Search

Objective Methods Results Conclusion To determine the safety, tolerance, and adherence to self‐administered intravaginal 5% fluorouracil (5FU) cream as adjuvant therapy following cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) treatment among women living with HIV (WLWH) in Kenya.A phase I pilot trial was performed among 12 WLWH in Kenya, aged 18–49 years between March 2023 and February 2024 (ClinicalTrial.gov NCT05362955). Participants self‐administered 2 g of 5FU intravaginally every other week for eight applications. Safety was assessed using a standardized grading scale, and adherence was evaluated using self‐report, inspection of used applicators, and weighing of the study drug.The mean age and CD4 count were 43.9 years and 781 cells/mm3, respectively. Seven (58%) had an eighth‐grade education or less. All 12 reported at least one grade I adverse event (AE), one (8%) reported a grade 2 AE, no grade 3 or 4 AEs were reported. Increased vaginal discharge (n = 9, 75%) and irritation (n = 5, 42%), with a mean duration of 3.2 and 2.8 days, respectively, were the most commonly reported AEs. Provider‐observed AEs included grade 1 cervical erythema and superficial abrasions. All participants tolerated all eight 5FU doses, and 96% adherence was demonstrated.Self‐administered 5FU following CIN2/3 treatment among WLWH in Kisumu, Kenya, was safe, tolerable, and associated with high adherence. Randomized trials are needed to investigate whether adjuvant 5FU can improve treatment outcomes or serve as primary cervical precancer treatment in sub‐Saharan Africa. A self‐administered therapy may be transformative in increasing access to treatment and, hence, secondary prevention of cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Trichomonas vaginalis infection is the most prevalent non‐viral sexually transmitted infection (STI) in women and has been suggested as a risk factor for developing cervical cancer. Objective: We aimed to investigate the associations between T. vaginalis infection and cervical carcinogenesis. Search Strategy: A comprehensive systematic search was conducted in five databases on 21 October 2021. Selection Criteria: Studies assessing the relationship between T. vaginalis infection, HPV co‐infections, cervical dysplasia, and cervical cancer were found eligible. Data Collection and Analysis: Summary estimates for pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated with a random‐effects model. Statistical heterogeneity was measured with I2 and Cochran's Q tests. Main Results: The 29 articles included 473 740 women, of whom 8518 were T. vaginalis‐positive. Our results showed that T. vaginalis‐infected women had 1.79 times higher odds of being diagnosed with HPV co‐infection (95% CI 1.27–2.53; I2 95%). We also found that T. vaginalis infection was associated with high‐grade squamous intraepithelial lesion diagnosis (OR 2.34, 95% CI 1.10–4.95; I2 75%) and cervical cancer (OR 5.23, 95% CI 3.03–9.04; I2 3%). Conclusions: Our results showed an association between T. vaginalis and cervical carcinogenesis in sexually active women. Synopsis: We found an association between Trichomonas vaginalis and cervical carcinogenesis; in the case of Trichomonas detection, cervical dysplasia should be considered for evaluation. [ABSTRACT FROM AUTHOR]

