95 % CI: 4.26–6.89) in the Paiteling group and 9.00 months (95 % CI: 15.92–22.67) in the CO2 laser group. There was a significant difference between the two groups (χ2 = 25.118, p-Value = 0.000). The HR-HPV clearance rate during 6–12 months for Paiteling and CO2 laser was 100 (55.6 %) and 80 (44.4 %), respectively. The clearance rate for both therapies from 6 to 18 months was statistically significant (6–12 months: p < 0.010, 12–18 months: p < 0.011). The Paiteling HR-HPV negative rate over 24 months 214 (89.5 %) is higher than CO2 laser 176 (55.2 %). Paiteling has a 5.4 % re-infection rate, which is marginally lower than the 5.6 % rate for CO2 lasers.The clearance rate for both therapies from 12 to 18 months [Paiteling: 20 (4.7 %) to 10 (3.6 %) and CO2 laser: 22 (8.4 %) to 15 (4.2 %)] was also significant (p < 0.011). The percentage of persistent Hr-HPV clearance rate for Paiteling patients was higher than carbon dioxide laser vaporization. No severe side effects were reported by the Paiteling patients compared to laser vaporization. This is due to the fact that Paiteling, as a traditional Chinese medicine, is a topical, non-invasive medicine, thus preserving the integrity of the cervix. ConclusionsPaiteling is an effective noninvasive therapy that can clear persistent HR-HPV associated with cervical low-grade squamous lesions in a relatively shorter period of time compared to CO2 laser ablation.

The Impact of Tamoxifen Usage in Breast Cancer Patients on the Development of Histopathological Lesions in the Cervix Uteri.

Background and Objectives: The purpose of the present study was to compare the results of colposcopic biopsies in patients with breast cancer and those who tested positive for HPV in cervix uteri cytological screenings, with a control group of HPV-positive individuals without breast cancer. Additionally, through this study, we aimed to investigate the impact of tamoxifen treatment, an anti-oestrogen drug used following breast cancer treatment, on histopathological changes. Breast cancer is the most common type of cancer and cause of death in women worldwide. Cervical cancer ranks as the second most prevalent form of cancer among women globally, with prevalence rates ranking just behind those of breast cancer. Human papillomavirus (HPV) positivity is a requirement for the development of cervical cancer, although it is not the sole factor responsible. Materials and Methods: A comparison was made between the histopathological results of 52 patients diagnosed with breast cancer, who tested positive for HPV in routine cervical cytological screenings and underwent colposcopic biopsy, and 230 cases without any abnormalities. A study was conducted to compare healthy individuals between the ages of 30 and 65 who were diagnosed with breast cancer and those who did not have breast cancer. The participants underwent HPV screening as part of the national cervical cytology screening programme. Results: The average age of those diagnosed with breast cancer was 46.73 ± 7.54; in comparison, the average age of participants in the control group was 47.49 ± 7.95. There was no statistically significant difference in age between the two groups (p: 0.530). A total of 51 cases (98.1%) of breast cancer were found to have actively used the anti-oestrogen drug tamoxifen for a duration ranging from at least 6 months to 5 years. One patient (1.9%) in the breast cancer group did not use tamoxifen. During routine cervical cytological screenings, it was observed that both breast cancer cases and healthy cases tested positive for HPV. The most commonly detected types of HPV in both groups were HPV 16 and 18, with rates of 73.1% noted in the breast cancer group and 92.6% noted in the healthy group, results consistent with the rates found in the general population. HPV 16 was found in 58.7% of participants in the control group and 42.3% of participants in the breast cancer group. There was a statistically significant difference between the two groups (p: 0.032). There was no statistically significant difference observed between the two groups in terms of normal, high-grade cervical intraepithelial lesions (HGSILs); low-grade cervical intraepithelial lesions (LGSILs); and chronic cervicitis histopathological lesions based on colposcopic and endocervical biopsy results, smear cytology, and HPV results (p-values of 0.913 and 0.877, respectively). Conclusions: Our study results indicate that tamoxifen treatment, an anti-oestrogen drug administered for chemoprevention purposes in the management of breast cancer, does not lead to an increase in abnormal histological changes in the cervix uteri. In all cases of breast cancer, gynaecological examination and cervical cytological screening should be advised.

