Tissue-preserving treatment with non-invasive physical plasma of cervical intraepithelial neoplasia-a prospective controlled clinical trial.
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ABSTRACT:
SUBMITTER: Weiss M
PROVIDER: S-EPMC10465690 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
Tissue-preserving treatment with non-invasive physical plasma of cervical intraepithelial neoplasia-a prospective controlled clinical trial.
Weiss Martin M Arnholdt Marcel M Hißnauer Anna A Fischer Irma I Schönfisch Birgitt B Andress Jürgen J Gerstner Sophia S Dannehl Dominik D Bösmüller Hans H Staebler Annette A Brucker Sara Y SY Henes Melanie M
Frontiers in medicine 20230815
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Project description:(1) Background: Cervical intraepithelial neoplasia (CIN) of long-term persistence or associated with individual treatment indications often requires highly invasive treatments. These are associated with risks of bleeding, infertility, and pregnancy complications. For low- and middle-income countries (LMICs), standard treatment procedures are difficult to implement and manage. We characterized the application of the highly energized gas "noninvasive physical plasma" (NIPP) for tissue devitalization and the treatment of CIN. (2) Methods: We report the establishment of a promising tissue devitalization procedure by NIPP application. The procedure was characterized at the in vitro, ex vivo and in vivo levels. We performed the first prospective, single-armed phase-IIb trial in 20 CIN1/2 patients (NCT03218436). (3) Results: NIPP-treated cervical cancer cells used as dysplastic in vitro model exhibited significant cell growth retardation due to DNA damage, cell cycle arrest and apoptosis. Ex vivo and in vivo tissue assessments showed a highly noninvasive and tissue-preserving treatment procedure which induces transmucosal tissue devitalization. Twenty participants were treated with NIPP and attended a 24-week follow-up. Treatment success was achieved in 19 (95%) participants without postinterventional complications other than mild to moderate discomfort during application. (4) Conclusions: The results from this study preliminarily suggest that NIPP could be used for an effective and tissue-preserving treatment for CIN without the disadvantages of standard treatments. However, randomized controlled trials must confirm the efficacy and noninferiority of NIPP compared to standard treatments.
| S-EPMC9027888 | biostudies-literature
Project description:Epidemiologic studies indicate that elevated levels of gamma-glutamyltransferase (GGT), a key enzyme of glutathione metabolism, might be associated with increased cancer risk. Furthermore, preclinical studies support a role for GGT in tumor invasion and progression. However, the relationship between GGT and risks of cervical intraepithelial neoplasia III (CIN-III) and invasive cervical cancer (ICC) have not been evaluated. We investigated the association of enzymatically determined GGT in blood serum with subsequent incidence of CIN-III and ICC in a prospective population-based cohort of 92,843 women ages 18 to 95, of whom 79% had at least one gynecologic examination including Pap smear testing during follow-up. Cox regression was used to compute adjusted hazard ratios (HR) with 95% confidence intervals for the association of GGT with CIN-III and ICC. During median follow-up of 13.8 years, 702 CIN-III and 117 ICC diagnoses were observed. Compared with normal low GGT (<17.99 units/L), risk of ICC was significantly elevated for all other baseline GGT categories, with adjusted HRs of 2.31 (1.49-3.59) for normal high GGT (18.00-35.99 units/L), 2.76 (1.52-5.02) for elevated GGT (36.00-71.99 units/L), and 3.38 (1.63-7.00) for highly elevated GGT [>72.00 units/L; P trend < 0.0001, HR log unit increase 3.45 (1.92-6.19)]. In contrast, associations between GGT serum levels and CIN-III risk were not statistically significant in the main analysis. Exclusion of the first 2 or 5 years of follow-up did not change the results. Effects did not differ by age, body mass index, or socioeconomic status. Our findings implicate GGT in the progression of premalignant cervical lesions to invasive cancer.