High‐grade cervical intraepithelial neoplasia (CIN2 and CIN3) represents a heterogeneous disease with varying cancer progression risks. Biomarkers indicative for a productive human papillomavirus (HPV) infection (HPV E4) and a transforming HPV infection (p16ink4a, Ki‐67 and host‐cell DNA methylation) could provide guidance for clinical management in women with high‐grade CIN. This study evaluates the cumulative score of immunohistochemical expression of p16ink4a (Scores 0‐3) and Ki‐67 (Scores 0‐3), referred to as the "immunoscore" (IS), in 262 CIN2 and 235 CIN3 lesions derived from five European cohorts in relation to immunohistochemical HPV E4 expression and FAM19A4/miR124‐2 methylation in the corresponding cervical scrape. The immunoscore classification resulted in 30 lesions within IS group 0‐2 (6.0%), 151 lesions within IS group 3‐4 (30.4%) and 316 lesions within IS group 5‐6 (63.6%). E4 expression decreased significantly from CIN2 to CIN3 (P <.001) and with increasing immunoscore group (Ptrend <.001). Methylation positivity increased significantly from CIN2 to CIN3 (P <.001) and with increasing immunoscore group (Ptrend <.001). E4 expression was present in 9.8% of CIN3 (23/235) and in 12.0% of IS group 5‐6 (38/316). Notably, in a minority (43/497, 8.7%) of high‐grade lesions, characteristics of both transforming HPV infection (DNA hypermethylation) and productive HPV infection (E4 expression) were found simultaneously. Next, we stratified all high‐grade CIN lesions, based on the presumed cancer progression risk of the biomarkers used, into biomarker profiles. These biomarker profiles, including immunoscore and methylation status, could help the clinician in the decision for immediate treatment or a "wait and see" policy to reduce overtreatment of high‐grade CIN lesions. What's new? Treating all high‐grade cervical intraepithelial neoplasia (CIN2/3) with excisional therapy leads to overtreatment, as these lesions have varying cancer progression risks. Here, the authors evaluated expression patterns of p16ink4a, Ki‐67 and the HPV E4 protein, and methylation of FAM19A4/miR124‐2 in high‐grade CIN. The biomarker expression patterns revealed the high degree of heterogeneity among CIN2/3 lesions. Biomarker profiles based on the presumed cancer progression risks were established and could guide clinicians in choosing whether to treat immediately or wait and see. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the outcomes of cryotherapy and thermo‐coagulation in the treatment of cervical precancers. Method: Prospective analytical study. Women who screened positive to visual inspection with acetic acid and confirmed by colposcopy using the Swede's score were randomized to receive either cryotherapy or thermo‐coagulation. Participants were re‐evaluated 6 months later. Results: A total of 11 124 women were screened. Only 1023 of the 1294 colposcopically confirmed positive cases were eligible for ablative therapy. Five hundred and twelve women received cryotherapy while 511 women received thermo‐coagulation. Cryotherapy had similar cure rate with thermo‐coagulation (85.5 vs 89.2%, P = 0.09). The mean patient satisfaction score for thermo‐coagulation was higher than that for cryotherapy (3.9 ± 1.3 vs 2.8 ± 1.7; P < 0.0001). The mean duration of treatment per patient was higher for cryotherapy than thermo‐coagulation (660.0 ± 0.0 vs 50.9 ± 15.3 s, P < 0.0001). The mean cost of treatment per patient was significantly higher for cryotherapy than for thermo‐coagulation (2613.1 ± 254.9 vs 533.2 ± 45.2 Nigerian Naira, P < 0.0001). Higher proportion of women who had thermo‐coagulation reported no side effect (55.2 vs 12.5%, P < 0.0001). Conclusion: Cryotherapy and thermo‐coagulation have similar efficacy in the treatment of cervical precancers. Thermo‐coagulation offers lower cost and lower duration of treatment, less side effects and higher patient satisfaction than cryotherapy. Thermo‐coagulation should be the recommended ablative treatment method for low‐resource settings of the world. [ABSTRACT FROM AUTHOR]

Precancerous cervical lesions precede the development of invasive cervical cancer by 10-20 years, making cervical cancer preventable if these lesions are detected and effectively treated. Treatment has evolved in the last few decades and now includes ablative options that can be performed in lower-resource settings where surgical excision is not feasible or routinely available. Gas-based cryotherapy, which freezes cervical tissue to induce localized necrosis, is the most commonly used ablative treatment. However, its implementation in low-resource settings is difficult because the refrigerant gas can be difficult to procure and transport, and is expensive. New cryotherapy devices that do not require an external supply of gas appear promising. Thermal coagulation, which burns cervical tissue to induce necrosis, has become more widely available in the last few years owing to its portability and the feasibility of using battery-powered devices. These two ablative treatments successfully eradicate 75%-85% of high-grade cervical lesions and have minor adverse effects. [ABSTRACT FROM AUTHOR]