Effects of 5-aminolevulinic acid photodynamic therapy for cervical low-grade squamous intraepithelial lesions with HR-HPV infections.

To determine the effectiveness and safety of 5-aminolevulinic acid mediated photodynamic therapy (5-ALA PDT) in HR-HPV infected patients with cervical low-grade squamous intraepithelial lesions (LSIL) and to explore possible factors affecting treatment outcomes. This retrospective study included 96 patients with histologically confirmed cervical LSIL and high-risk human papillomavirus (HR-HPV) infection. They received 5-ALA PDT treatment once a week for a total of 3 courses. All patients were evaluated by cytology tests, HPV DNA assay, colposcopy, and biopsy at 2 weeks, 3 months, and 6 months checkpoint. The chi-square test were used to evaluate the differences in various clinical data, and a p value <0.05 was considered statistically significant. At 2 weeks, 3 months, and 6 months checkpoint, colposcopies showed that the cervical iodine-unstained area under VILI (visual inspection with Lugol's iodine) significantly reduced (p < 0.01) with no structure changes. At 3 months and 6 months checkpoint, the pathological regression rate reached 87.5% (84/96) and 94.79% (91/96), while the HR-HPV clearance rates reached 80.21% (77/96) and 93.75% (90/96) respectively. We also examined the efficacy in the HPV 16/18-related group and non-HPV 16/18-related group. The HR-HPV clearance rate in the HPV16/18 group [94.87% (37/39)] was significantly higher than that of the non-HPV 16/18 group [70.17% (40/57)]. However, at 6 months after treatment, the clearance rate of the HPV 16/18 group [94.87% (37/39)] showed no statistical difference from the non-HPV 16/18 group [92.30% (53/57)]. Topical 5-ALA PDT can effectively eliminate HR-HPV infection and treat low-grade cervical squamous intraepithelial lesions, it offers an alternative treatment option for patients with LSIL, especially for those with fertility requirements and who wish to preserve cervical structure or function.

Cross-population evaluation of cervical cancer risk prediction algorithms

BackgroundCervical cancer is a preventable disease, despite being one of the most common types of female cancers worldwide. Integrating existing programs for cervical cancer screening with personalized risk prediction algorithms can improve population-level cancer prevention by enabling more targeted screening and contrive preventive healthcare innovations. While algorithms developed for cervical cancer risk prediction have shown promising performance in internal validation on more homogeneous populations, their ability to generalize to external populations remains to be assessed. MethodsTo address this gap, we perform a cross-population comparative study of personalized prediction algorithms for more personalized cervical cancer screening. Using data from the Norwegian and Estonian populations, the algorithms are validated on internal and external datasets to study their potential biases and limitations when applied to different populations. We evaluate the algorithms in predicting progression from low-grade precancerous cervical lesions, simulating a clinically relevant application of more personalized risk stratification. ResultsAs expected, our numerical experiments show that algorithm performance varies depending on the population. However, some algorithms show strong generalization capacity across different data sources. Using Kaplan-Meier estimates, we demonstrate the strengths and limitations of the algorithms in detecting cancer progression over time by comparing to the trends observed from data. We assess their overall discrimination performance in personalized risk predictions by analyzing the accuracy and confidence in individual risk estimates. Discussion and ConclusionThis study examines the effectiveness of personalized prediction algorithms across different populations. Our results demonstrate the potential for generalizing risk prediction algorithms to external populations. These findings highlight the importance of considering population diversity when developing risk prediction algorithms.

Effect of a Multi-Ingredient Coriolus-versicolor-Based Vaginal Gel in Women with HPV-Dependent Cervical Lesions: The Papilobs Real-Life Prospective Study.

