Intravaginal artesunate pessaries for treatment of cervical intraepithelial neoplasia 2/3 among HIV-positive and HIV-negative women in Kenya: Study protocol for a pilot trial.

Background: Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), which bear 90% of deaths. Current precancer treatments rely on healthcare workers who may be out of reach for many women. Development of a patient-controlled cervical precancer treatment can significantly improve access in remote areas and promote secondary prevention of cervical cancer. Methods: This is a phase I trial among 18 HIV-positive and HIV-negative women in Kenya, investigating use of artesunate vaginal pessaries as treatment for cervical precancer among women screening positive for cervical precancer who need excisional treatment. The primary objective will be the safety of self-administered artesunate pessaries. Participants will self-administer 200mg of artesunate vaginally daily for 5 days, followed by a drug-free week, repeated for a total of 4 cycles (artesunate self-administration on weeks 1, 3, 5, 7). The total study duration, including participant follow-up is 48 weeks. Safety and adherence will be assessed through review of symptom diaries and biweekly follow-ups during the treatment phase. Data analysis will include quantitative and qualitative methods. Figure 1 illustrates the study schema. Discussion: Considering the challenges associated with excisional treatments for cervical precancer in LMICs where access to care is limited, this study proposes an alternative approach using intravaginal Artesunate. This clinical trial will provide important safety and efficacy data on using artesunate as a topical therapy for both HIV-positive and HIV-negative women. Trial Registration: ClinicalTrials.gov identifier: NCT06165614.

Accuracy of GynTect® Methylation Markers to Detect Recurrent Disease in Patients Treated for CIN3: A Proof-of-Concept Case-Control Study.

Post-treatment follow-up in women with CIN3 is mandatory due to relapse in up to 15% of patients within 2 years. Standard follow-up care based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our proof-of-concept case-control study was to evaluate the performance of the methylation test GynTect® for the detection of recurrent CIN2/3 during follow-up. Residual clinical material from a recent, prospective, multicenter, observational study was available for further analysis. We studied a sample of 17 cases with recurrent CIN2/3 diagnosed within 24 months of follow-up and 31 controls without recurrence. DNA from cervical scrapes at baseline (immediately before CIN3 surgery) and up to three follow-up visits were analyzed for hrHPV and GynTect® methylation status. Cytology data were available from the previous study. Overall, 12 cases and 21 controls were GynTect-positive at baseline. In these subgroups, single test sensitivity at first follow-up was 67% (95% CI 39-87%) for GynTect® compared to 83% (95% CI 55-96%) for hrHPV (p = 0.50). Single test specificity was significantly higher for GynTect® (90%, 95% CI 71-98% vs. 62%, 95% CI 40-80%) (p = 0.03). In a co-testing setting, both hrHPV/cytology and GynTect®/cytology detected all recurrences. Specificity for GynTect®/cytology was higher than for hrHPV/cytology, but this difference was not statistically significant. In conclusion, for initially GynTect-positive patients, both hrHPV and GynTect® tests detected recurrent disease with similar sensitivity, but the GynTect® assay has a higher specificity. Incident hrHPV infection and/or persisting multifocal hrHPV infections without clinical disease are most likely responsible for the poorer specificity of the hrHPV test. A future prospective validation study will have to show whether GynTect®/cytology co-testing can outperform hrHPV/cytology co-testing in post-treatment surveillance.

The impact of Germany's human papillomavirus immunization program on HPV-related anogenital diseases: a retrospective analysis of claims data from statutory health insurances.