| S-EPMC5911687 | biostudies-literature
Project description:BackgroundTreatments for cervical intraepithelial neoplasia remove precancerous cells from the cervix by excising or ablating the transformation zone. Most studies show no association between cervical intraepithelial neoplasia treatments and fertility outcomes. However, only 2 studies have examined time to pregnancy, both using retrospective study designs, with 1 study showing no association and the other showing a 2-fold increased risk of infertility (time to pregnancy >12 months) following excisional or ablative treatment.ObjectiveWe examined the association between cervical intraepithelial neoplasia treatments and fecundability.Materials and methodsWe analyzed data from Pregnancy Study Online (PRESTO), a prospective cohort study of North American pregnancy planners enrolled during 2013-2019. At baseline, women reported whether they ever had an abnormal Papanicolaou test result, the number of abnormal Papanicolaou test results, and their age at first abnormal Papanicolaou test result. They also reported whether they underwent diagnostic (colposcopy) or treatment (excisional or ablative) procedures, and their age at each procedure. We restricted analyses to 8017 women with 6 or fewer cycles of attempt time at enrollment who reported receiving a Papanicolaou test in the previous 3 years. We estimated fecundability ratios and 95% confidence intervals using proportional probabilities models adjusted for sociodemographics, healthcare use, smoking, number of sexual partners, history of sexually transmitted infections, and human papillomavirus vaccination.ResultsA history of abnormal Papanicolaou test results showed little association with fecundability (fecundability ratio, 1.00; 95% confidence interval, 0.95-1.06). Likewise, receipt of colposcopy or treatment procedures, and time since treatment were not materially associated with fecundability. Results were similar when stratified by age and smoking status.ConclusionWe observed no appreciable association of self-reported history of abnormal Papanicolaou test results, colposcopy, treatments for cervical intraepithelial neoplasia, or recency of treatment with fecundability. These results agree with the majority of previous studies in indicating little effect of cervical intraepithelial neoplasia treatments on future fertility.
| S-EPMC8041134 | biostudies-literature
Project description:OBJECTIVE: We investigated whether obesity, physical activity, and calorie intake are associated with the risks of cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: We enrolled 1125 women (age, 18-65 years) into a human papillomavirus cohort study established from 2006 to 2012. Multinomial logistic regression models were used to estimate crude and multivariate odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs), and to assess whether body mass index (BMI), height, weight, total calorie intake, and physical activity were associated with the risks of CIN and cervical cancer. RESULTS: Cervical cancer risk was positively associated with BMI and inversely associated with physical activity. When compared with women with a normal BMI (18.5-23 kg/m(2)), the multivariate ORs (95% CIs) for those overweight (23-25 kg/m(2)) and mild obesity (≥25 kg/m(2)) were 1.25 (0.79-2.00) and 1.70 (1.10-2.63), respectively. When compared with women with the lowest tertile of physical activity (<38.5 MET-hours/week), the ORs (95% CIs) for cervical cancer were 0.95 (0.61-1.48) and 0.61 (0.38-0.98) for women with medium physical activity (38.5-71.9 MET-hours/week) and those with high physical activity (72 MET-hours/week), respectively (p for linear trend = 0.03). The CIN2/3 risk was inversely associated with physical activity after adjustment for confounders. Compared with women with low physical activity (< 38.5 MET-hours/week), the ORs (95% CIs) for CIN2/3 were 0.64 (0.40-1.01) and 0.58 (0.36-0.93) for the medium and high physical activity groups, respectively (p for linear trend = 0.02). Total calorie intake was not statistically associated with the risks of CIN and cervical cancer after adjustment for confounders. CONCLUSION: Our results indicate that in addition to screening for and treatment of CIN, recommendations on the maintenance of an appropriate BMI with an emphasis on physical activity could be an important preventive strategy against the development of cervical cancer.