Human papillomavirus (HPV) is responsible for virtually all cervical cancers in women. HPV infection and persistency may lead to different-grade squamous intraepithelial lesions that can result in high-grade lesions and cancer. The objective was to prospectively evaluate the results of using a Coriolus-versicolor-based vaginal gel (Papilocare®) on HPV-dependent low-grade cervical lesion repair in a real-life scenario. HPV-positive women ≥ 25 years with ASCUS/LSIL cervical cytology results and concordant colposcopy images were included, receiving the vaginal gel one cannula/day for 21 days (first month) + one cannula/alternate days (five months). A 6-month second treatment cycle was prescribed when needed. Repair of the cervical low-grade lesions through cytology and colposcopy, HPV clearance, and level of satisfaction, and tolerability were evaluated. In total, 192 and 201 patients accounted for the total and safety analyses, respectively, and 77.1% repaired cervical lesions at 6 or 12 months (76.0% for high-risk HPV). Additionally, 71.6% achieved HPV clearance throughout the study's duration (70.6% for high-risk HPV). Satisfaction level was rated 7.9 and 7.5 out of 10 at 6 and 12 months, respectively. Only three mild-moderate product-related adverse events were reported, and all of them were resolved by the end of the study. In our study, we observed higher regression rates of low-grade cervical lesions in women treated with Papilocare® vaginal gel than spontaneous regression rates reported in the literature.

Changes in cervical cytokine profiles following focused ultrasound treatment for high-risk human papillomavirus infection-related low-grade cervical lesions.

To evaluate the changes of cervical soluble immune markers after focused ultrasound (FU) treatment to explore the underlying local immune effects of FU in the treatment of high-risk human papillomavirus (HR-HPV) infection-related low-grade squamous intraepithelial lesion (LSIL). A total of 35 patients diagnosed with HR-HPV infection-related histological LSIL who met the inclusion criteria were enrolled in this prospective study and treated with FU. The authors used cytometric bead array to measure T-helper type 1 (Th1) cytokine (interleukin [IL] 2, tumor necrosis factor, and interferon γ) and Th2 cytokine (IL-4, IL-5, IL-6, and IL-10) levels in the cervicovaginal lavage of patients before and 3 months after FU treatment. After FU treatment, the concentrations of Th2 cytokines IL-5 and IL-6 were significantly lower than those before FU treatment (P = 0.044 and P = 0.028, respectively). HR-HPV infection was cleared in 27 patients, with a clearance rate of 77.1% (27 of 35). The concentration of IL-4 in patients with HR-HPV clearance after FU treatment was significantly lower than that in patients without HR-HPV clearance (P = 0.045). FU can inhibit the production of certain Th2 cytokines and may improve the local immune status of the cervix, thereby eliminating HR-HPV infection.

Low-Grade Cervical Intraepithelial Neoplasia (CIN1) Evolution: Analysis of Opportunistic Preventive Vaccination Role.

Low-grade cervical lesions have a high percentage of clearance in young women, even if 71-82% of low-grade intraepithelial lesion/atypical squamous cells of undetermined significance (LSIL/ASCUS) reported a High-Risk Human Papillomavirus (HR-HPV) infection, which correlates with an increased risk of Cervical Intraepithelial Neoplasia (CIN)2+. The immunogenic effect of the anti-HPV vaccine appears to be significant. The aim of the study is to evaluate the effect, two years after the diagnosis, of the anti-HPV preventive vaccination on patients with low-grade cervical lesions. We collected clinical, colposcopic, histological, and virological data from patients aged 21-45 years who attended the colposcopy service of the department of Obsetrics and Gynecology of IRCCS Foundation Policlinico San Matteo, Pavia, Italy. In the 2005-2019 period and had a low-grade pap-smear. We enrolled 422 women consecutively, divided into two groups (vaccinated and not vaccinated) for the retrospective analysis. The rate of persistence and progression of CIN were higher in the not-vaccinated group (p = 0.019). The relative risk (RR) to develop CIN2+ during follow-up vs. the the CIN1 persistence was 1.005 (95% Confidence Interval-CI 0.961-1.051) vs. 0.994 (95% CI 0.994-1.018) for age, 3.472 (95% CI 1.066-11.320) vs. 1.266 (95% CI 0.774-2.068) for non-vaccinated, 0.299 (95% CI 0.088-1.018) vs. 0.518 (95% CI 0.242-1.109) for HIV status negative, respectively. Analyzing the time to negativity, the odds ratio (OR) was 1.012 (95% CI 1-1.024) for age and 1.591 (95% CI 1.223-2.069) for vaccination; on the other hand, considering the relationship between the time to negative and the HPV genotypes contained in the 9-valent HPV vaccines, the OR was 1.299 (95% CI 1.026-1.646) for at least one of these at recruitment and 0.631 (95% CI 0.471-0.846) at follow-up. Furthermore, the presence of at least one of the HPV genotypes targeted by the HPV nonavalent vaccine is a key indicator of the risk of progression to CIN2+: OR was 3.443 (95% CI 1.065-11.189) for the presence of at least one HPV genotype at enrollment and 5.011 (95% CI 1.899-13.224) for the presence of at least one HPV genotype at follow-up, respectively. We reported in a retrospective study the benefit of anti-HPV vaccination in promoting negativity and increasing low-grade cervical lesions regression.