PURPOSE: Human papillomavirus (HPV) is the most common sexually transmitted infection, responsible for multiple HPV-related diseases, including almost all cervical cancers. The highly effective HPV vaccination has been recommended under the German HPV national immunization program (NIP) since 2007 and is reimbursed by health insurances. Vaccination uptake rates, however, remain suboptimal and data on the real-world impact of HPV vaccination in Germany are lacking. This study aims to demonstrate the population-level impact of Germany's NIP on HPV-related anogenital diseases among young women. METHODS: Retrospective claims data analysis using a classic impact study design comparing disease prevalence among 28- to 33-year-old women before and after introduction of the HPV-immunization program in Germany. Claims data representing approximately two thirds of German health insurances were used. HPV-related disease outcomes included cervical cancer and high grade precancers (cervical intraepithelial neoplasia (CIN) 2+), anogenital warts, as well as vulvar, vaginal, and anal precancer/cancer. RESULTS: Significant declines were seen for CIN2+, anogenital warts, and vaginal precancer/cancer. Prevalence of CIN2+ declined 51.1% from 0.92% (95% CI = 0.78%, 1.08%) to 0.45% (95% CI = 0.38%, 0.53%). There was a 38.6% decline in anogenital warts prevalence from 0.44% (95% CI = 0.36%, 0.54%) to 0.27% (95% CI = 0.22%, 0.32%) and 75.0% decline in vaginal precancer/cancer prevalence from 0.04% (95% CI = 0.02%, 0.07%) to 0.01% (95% CI = 0.00%, 0.02%). CONCLUSION: The German HPV-immunization program has led to significant declines in female anogenital disease among young women in Germany, highlighting the importance of the vaccination. Moreover, the data suggest that increasing vaccination coverage in Germany could further strengthen the public-health impact of its HPV-immunization program.

Exploring serum trace element shifts: Implications for cervical intraepithelial neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) represents a premalignant state presumably related to perturbations in circulating levels of trace elements. MATERIALS AND METHODS: Employing inductively coupled plasma mass spectrometry (ICP-MS), we quantified essential and toxic trace elements in the sera of 60 women diagnosed with CIN and 60 age-matched healthy counterparts. RESULTS: Our investigation revealed a noteworthy higher levels in serum of Mn, Zn, and Pb, as well as lower levels in Ni, Se, Rb, and Mo levels within the CIN cohort. Levels of Mn, Zn, and Pb were higher by approximately 5.5-fold, 3.0-fold, and 7.5-fold, respectively, while Mo levels exhibited an approximate 4.5-fold reduction in CIN sera compared to the control group. While the study provided valuable insights into trace element variations, it's important to note that the adult Serbian population is considered Zn-deficient, so the Zn data should be interpreted with caution. Age stratification (30-40 vs. 40-50 vs. 50-60 years), smoking status (smokers vs. nonsmokers), and CIN severity (CIN 2 vs. CIN 3) yielded no significant disparities in elemental profiles. Among the 10 proposed ratios, 5 demonstrated a significant surge in CIN sera relative to controls: Mn/Se, Mn/Mo, Zn/Se, Zn/Mo, and Se/Mo. Correlation analysis of trace element levels revealed a predominantly consistent pattern between CIN cases and healthy subjects, except for Zn and its negative correlations (antagonistic interactions) with other analyzed trace elements. CONCLUSION: Our findings underscore differences in serum levels of specific trace elements in CIN cases versus controls, implicating their potential involvement in the underlying pathophysiological cascades culminating in cervical neoplasms.

RAP1-GTPase immunostaining is altered in human precancerous and cancerous cervical lesions.

Aim: This study investigated RAP1 immunostaining variation in different cell types during CC progression.Methods: Paraffin-embedded cervical tissues from 101 patients were categorized into control, pre-neoplastic and neoplastic groups. RAP1 immunolocalization, HPV detection and genotyping were performed. A semiquantitative immunoreactive score was employed to compare labeling intensity, cellular localization, nuclear labeling, percentage and distribution of reactive cells.Results: 73% (72/99) of cervical specimens were HPV+. RAP1 was localized in the nucleus and cytoplasm of all samples. Cytoplasmic RAP1 immunoscore was higher than nuclear score in all CC groups. RAP1 intensity increased with lesion severity. SCC samples exhibited predominantly intense RAP1 immunostaining.Conclusion: RAP1 is an efficient biomarker for detecting invasive CC lesions but has limited utility in distinguishing SCC grades.

[Box: see text].

Distribution and diagnostic value of single and multiple high-risk HPV infections in detection of cervical intraepithelial neoplasia: A retrospective multicenter study in China.