We have developed and evaluated a next-generation bisulfite sequencing (NGS) assay to distinguish HPV16 cervical precancer (CIN2-3; N =59) from HPV16-positive transient infections ( N = 40). Cervical DNA was isolated and treated with bisulfite and HPV16 methylation was quantified by ( i) amplification with barcoded primers and massively parallel single molecule sequencing and ( ii) site-specific pyrosequencing. Assays were evaluated for agreement using intraclass correlation coefficients (ICC). Odds ratios (OR) for high methylation vs. low methylation were calculated. Single site pyrosequencing and NGS data were correlated (ICC = 0.61) and both indicated hypermethylation was associated with precancer (ORs of 2-37). Concordant NGS and pyrosequencing results yieled ORs that were stronger when compared with using either assay separately. Within the L1 region, the ORs for CIN2-3 were 14.3 and 22.4 using pyrosequencing and NGS assays, respectively; when both methods agreed the OR was 153. NGS assays provide methylation haplotypes, termed methyl-haplotypes from single molecule reads: cases had increased methyl-haplotypes with ≥ 1 methylated CpG site(s) per fragment compared with controls, particularly in L1 ( p = 3.0 × 10−8). The maximum discrimination of cases from controls for a L1 methyl-haplotype had an AUC of 0.89 corresponding to a sensitivity of 92.5% and a specificity of 73.1%. The strengthening of the OR when the two assays were concordant suggests the true association of CpG methylation with precancer is stronger than with either assay. As cervical cancer prevention moves to DNA testing methods, DNA based biomarkers, such as HPV methylation could serve as a reflex strategy to identify women at high risk for cervix cancer. [ABSTRACT FROM AUTHOR]

Interactions of carcinogenic human papillomaviruses (most notably HPV types 16/18/31/33/45), and HPV6 or Chlamydia trachomatis are not well understood. We have used seroconversions to study effects the order of these infections has on the risk of high-grade cervical precancer. In a cohort of 94,349 Finnish women with paired sera from consecutive pregnancies within an average of 2.4 years, 490 were diagnosed with cervical CIN3/AIS. Serum antibodies to HPV6/16/18/31/33/45 and C. trachomatis were measured in paired sera of the cases and a subcohort of 2,796 women with a minimum of two pregnancies. HPV16-adjusted rate ratios (RR) and confidence intervals were estimated by stratified Cox model. Compared to dual seropositivity already at the first serum sampling, RRs related to HPV6 seropositivity before and after HPV31 seroconversion were 0.4 (95% CI 0.0, 4.4) and 10 (95% CI 1.8, 57). Furthermore, RR related to seroconversions of both HPV18/45 and C.trachomatis between the consecutive pregnancies was 28 (95% CI 4.3, 190). Virtually concomitant HPV18/45 and C.trachomatis infections are associated with very high CIN3 risk. [ABSTRACT FROM AUTHOR]

Background: Investigation of the potential association of single nucleotide polymorphisms (SNPs) at –308 G/A and –238 G/A of Tumor necrosis factor α (TNFα) with susceptibility to HPV-16 associated cervical cancer in Indian women. Methods: The study included 165 histologically confirmed cases with 45 precancer and 120 cancer patients and an equal number (165) of healthy controls with normal cervical cytology. PCR-RFLP was employed to analyze TNFα promoter polymorphisms, which were confirmed by direct sequencing. Both patients and controls were screened for Human Papillomavirus (HPV) infection. Results: The frequency of –308 A allele in TNFα was significantly higher in cases compared with control subjects (21% in cases vs. 9% in controls; p<0.01), with an odds ratio of 2.7 (95% CI = 1.41–5.15). Also, women carrying A allele for this locus presented 3 times increased susceptibility to HPV 16 infection as evident from carrier genotype distribution between HPV positive cases and control subjects (24% in HPV positive cases vs. 9% in controls; p<0.01; OR = 3.1; 95% CI = 1.60–6.03). No such association was found for TNFα–238 (G/A) polymorphism with the risk of development of cervical cancer. Conclusion: It suggests that SNP at –308 (G/A) of TNFα promoter may represent an increased risk for HPV infection and development of cervical cancer in Indian women. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare the depth of necrosis achieved using CO2- and N2O-cryotherapy. Method: We treated 20 women with CO2-cryotherapy and 20 with N2O-cryotherapy 24 h prior to undergoing total hysterectomy for reasons unrelated to cervical cancer. Depth of necrosis in the ectocervix was measured on surgically removed tissue. Results: The mean depth of necrosis for the anterior lip achieved by N2O-cryotherapy was 5.3 mm compared with 3.4 mm by CO2-cryotherapy (P <0.001). We found similar results for the posterior lip (5.0 vs 3.1 mm; P <0.001). N2O-cryotherapy was more likely than CO2-cryotherapy to achieve a depth of necrosis of ≥4.8 mm for the anterior lip (75% vs 15%; P <0.001) and posterior lip (60% vs 5%; P <0.001). Conclusions: Our study showed that CO2-cryotherapy may not achieve the depth of necrosis necessary to completely destroy cervical precancer and therefore may be less robust than N2O-cryotherapy. [Copyright &y& Elsevier]