| S-EPMC3680419 | biostudies-other
Project description:Cervical intraepithelial neoplasia (CIN) is a precancerous condition inducing local lesions on the surface of the squamocolumnar junction of the cervix. Despite the role of vaginal microbiota having been under-discussed, the role of the cervical microbiome and the microbial migration across the reproductive tract involved in CIN was limitedly studied. We aimed to synchronously characterize the dysbiosis associated with CIN in both the cervix and vagina in a Chinese population. Profiling of cervical and vaginal microbiota from 60 CIN women and 60 healthy women was conducted. 16S rRNA sequencing was adopted. By comparing the microbial profiles between different parts of the reproductive tract, our results demonstrated an increased shift of microbial diversity in the cervix compared with that in the vagina for the CIN patients, specifically in CIN 1. Less dysbiosis was found between the CIN patients and controls, in either the vagina or cervix. The microbial community may be modulated by the onset of sexual activity, a known clinical risk factor for cervical neoplasia. Distinct patterns of perturbated bacteria were found in the vaginal and cervical microbiota, in which reduced Actinobacteria-related operational taxonomic units (OTUs) and increased Proteobacteria-related OTUs were found in the vagina and cervix, respectively. A good agreement between the direction of the top-significant perturbated OTUs was observed between the vaginal and cervical microbiome, suggesting a potential microbial migration in the reproductive tract. Enriched genera such as Sphingomonas and Stenotrophomonas were found in cervical microbiota-associated CIN. Multivariate analysis revealed Comamonas, Rhizobium, and Pseudomonas as independent genera contributing to CIN in the cervix. In summary, this study revealed the perturbation of microbiota in the presence of CIN and demonstrated a distinct pattern of characteristic bacteria community between the vagina and cervix involved in the development of CIN.
| S-EPMC8885166 | biostudies-literature
Project description:Cervical cancer is one of the leading causes of cancer-related deaths among women and it is caused by the human papillomavirus (HPV). High variation has been reported in the attribution of specific HPV genotypes to cervical neoplasia among various geographic regions. For effective control of cervical cancer through HPV vaccination, it is essential to estimate the cost-effectiveness of vaccination, to monitor the potential transition into other HPV genotypes, and to understand the distribution of specific HPV genotypes across a specific geographic region. In this study, the distribution of HPV genotypes was investigated in southeast China, from 2011 to 2016. The 12,816 cervical swabs collected from women (age 18-78 years, median 43.6 years) outpatients were analyzed. HPV prevalence among 12,816 cervical swabs analyzed was 22.3% (2,856/12,816). Among these positive cases, 2,216 had only one HPV genotype while 640 had multiple HPV genotypes. The cases with multiple types revealed 23 different HPV genotypes with the five most prevalent being HPV18 (18.2%), HPV52 (14.1%), HPV16 (11.9%), HPV58 (10.6%), and HPV33 (5.5%). The rates of HPV infection in patients with cervical inflammation, CIN-1, CIN-2, CIN-3, squamous carcinoma, and adenocarcinoma were 38.4%, 80.5%, 82.6%, 92.3%, 97.5%, and 93.4%, respectively. Four HPV genotypes, HPV18, HPV16, HPV52, and HPV58, were more prevalent in patients with CIN-2-CIN-3 and invasive cervical cancer. A comparison of HPV genotypes attribution to cervical cancer between southeast China and global incidences revealed distinct differences. Due to this unique prevalence, it is essential to streamline the vaccination development protocol prior to administering vaccines based on global data.
| S-EPMC6196990 | biostudies-literature
Project description:BackgroundCervical screening is transitioning from primary cytology to primary human papillomavirus (HPV) testing. HPV testing is highly sensitive but there is currently no high-specificity triage method for colposcopy referral to detect cervical intraepithelial neoplasia grade 3 or above (CIN3+) in women positive for high-risk (hr) HPV subtypes. An objective, automatable test that could accurately perform triage, independently of sample heterogeneity and age, is urgently required.MethodsWe analyzed DNA methylation at ~850,000 CpG sites across the genome in a total of 1254 cervical liquid-based cytology (LBC) samples from cases of screen-detected histologically verified CIN1-3+ (98% hrHPV-positive) and population-based control women free from any cervical disease (100% hrHPV-positive). Samples were provided by a state-of-the-art population-based cohort biobank and consisted of (i) a discovery set of 170 CIN3+ cases and 202 hrHPV-positive/cytology-negative controls; (ii) a diagnostic validation set of 87 CIN3+, 90 CIN2, 166 CIN1, and 111 hrHPV-positive/cytology-negative controls; and (iii) a predictive validation set of 428 cytology-negative samples (418 hrHPV-positive) of which 210 were diagnosed with CIN3+ in the upcoming 1-4 years and 218 remained disease-free.ResultsWe developed the WID-CIN (Women's cancer risk IDentification-Cervical Intraepithelial Neoplasia) test, a DNA methylation signature consisting of 5000 CpG sites. The receiver operating characteristic area under the curve (AUC) in the independent diagnostic validation set was 0.92 (95% CI 0.88-0.96). At 75% specificity (≤CIN1), the overall sensitivity to detect CIN3+ is 89.7% (83.3-96.1) in all and 92.7% (85.9-99.6) and 65.6% (49.2-82.1) in women aged ≥30 and <30. In hrHPV-positive/cytology-negative samples in the predictive validation set, the WID-CIN detected 54.8% (48.0-61.5) cases developing 1-4 years after sample donation in all ages or 56.9% (47.6-66.2) and 53.5% (43.7-63.2) in ≥30 and <30-year-old women, at a specificity of 75%.ConclusionsThe WID-CIN test identifies the vast majority of hrHPV-positive women with current CIN3+ lesions. In the absence of cytologic abnormalities, a positive WID-CIN test result is likely to indicate a significantly increased risk of developing CIN3+ in the near future.