The risk associated with single and multiple human papillomavirus (HPV) infections in cervical intraepithelial neoplasia (CIN) remains uncertain. This study aims to explore the distribution and diagnostic significance of the number of high-risk HPV (hr-HPV) infections in detecting CIN, addressing a crucial gap in our understanding. This comprehensive multicenter, retrospective study meticulously analyzed the distribution of single and multiple hr-HPV, the risk of CIN2+, the relationship with CIN, and the impact on the diagnostic performance of colposcopy using demographic information, clinical histories, and tissue samples. The composition of a single infection was predominantly HPV16, 52, 58, 18, and 51, while HPV16 and 33 were identified as the primary causes of CIN2+. The primary instances of dual infection were mainly observed in combinations such as HPV16/18, HPV16/52, and HPV16/58, while HPV16/33 was identified as the primary cause of CIN2+. The incidence of hr-HPV infections shows a dose-response relationship with the risk of CIN (p for trend <0.001). Compared to single hr-HPV, multiple hr-HPV infections were associated with increased risks of CIN1 (1.44, 95% confidence interval [CI]: 1.20-1.72), CIN2 (1.70, 95% CI: 1.38-2.09), and CIN3 (1.08, 95% CI: 0.86-1.37). The colposcopy-based specificity of single hr-HPV (93.4, 95% CI: 92.4-94.4) and multiple hr-HPV (92.9, 95% CI: 90.8-94.6) was significantly lower than negative (97.9, 95% CI: 97.0-98.5) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+). However, the sensitivity of single hr-HPV (73.5, 95% CI: 70.8-76.0) and multiple hr-HPV (71.8, 95% CI: 67.0-76.2) was higher than negative (62.0, 95% CI: 51.0-71.9) in detecting HSIL+. We found that multiple hr-HPV infections increase the risk of developing CIN lesions compared to a single infection. Colposcopy for HSIL+ detection showed high sensitivity and low specificity for hr-HPV infection. Apart from HPV16, this study also found that HPV33 is a major pathogenic genotype.

Advancements in the Management of Cervical Intraepithelial Neoplasia: A Comprehensive Review.

Cervical intraepithelial neoplasia (CIN) represents a significant precursor to cervical cancer, posing a considerable threat to women's health globally. This comprehensive review examines recent advancements in the management of CIN, encompassing screening, diagnosis, and treatment modalities. The etiology and pathogenesis of CIN are explored alongside an analysis of traditional and emerging screening techniques, including liquid-based cytology and molecular biomarkers. Treatment options, from minimally invasive procedures to immunotherapy approaches, are evaluated for efficacy and potential impact on patient outcomes. Furthermore, this review highlights the implications of these findings for clinical practice, emphasizing the importance of staying abreast of evolving guidelines and integrating innovative strategies into routine care. Recommendations for future research and practice are provided, emphasizing personalized approaches, disparities in access to care, and the exploration of novel therapeutic avenues. By addressing these challenges and opportunities, this review aims to contribute to the ongoing efforts to mitigate the burden of CIN and cervical cancer, ultimately improving women's health outcomes worldwide.

Impact of HPV Vaccination on the Incidence of High-Grade Cervical Intraepithelial Neoplasia (CIN2+) in Women Aged 20-25 in the Northern Part of Norway: A 15-Year Study.

BACKGROUND: Human papillomavirus (HPV), the most prevalent sexually transmitted infection globally, is a key risk factor for high-grade cervical lesions and cervical cancer. Since 2009, HPV vaccination has been part of the national immunization program for girls in 7th grade in Norway (women born 1997 and later). This study aimed to assess the impact of HPV vaccination on the incidence of high-grade cervical precursors (CIN2+) among women aged 20-25 in Troms and Finnmark over a 15-year period. MATERIALS AND METHODS: In this time series study, we analyzed cervical screening data from 15,328 women aged 20-25 in Troms and Finnmark, collected between 2008 and 2022. Statistical methods, including linear and logistic regression, were employed to evaluate changes in cervical intraepithelial neoplasia grade 2 and worse (CIN2+) incidence and compare risks between vaccine-offered cohorts and pre-vaccine cohorts. RESULTS: The incidence of CIN2+ initially increased from 31 cases per year in 2008 to 110 cases in 2018, then significantly decreased to 44 cases per year by 2022 (p < 0.01). Women in pre-vaccine cohorts had a substantially higher risk of CIN2+ (OR 9.02, 95% CI 5.9-13.8) and CIN3+ (OR 19.6, 95% CI 7.3-52.6). Notably, no vaccinated women with CIN2+ tested positive for HPV types 16 or 18. Furthermore, none of the 13 cervical cancer cases recorded during the study were from the vaccinated cohorts. INTERPRETATION: The findings suggest a significant reduction in the incidence of high-grade cervical precursors following the introduction of the HPV vaccine in Norway's national immunization program, highlighting its effectiveness in cervical cancer prevention among young women in Northern Norway.