Evaluation of Human Papilloma Virus (HPV) Genotyping and Viral Load Determination as Diagnostic Biomarkers of Cervical Cancer Risk.

HPV testing in cervical cancer screening programs offers the possibility of introducing molecular standardized biomarkers for the triage of HPV-positive women. This study aimed to evaluate the role of HPV genotyping and viral load as possible diagnostic biomarkers of high-grade cervical lesions (CIN2+) by performing a preliminary evaluation of a new HPV test. Cervical specimens were obtained from 200 women referred for a colposcopy. Samples were tested using both Anyplex™ II HR-HPV as well as OncoPredict HPV® Screening (SCR) and quantitative typing (QT). Using a cycle threshold cutoff (Ct) of 36.8 for the SCR assay and 1.27 log10 (viral copies/104 cells) for the QT assay, relative clinical sensitivity for CIN2+ and relative clinical specificity for CIN2- as compared to Anyplex™ II HR-HPV were, respectively, 0.92 and 1.00 for SCR and 1.35 and 1.24 for QT. The distribution of high-risk HPV (HR-HPV) genotypes (p = 0.009) as well as the viral copy numbers (CIN2-: 3.7 log10 (viral copies/104 human cells); CIN2+: 4.3 log10 (viral copies/104 human cells); p = 0.047) were found to differ in women with high- and low-grade cervical lesions, suggesting a possible role of HPV genotyping and normalized viral load as potential biomarkers to identify women at increased risk of cervical lesions.

Changes in vaginal microbiome after focused ultrasound treatment of high-risk human papillomavirus infection-related low-grade cervical lesions

BackgroundIn this study, the changes of vaginal microbiome after focused ultrasound (FU) treatment were evaluated to explore the possible mechanism of FU in the treatment of high-risk human papillomavirus (HR-HPV) infection.MethodsThis study was nested in the FU arm of a prospective cohort study. A total of 37 patients diagnosed with HR-HPV infection-related cervical low-grade squamous intraepithelial lesion (LSIL) who met the inclusion criteria were enrolled in this study from October 2020 to November 2021, and these patients were treated with FU. We used 16S ribosomal RNA (16S rRNA) gene amplicon sequencing to profile the vaginal microbiota composition of patients before and 3 months after FU treatment.ResultsAfter FU treatment, HR-HPV was cleared in 24 patients, with a clearance rate of 75.0% (24/32). Lactobacillus iners was the predominant species among all samples. No significant difference was found in alpha-diversity index before and 3 months after FU treatment (P > 0.05), but the rarefaction curves showed that the vaginal microbial diversity before FU treatment was higher than that after FU treatment. Linear discriminant analysis (LDA) effect size (LEfSe) showed that Bifidobacterium contributed the most to the difference between the two groups at the genus level, and the abundance after FU treatment was significantly higher than that before treatment (P = 0.000).ConclusionsThe decrease of vaginal microbial diversity may be related to the clearance of HR-HPV infection, and FU treatment contributed to the decrease of vaginal microbial diversity. Increased Bifidobacterium abundance in the vaginal microbiome may be associated with clearance of HR-HPV infection, and FU treatment may contribute to the increase in Bifidobacterium abundance.Trial registration number: This study was registered in the Chinese Clinical Trial Registry on 23/11/2020 (ChiCTR2000040162).

Is cervical dysplasia a major concern in females with inflammatory bowel disease? A Spanish retrospective study.

Cervical cancer (CC) is the fourth most common cancer affecting women worldwide. The risk of women immunosuppressed due to AIDS or organ transplantation is well documented, as most cases are caused by persistent human papillomavirus (HPV) infection and immunosuppression can prevent clearing HPV. Although European guidelines advise that inflammatory bowel disease (IBD) women under immunosuppression should be screened for CC as regularly as high-risk patients, quality evidence is lacking in our country. We performed a retrospective case-control (2020-2021) study to analyse the risk factors associated with the appearance of low-grade (LSIL) or high-grade (HSIL) squamous intraepithelial cervical lesions in patients with IBD. We included all women aged 21-65 years , followed up at the University Hospital Fundación Alcorcón (Spain). Cases were defined as those patients with abnormalities in cervical cytology, while the control group consisted of the rest of the women. Disease characteristics, treatments and epidemiological data (smoking habit, sexual behaviour and reproductive history) were obtained. We documented the evolution of abnormalities over time and compare data between women under immunosuppressive treatment or not.