YAP/TAZ-TEAD activity promotes the malignant transformation of cervical intraepithelial neoplasia through enhancing the characteristics and Warburg effect of cancer stem cells.

A number of studies have confirmed that Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)-transcriptional enhanced associate domain (TEAD) activity is the driver of cancer development. However, the role and mechanism of the YAP/TAZ-TEAD pathway in cervical intraepithelial neoplasia (CIN) remain to be clarified. Therefore, this study was designed to observe the effect of YAP/TAZ-TEAD activity on the development of CIN and provide new ideas for the diagnosis and treatment of CIN. Firstly, cervical tissues were collected from CIN patients in different stages [CIN grade 1 (CIN1) tissue, CIN grade 2/3 (CIN 2/3) and squamous cell carcinoma (SCC)] and healthy volunteers. Next, the expression levels of YAP, TAZ and TEAD in cervical tissues and cells were observed by immunohistochemistry, qRT-PCR and western blot. Besides, Z172 and Z183 cells were transfected with siRNA-YAP/TAZ (si-YAP/TAZ) and YAP/TAZ overexpression vector (YAP-5SA). Also, Z172 cells were co-transfected with YAP-5SA and si-TEAD2/4. Subsequently, the stemness characteristics, glycolysis level and malignant transformation of cells in each group were observed by sphere-formation assay, commercial kit, MTT, Transwell, scratch experiment, xenotransplantation and western blot.The expression of YAP, TAZ and TEAD increased significantly in cervical cancer tissue and cell line at the stage of CIN2/3 and SCC. When YAP/TAZ was knocked down, the stemness characteristics, glycolysis level and malignant transformation of cancer cells were notably inhibited; while activating YAP/TAZ exhibited a completely opposite result. In addition, activating YAP/TAZ and knocking down the TEAD expression at the same time significant weakened the effect of activated YAP/TAZ signal on precancerous cells and reduced inhibitory effect of knocking down TEAD alone. YAP/TAZ-TEAD signal activates the characteristics and Warburg effect of cancer stem cells, thereby promoting the malignant transformation of CIN.

Knowledge of cytology results affects the performance of colposcopy: a crossover study.

OBJECTIVE: To determine whether knowledge of cytology affects the colposcopist's diagnostic accuracy in the identification of cervical intraepithelial neoplasia grade 2 and worse (≥ CIN2). METHOD: In this cross-over study, healthcare professionals interpreted colposcopy images from 80 patient cases with known histological diagnoses. For each case, 2 images taken with a colposcope were provided (native and after acetic acid application). Inclusion criteria consisted of women with a transformation zone type 1 or 2, who had both a cytological and histological diagnosis. Cases were distributed across two online surveys, one including and one omitting the cytology. A wash-out period of six weeks between surveys was implemented. Colposcopists were asked to give their diagnosis for each case as < CIN2 or ≥ CIN2 on both assessments. Statistical analysis was conducted to compare the two interpretations. RESULTS: Knowledge of cytology significantly improved the sensitivity when interpreting colposcopic images, from 51.1% [95%CI: 39.3 to 62.8] to 63.7% [95%CI: 52.1 to 73.9] and improved the specificity from 63.5% [95%CI: 52.3 to 73.5] to 76.6% [95%CI: 67.2 to 84.0]. Sensitivity was higher by 38.6% when a high-grade cytology (ASC-H, HSIL, AGC) was communicated compared to a low-grade cytology (inflammation, ASC-US, LSIL). Specificity was higher by 31% when a low-grade cytology was communicated compared to a high-grade. CONCLUSIONS: Our data suggests that knowledge of cytology increases sensitivity and specificity for diagnosis of ≥ CIN2 lesions at colposcopy. Association between cytology and histology may have contributed to the findings.

Immunotherapy that leverages HPV-specific immune responses for precancer lesions of cervical cancer.

Cervical cancer and its precursor lesion, cervical intraepithelial neoplasia (CIN), are caused by high-risk human papillomavirus (HPV) viral infection and are highly susceptible to host immunity targeting of HPV viral proteins, which include both foreign antigens and cancer antigens expressed by tumors. Immunotherapy that induces Th1 immunoreactivity against viral proteins is expected to take advantage of this immunological regression mechanism. However, although cancer immunotherapies for cervical cancer and CIN have been developed over the past several decades, none have been commercialized. Most of these immunotherapies target the viral cancer proteins E6 and E7, which are generally the same. The reasons for the underdevelopment of HPV-targeted immunotherapy differ depending on whether the target is invasive cancer or CIN. We here summarize the developmental history of cancer immunotherapy for CIN and discuss strategies for solving the problems that led to this underdevelopment. We note that CIN is a mucosal lesion and propose that inducing mucosal immunity may be the key.