Evaluation of Sirtuin1 Overexpression by Immunohistochemistry in Cervical Intraepithelial Lesions and Invasive Squamous Cell Carcinoma.

Cervical cancer is one of the most common genital cancers in the woman with approximately half a million new cases per year. Development of invasive squamous cell carcinoma (SCC) is the result of persistent and frequent human papilloma virus infection in premalignant lesions of cervix. Thereby identification of biomarkers that could predict progression of dysplastic mucosa to invasive cancer is of great clinical significance. Overexpression of SIRT1 has been reported to induce tumorogenesis in several organs. We evaluated SIRT1 expression in normal squamous epithelium of cervix, low-grade and high-grade cervical intraepithelial lesions and invasive SCC. A total of 104 cases were selected including 34 low-grade cervical intraepithelial lesions (CINs), 37 high-grade CINs, and 35 cases of invasive SCC. The normal cervical epithelium showed negative or weak SIRT1 positivity only in basal layers. SIRT1 cytoplasmic expression was found in 13 of 34 (38.2%) of low-grade CINs, 31 of 37 (83.8%) of high-grade CINs and all 35 (100%) cases of invasive SCC. Expression between 2 groups of CIN was statistically significant ( P =0.001). Thus, SIRT1 appears to be a promising biomarker for predicting the progression of CIN to invasive SCC.

HPV-genotyping versus conventional cervical cytology as a screening method to detect dysplastic cervical epithelial changes

The world health organization (WHO) called for coordinated global action in 2018 to eliminate cervical cancer, ensuring that every woman is screened and treated for precancerous lesions (World Health Organization. Cervical cancer: an NCD we can overcome. Geneva, 2018. http://www.who.int/director-general/speeches/detail/cervical-cancer-an-ncd-we-can-overcome.tegy). Cytology-based screening has been for decades the conventional method of screening. Ancillary techniques have been added like immunocytochemistry with P16/Ki67 and L1-Capsid, but these methods require maintenance of complex infrastructure and highly trained personnel as well as relatively short screening intervals. HPV-based screening method to detect high-risk groups is a faster and automated method, which does not need morphologically highly qualified personal with high social costs. In the study, we have focused on the distribution of cervical lesions in the age groups with concordance of detection HPV high-risk subtypes (HPV-HR) and on the safety of the screening method. In the Institute for Pathology and Cytology-Schuettorf-Leer-Germany 146.800 samples of women from the age of and above 35 years were analyzed between the beginnings of 2020 until the beginning of 2021. 63.710 cases under 35 years old were analyzed. The samples were processed for both conventional cytological techniques and for molecular detection and subtyping of HPV-HR according to the advice and measurements of BD-manufacture. In this study, we have studied the histopathological results (Table 2) after colposcopy according to the age subgroups. The histopathological results were subdivided into no dysplasia, cervical intraepithelial neoplasia I (CIN I), cervical intraepithelial neoplasia II (CIN II), cervical intraepithelial neoplasia III (CIN III), squamous cell carcinoma (Sq.c.c), adenocarcinoma in situ (AIS), endometrial carcinoma, endocervical adenocarcinoma and cases without biopsy during the colposcopy (COB). We have used the muenchener classification III (Table 3) as a subgrading system for the cytological specimens. The frequency of detecting HPV56/59/66 is higher as detecting HPV-16 and HPV18 in age groups under 35 years old, 41–50 years old and 51–60 years old. HPV16 is detected higher in age groups 35–40 years old and above 60 years. The incidence of high squamous intraepithelial lesions (CIN II and III) is 0.92% in age group 35–40 years, 0.54% in age under 35 years, 0.59% in age group 41–50 years old, 0.35% in age group 51–60 years old and 0.15% in age group above 60 years old. There is no significance (p value = 0.4060). Low grade cervical lesions (CIN I) were 0.13% (< 35 Ys), 0.35% (35–40 Ys), 0.36% (41–50 Ys), 0.25% (51–60 Ys) and 0.098% (> 60Y s), which was statistically significant (p value = 0.04,0.60). Without dysplasia 0.19% (< 35 Ys), 0.5% (35–40 Ys), 0.56% (41–50 Ys), 0.51 (51–60 Ys) and 0.26% (> 60 Ys). There is no significance between occurrence of cervical dysplasia and without dysplasia despite of detection of HPV-HR subtypes (p value = 0.1754). The only use of HPV-subtyping is not a secure method and a protective way for women. There are worldwide many HPV-positive cases, which have been psychologically impaired with higher costs, although they have no cervical epithelial changes during the HPV-infection. There are many HPV-negative cases, in some studies up to 13% of cases, which develop cervical cancer. We have the opinion and are convinced that the screening should be both morphologically via cytological examination and may be with adding immunocytochemistry to detect the really dysplastic cervical lesions. HPV-subtyping may be added every three years to detect the concomitant subtype.

Focused ultrasound for high-risk human papillomavirus infection-related low-grade cervical lesions: a prospective cohort study

Objectives To assess the efficacy and safety of focused ultrasound (FU) for high-risk human papillomavirus (HR-HPV) infection-related cervical low-grade squamous intraepithelial lesions (LSIL). Methods Of 185 patients who met the inclusion criteria for this prospective study from October 2020 to November 2021, 95 received FU and 90 were followed up only. At the six-month follow-up, the HR-HPV clearance and LSIL regression rates of the groups were compared and factors affecting HR-HPV clearance were analyzed. The safety and side effects of FU were evaluated. Results No significant difference was found in the baseline clinical data between the two groups (p > 0.05). At the six-month follow-up, the HR-HPV clearance rates were 75.6% in the FU group and 25.6% in the observation group (p = 0.000). The LSIL regression rates were 89.5% in the FU group and 56.4% in the observation group (p = 0.000). Multivariate logistic regression analysis showed that the HR-HPV clearance rate in the FU group was 9.03 times higher than that in the observation group (95% confidence interval [CI], 3.75–21.73, p = 0.000), and the clearance rate of single-type HR-HPV infections was 5.28 times higher than that of multi-type infections (95% CI, 1.83–15.23, p = 0.002). The mean intraoperative bleeding was 1.8 ± 0.6 (1–3) mL; the mean intraoperative pain score was 2.6 ± 1.0 (1–6). Conclusions For patients with HR-HPV infection-related histological LSIL, FU can eliminate HR-HPV infection and cause lesions to regress in a short time, with few adverse effects and good tolerance.

Efficacy of a Coriolusversicolor-Based Vaginal Gel in Human Papillomavirus-Positive Women Older Than 40 Years: A Sub-Analysis of PALOMA Study.

In the PALOMA trial, Papilocare® demonstrated efficacy in repairing low-grade cervical lesions related to human papillomavirus (HPV). This sub-analysis aimed to evaluate its efficacy in repairing these cervical lesions and clearing HPV in women aged older than 40 years. This was a multicenter, randomized, open-label, parallel-group, controlled clinical trial. Patients with low-degree HPV-dependent cervical lesions receiving 6-month treatment with the vaginal gel were compared to those with a watchful waiting approach. Among the 41 women analyzed (aged 47.7 years), 31 presented high-risk (HR) oncogenic HPV subtypes, and 14 had 16-18-31 HPV genotypes. After 6 months, normalized cytology and concordant colposcopy were achieved by a greater percentage of treated women. The difference was significant in the total population (92.3% vs. 50.0%, p = 0.007), and HR-HPV subpopulation (90.5% vs. 33.3%, p = 0.003). In the HR HPVs-16-18-31 subpopulation, the values were 75.0% and 40.0% (p = 0.293). In the total population, 61.5% of treated patients obtained HPV clearance, compared to 50.0% in the control group. Regarding the HR-HPV subpopulation, these values were 66.7% and 44.4%, respectively. Papilocare® demonstrated significant efficacy in repairing low-degree HPV-related cervical lesions and a positive trend to clear HPV in women older than 40 years old in comparison to the watchful waiting approach.