Human Papillomavirus Infections and the Role Played by Cervical and Cervico-Vaginal Microbiota-Evidence from Next-Generation Sequencing Studies.

This comprehensive review encompasses studies examining changes in the cervical and cervico-vaginal microbiota (CM and CVM) in relation to human papillomavirus (HPV) using next-generation sequencing (NGS) technology. HPV infection remains a prominent global health concern, with a spectrum of manifestations, from benign lesions to life-threatening cervical cancers. The CM and CVM, a unique collection of microorganisms inhabiting the cervix/vagina, has emerged as a critical player in cervical health. Recent research has indicated that disruptions in the CM and CVM, characterized by a decrease in Lactobacillus and the overgrowth of other bacteria, might increase the risk of HPV persistence and the progression of cervical abnormalities. This alteration in the CM or CVM has been linked to a higher likelihood of HPV infection and cervical dysplasia. NGS technology has revolutionized the study of the cervical microbiome, providing insights into microbial diversity, dynamics, and taxonomic classifications. Bacterial 16S rRNA gene sequencing, has proven invaluable in characterizing the cervical microbiome, shedding light on its role in HPV infections and paving the way for more tailored strategies to combat cervical diseases. NGS-based studies offer personalized insights into an individual's cervical microbiome. This knowledge holds promise for the development of novel diagnostic tools, targeted therapies, and preventive interventions for cervix-related conditions, including cervical cancer.

Optimising cervical cancer screening during pregnancy: a study of liquid-based cytology and HPV DNA co-test.

This study assessed the efficacy of ThinPrep cytologic test and human papillomavirus (HPV) co-test in cervical cancer screening during pregnancy. A cohort of 8,712 pregnant women from Ren Ji Hospital participated in the study. Among them, 601 (6.90%) tested positive for high-risk HPV (HR-HPV) and 38 (0.44%) exhibited abnormal cytology results (ASCUS+). Following positive HR-HPV findings, 423 patients underwent colposcopy, and 114 individuals suspected of having high-grade squamous intraepithelial lesion and cervical cancer (HSIL+) underwent cervical biopsy. Histological examination revealed 60 cases of normal pathology (52.63%), 35 cases of low-grade squamous intraepithelial lesion (30.70%), 17 cases of HSIL (14.91%), and 2 cases of cervical cancer (1.75%). The incidence of HSIL+ in HPV 16/18 group was significantly higher than that in non-HPV16/18 group (10.53% vs. 6.14%, P < 0.05). Subsequent evaluation of the clinical performance of cytology alone, primary HPV screening, and co-testing for HSIL+ detection revealed that the HSIL+ detection rate was lowest with cytology alone. These findings suggest that HPV testing, either alone or combined with cytology, presents an efficient screening strategy for pregnant women, underscoring the potential for improved sensitivity in cervical cancer screening during pregnancy. The significantly higher incidence of HSIL+ in the HPV16/18 group emphasizes the importance of genotype-specific considerations.

HPV E6/E7 mRNA combined with thin-prep cytology test for the diagnosis of residual/recurrence after loop electrosurgical excision procedure in patients with cervical intraepithelial neoplasia.

To evaluate the diagnostic value of combining HPV E6/E7 mRNA testing with Thin-Prep cytology (TCT) for residual/recurrence detection, a total of 289 patients who underwent loop electrosurgical excision procedure (LEEP) for high-grade cervical lesions were included. Patients were followed up at different time points, and residual/recurrent lesions were confirmed through vaginoscopy. TCT, HPV-DNA, and HPV E6/E7 mRNA tests were conducted. Diagnostic performance, including sensitivity, specificity, positive predictive value, negative predictive value, and accuracy, was assessed. Among the patients, 76 cases showed residual lesions/recurrence, while 213 cases showed no residual/recurrence. Positive margins in the cervical-vaginal and cervical canal areas were associated with a higher risk of residual/recurrence. The combined HPV E6/E7 mRNA and TCT test showed higher diagnostic efficacy than individual tests at 6-, 12-, and 24-months follow-up. The combined test consistently demonstrated higher specificity and sensitivity, with significantly larger area under the curve (AUC) values compared to the individual tests.

Immediate histologic correlation in patients with different HPV genotypes and ages: a single center analysis in China.

BACKGROUND: Human papillomavirus (HPV) has been confirmed as a major causative factor for malignant transformation of cervical epithelial cells and for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. We carried out this study to investigate the association of different HPV genotypes and ages with immediate histological cervical lesions in opportunistic screening patients in a single center. METHODS: A total of 1,661 samples with biopsy-confirmed histologic findings were collected from the gynecological clinic of our hospital between October 2017 and May 2020 for analysis. The distribution of single-type HPV genotypes in CIN of different severities and the age-dependent prevalence for single-type HPV infection were analyzed. RESULTS: In both CIN2 and CIN3 group, HPV16, 58, 52, 33 and 31/18 were detected as top 5 high-risk human papillomavirus (hrHPV) types, which accounts for 89.25% and 88.54% of single HPV infection incidence respectively. Besides, not a single case of HPV45 was found in CIN2 and CIN3. HPV16 was the dominant genotype in both CIN2 and CIN3, accounted for 46.24% and 55.21%, respectively. The prevalence of HPV16 was the most frequent in all the age groups, except ≥ 65 years group in CIN3, and almost one in three HPV16-positive patients were diagnosed with high grade CIN. The peak of the incidence of CIN3 was observed at 25 ~ 34 years (33.68%), followed by 35 ~ 44 years (31.58%). CONCLUSION: High grade CIN peak at 25 ~ 44 years, women of this age are recommended for normative screening if conditions permit. HPV16-positive patients should be given high priority in opportunistic screening, while the single-center data suggesting a low risk of CIN2/3 in HPV45-positive patients. For women ≥ 65 years old, patients infected with other HPV types should be also taken seriously. In general, HPV16, 58, 52, 33, 31 and 18 were the most common genotypes in CIN2/3, and a vaccine including these predominant genotypes might be of great significance for cervical cancer prevention in China.

The Efficiency of Cervical Pap and Comparison of Conventional Pap Smear and Liquid-Based Cytology: A Review.

Cervical cancer is one of the leading health burdens globally with a huge incidence in developing countries like India. Cervical cancer has an extended premalignant stage known as cervical dysplasia or cervical intraepithelial neoplasia (CIN). CIN can be grade 1, 2, or 3 depending on its severity. One of the most effective methods of cervical cancer screening and prevention is detecting these premalignant lesions by cervical cytology. Pioneered by Dr. George Nicholas Papanicolaou, the Papanicolaou (Pap) stain became an important advent for the microscopic evaluation of the exfoliated cervical cells. Over the years, this method of conventional Pap smear became more practiced and yielded excellent results, so much so that the incidence of cervical cancer actually started to decline in developed countries. However, few drawbacks started to become evident with conventional Pap smears like unsatisfactory samples due to obscuring materials, false negative results due to sampling error, and low sensitivity. To overcome these drawbacks of conventional Pap smear, liquid-based cytology (LBC) was introduced in 1996. Thereafter, many investigations and studies have been conducted by many authors to compare the efficacy of conventional Pap smear and LBC. This review puts forward the facts and results of various studies pertaining to efficacy of cervical cytology, comparing conventional Pap smear and LBC, and highlighting the pros and cons of each method based on various studies. For this review, relevant articles under the headings "Conventional PAP smear", "Cervical cancer screening", "Liquid-based cytology" and "Comparison" have been searched in PubMed/MEDLINE and Google Scholar. About 100 articles were studied, and all the facts have been highlighted. While many studies did support LBC over conventional Pap smear for screening of cervical abnormalities, some studies did not find any major difference between the two and preferred the practice of conventional Pap smear in our Indian scenario considering the low-resource setting and low price. This research highlights the various facts of the two types of cervical Pap smear and their comparison.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

HPV genotype-specific distribution and attributable risk in cervical intraepithelial neoplasia in a referral population with a history of LSIL.