Communications Is Time for Care: An Italian Monocentric Survey on Human Papillomavirus (HPV) Risk Information as Part of Cervical Cancer Screening.

Human papilloma virus (HPV) infection could be considered a social disease, both for its high incidence, especially in younger subjects, and for the risk of neoplastic evolution linked to viral infection. Therefore, the National Health System, in collaboration with the state, must help women to understand the oncological risk of HPV and suitable methods of prevention. We conducted an Italian monocentric survey on HPV risk information as part of cervical cancer screening. An anonymous questionnaire was administered to 200 women with high-risk positive HPV and low-grade cervical lesions during second-level cervical cancer screening at the Gynecology and Obstetrics Unit of the “San Paolo” Hospital. From this survey, the need to improve communication for patients has emerged, as currently it is not exhaustive. In response to this need, organizational changes have been implemented to centralize the moment of counseling in the second levels of screening and to improve the training of health workers in level I as well as family doctors. In addition, psychological support was also proposed to patients who requested it, as was the dissemination of material such as that produced by GISCI (Italian Cervico-Carcinoma Screening Group) and updated in May 2018, which provides 100 answers to questions on HPV in order to achieve effective and comprehensive communication. This investigation requires further development, and the expansion of this investigation to the multicenter level is already underway. Therefore, this survey will represent a cornerstone for further discussion on the topic considering the necessity of appropriate communication in the oncological context.

The Modeling Analysis and Effect of CHI3L1 and CD31-Marked Microvessel Density in the Occurrence and Development of Cervical Squamous Cell Carcinoma.

Background Chitinase-3-like protein 1 (CHI3Ll) has been identified as a novel tumor marker in several cancers. The objective of this study was to detect the expression of Chitinase-3-like protein 1 (CHI3L1) and CD31-labeled microvessel density (MVD) in cervical squamous cell carcinoma (CSCC) and to assess its prognostic impact. Methods Elivision™ plus immunohistochemical method was used to detect CHI3L1 expression and MVD in different cervical tissues. We analyzed the relationship between CHI3L1 and MVD in CSCC tissues and investigated the relationship between CHI3L1, MVD, and clinicopathological parameters. Univariate and multivariate survival analyses were performed to assess the impact on progression-free survival (PFS) and overall survival (OS). Results The positive expression rate of CHI3L1 protein in CSCC tissues (69.9%, 72/103) was significantly higher than that in high-grade cervical intraepithelial lesions (53.3%, 32/60), low-grade cervical intraepithelial lesions (25%, 15/60), and normal cervical tissues (16.7%, 10/60). MVD values ranged from 6 to 64 in CSCC, and no microvascular formation was observed in normal cervical tissues, high-grade intraepithelial lesions, or low-grade intraepithelial lesions. The high expression of CHI3L1 and MVD was significantly correlated with the invasion depth, differentiation degree, vascular invasion, and lymph node metastasis of CSCC (all P < 0.05). In CSCC, the expression of MVD in the CHI3L1 high-expression group (41.35 ± 9.056) was significantly higher than that in the CHI3L1 low-expression group (23.26 ± 11.000, P < 0.05). On univariate Kaplan–Meier analysis, FIGO stage, tumor diameter, lymph node metastasis, vascular invasion, CHI3L1, and MVD of CSCC were related to the prognosis of PFS and OS (all P < 0.05); however, CHI3L1 and MVD were not independent prognostic factors. Conclusion CHI3L1 may be involved in the progression of cervical cancer. Its high expression can promote neovascularization in the tumor microenvironment. CHI3L1 is a potential therapeutic target in the context of cervical cancer.

Risk of Cervical Cancer in Inflammatory Bowel Disease: A Meta-Analysis of Population-Based Studies.