BACKGROUND AND OBJECTIVE: CINtec PLUS and cobas HPV tests (Roche) were previously ascertained for triaging an LSIL referral population [1]. As part of this study, genotype-specific distribution and attributable risk of high-risk (HR)-HPV in cervical intraepithelial neoplasia (CIN) were determined. METHODS: Archived cervical specimens in ThinPrep PreservCyt (Hologic Inc) from the LSIL referral population (n= 533) were genotyped using the Anyplex II HPV HR test (Anyplex, Seegene Inc). Since the study specimens had been in storage in ambient temperature for 31-47 months since collection, Anyplex results were compared with that of the initial cobas testing of fresh specimens to validate the suitability and stability of specimens for the present study. RESULTS: Overall, Anyplex test was positive in 63% (336/533) vs. 55.7% (297/533) for cobas test. Anyplex test performed identical to cobas test identifying 93.2% (82/88) of ⩾CIN2/adenocarcinoma in situ (AIS). Anyplex test detected genotypes 16/18 in 15.7% (36/230) ⩽CIN1 vs. 45.5% (40/88) ⩾CIN2/AIS; the corresponding figures were 13.5% (31/230) and 45.5% (40/48) for the cobas test. Genotype 16 showed increasing attribution, 13.2% in CIN1, 27.1% in CIN2 and 40% in CIN3/AIS. Of the 12 other high-risk (OHR) types collectively identified by cobas, Anyplex test specifically detected, in decreasing order, genotypes 51, 31, 35, 56, 39, and 45 as the most frequent types, often in multiple-type infections, in 64.8% ⩾CIN2. Regardless, estimated attribution was evident for each of the 12 OHR types in ⩾CIN2. Multiple-type infections were more frequent than single-type infections in all CIN grades. CONCLUSIONS: Attributable risk of all HR-HPV genotypes targeted by both Anyplex and cobas tests was evident in ⩾CIN2/AIS Testing for these genotypes in HPV primary cervical screening and cytology triage could identify those at increased risk of cervical cancer and also be beneficial in the management of LSIL referral populations.

Characteristics of vaginal microbiota in various cervical intraepithelial neoplasia: a cross-sectional study.

BACKGROUND: Precancerous lesions of cervical cancer exhibit characteristics indicative of natural progression. To prevent overtreatment of patients whose cervical intraepithelial neoplasia (CIN) in regression and to predict the onset of invasive cervical cancer at an early stage, we've identified the vaginal microbiome as a potential key factor, which is associated with both HPV infection and the various cervical intraepithelial neoplasia. This study aims to investigate the microbiome characteristics of patients with various cervical intraepithelial neoplasia. METHODS: Utilizing high-throughput 16S ribosomal RNA (16S rRNA) sequencing technology, a description of the characteristics and community composition of Vaginal Microbiota (VMB) was conducted among 692 Chinese women infected with the High-risk Human Papillomavirus (HR-HPV). RESULTS: As the grade of the lesions increased, the proportions of Lactobacillus and Pseudomonas demonstrated a significant declining trend, while the proportions of Gardnerella, Dialister, and Prevotella significantly increased. The diversity of the VMB was more significant in high-grade CIN. Furthermore, KEGG pathway enrichment analysis indicates that high-grade cervical intraepithelial neoplasia can inhibit various pathways, including those of phosphotransferase system, transcription factors, Fructose and mannose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism, which may contribute to the development of early cervical cancer symptoms. CONCLUSION: Patients with CIN exhibit a distinct vaginal microbial profile characterized by a decrease in Lactobacillus and Pseudomonas, and an increase in Gardnerella, Prevotella, and Dialister. The proliferation and diminution of these two types of microbial communities are interrelated, suggesting a mutual restraint and balance among them. Disruption of this regulatory balance could potentially lead to the onset of cervical lesions and carcinogenesis. Retrospectively registered: This study was approved by the Ethics Committee of the Beijing Chaoyang Hospital affiliated with the Capital Medical University (NO.2023-S-415).

Cervical Intraepithelial Neoplasia Grade 3 in the Third Trimester of Pregnancy: A Case Report.

The incidence of malignancies during pregnancy has been on the rise in the recent years, primarily due to an increase in older age pregnancies. This poses a significant risk to both the mother and the developing fetus. We present the case of a 29-year-old woman who experienced intermittent vaginal bleeding during her pregnancy. In the last trimester, the patient presented with abnormal vaginal bleeding and abdominal pain. The gestational age was 37.6 weeks. Notably, to our knowledge, there have been no reported cases of grade 3 cervical intraepithelial neoplasia in the third trimester.