There is increased risk of several malignancies in inflammatory bowel disease (IBD). However, evidence regarding risk of cervical cancer in IBD is conflicting. We aimed to investigate the risk of cervical cancer in IBD by undertaking a systematic review and meta-analysis of unselected, population-based studies. MEDLINE, EMBASE, and Cochrane Library were searched using Medical Subject Heading terms, and 2 reviewers independently screened results. Pooled hazard ratios (HRs) were calculated using random effects model meta-analysis for risk of cervical cancer in IBD. Subgroup meta-analysis was undertaken to assess risk of cervical cancer by IBD subtype (Crohn's disease and ulcerative colitis), treatment exposure, and grade of lesion. We screened 1,393 articles to identify 5 population-based studies, including 74,310 patients with IBD and 2,029,087 reference patients, across 5 different countries. Pooled random effects model meta-analysis of these studies did not show statistically significant increased risk for cervical cancer in IBD compared with reference populations (HR: 1.24; 95% confidence interval [CI]: 0.94-1.63). Meta-analysis by grade of lesion showed increased risk of low-grade cervical lesions (HR: 1.15; 95% CI: 1.04-1.28). Meta-analysis by disease subtype indicated no statistically significant increased risk in Crohn's disease (HR: 1.36; 95% CI: 0.83-2.23) or ulcerative colitis (HR: 0.95; 95% CI: 0.72-1.25) or in patients treated with antitumor necrosis factor (HR: 1.19; 95% CI: 0.64-2.21) or thiopurines (HR: 0.96; 95% CI: 0.60-1.50). This meta-analysis of high-quality, unselected population-based studies shows no statistically significant increased risk of cervical cancer in patients with IBD. There is, however, increased risk of low-grade cervical lesions compared with the general population.

Re-Evaluating the Predictive Values of Pap-smear for Diagnosis and LLETZ Margin Status for Management of Precancerous Cervical Lesions

Background: The incidence of HPV infection, precancerous cervical lesions and cervical cancer is relatively high in sub-Saharan African countries. There is significant variability among such countries and worldwide in the accuracy of screening for precancerous cervical lesions and test for cure after excision. Implementation and interval between these procedures also vary. Objective: The aim of this study was to determine the predictive values of Pap-smear for screening and LLETZ for proof-of-cure in a South African hospital setting. Patients and Methods: In the current study, the positive and negative predictive values of Pap-smear screening for the identification of low-grade and high-grade squamous epithelial cervical lesions (LSIL and HSIL, respectively) and Large Loop Excision of the Transformation Zone (LLETZ) procedures for the assessment of residual lesions were determined in a South African hospital setting. Patients referred to the hospital because of abnormal Pap-smear results were included. Results: Pap-smear screening was found to have a positive predictive value of over 90% for HSIL, indicating that this procedure is a reasonable low-cost method of screening for cervical cancer in this setting. Conversely, LLETZ displayed more modest PPV and NPV of 58% and 62%, respectively, for prediction of residual and completely excised lesions. Conclusion: Pap-smear testing had reasonable PPV (>90% for HSIL) to be effectively used as a low-cost screening method in a middle- to low-income South African hospital setting. The predictive values of LLETZ margin status was questionable, justifying careful follow-up after negative margin status. These results justify the consideration of post-LLETZ follow up pap-smear within 3–4 months for both positive and negative margin status, this may prevent under or over treatment of women with precancerous cervical lesions.

In silico screening and molecular dynamics simulations toward new human papillomavirus 16 type inhibitors.

Background and purpose:Human papillomavirus (HPV) is known as the main reason for cervical cancer. According to carcinogenic risk, HPV can be located into two classes, counting the low-risk virus, which is the main cause of genital warts and low-grade cervical epithelial lesions. HPV-16 is one of the high-risk HPV subtypes in the spectrum of cervical diseases.Experimental approach:The PubChem database was screened in order to identify potential anti-HPV hits followed by ADMET predictions. Then, molecular docking was performed to improve the accuracy of screening and also to find the details of the interactions of the hit compounds with the active site. Finally, molecular dynamic (MD) simulations and free binding energy on top-ranked structures CID_73212812, CID_91059286, CID_69838075, cidofovir, and jaceosidin were carried out with protein to compute the interaction energies and stability of the top-ranked compounds at the active site.Findings/Results:Based on molecular docking studies, three compounds including CID_73212812, CID_91059286, and CID_69838075 exhibited the best results among compounds against the E6 protein of HPV-16. Furthermore, RMSD, RMSF, hydrogen binds, Rg, and energy analysis during MD simulation certainly indicated the stable binding of selected compounds with E6 protein of HPV-16 active site.Conclusion and implications:Docking and MD results revealed that hydrophobic contacts and optimum hydrogen bonds were determinant factors in the interactions of hits and the E6 protein of HPV-16. In addition, the binding energy portions exposed that Van der Waals and non-polar interactions were fundamental factors in the molecule binding.