| S-EPMC9580141 | biostudies-literature
Project description:RAP1 (RAS proximate 1), a small GTP-binding protein of the RAS superfamily, is a putative oncogene that is highly expressed in several malignant cell lines and types of cancers, including some types of squamous cell carcinoma. However, the participation of RAP1 in cervical carcinogenesis is unknown. We conducted a cross-sectional study of paraffin-embedded cervical biopsies to determine the association of RAP1 with cervical intraepithelial neoplasia (CIN). Standard and quantitative immunohistochemistry assessment of RAP1 expression in fixed tissue was performed on 183 paraffin-embedded cervical biopsies that were classified as normal or non-dysplastic mucosa (NDM) (n = 33); CIN grade 1 (n = 84) and CIN grade 2/3 (n = 66). A gradual increase in RAP1 expression in NDM < CIN 1 < CIN 2/3 (p<0.001) specimens was observed and was in agreement with the histopathologic diagnosis. A progressive increase in the RAP1 expression levels increased the risk of CIN 1 [odds ratio (OR) = 3.50; 95% confidence interval (CI) 1.30-10.64] 3.5 fold and the risk of CIN 2/3 (OR = 19.86, 95% CI 6.40-70.79) nearly 20 fold when compared to NDM. In addition, stereotype ordinal regression analysis showed that this progressive increase in RAP1 expression more strongly impacted CIN 2/3 than CIN 1. Our findings suggest that RAP1 may be a useful biomarker for the diagnosis of CIN.
| S-EPMC4391937 | biostudies-literature
Project description:ObjectiveHypermethylation of human papillomavirus (HPV) and host genes has been reported in cervical cancer. However, the degree of methylation of different HPV types relative to the severity of the cervical lesions remains controversial. Studies of the degree of methylation associated with the host gene and the HPV genome to the severity of cervical lesions are rare. We examined the association of methylation status between host genes and late gene 1 (L1) regions of HPV16, 18, 52, and 58 in cervical brushings.MethodsCervical brushings from 147 HPV-infected patients were obtained. The samples comprised normal (n=28), cervical intraepithelial neoplasia (CIN) 1 (n=45), CIN2 (n=13), and CIN3/carcinoma in situ (n=61). The methylation status of HPV and host genes was measured using bisulfite pyrosequencing and quantitative methylation-specific polymerase chain reaction (PCR).ResultsThe degree of methylation of L1 in HPV16, 18, and 52 was associated with the severity of the cervical lesion. In HPV52, C-phosphate-G (CpG) sites 6368m, 6405m, and 6443m showed significantly higher methylation in lesions ≥CIN3 (p=0.005, 0.003, and 0.026, respectively). Methylation of most HPV types except HPV52 (r<-0.1) was positively correlated with the degree of methylation of host genes including PAX1 and SOX1 (0.4≤r≤0.7). Combining HPV methylation with PAX1 methylation improved the clustering for ≥CIN2.ConclusionOur study showed that the degree of L1 methylation of HPV16, 18, and 52 but not 58 is associated with the severity of cervical lesions. The association between HPV methylation and host gene methylation suggests different responses of host cellular epigenetic machinery to different HPV genotypes.
| S-EPMC5447154 | biostudies-literature
Project description:Identification of promoter methylation profile associated with cervical cancer progression. The Ilumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs from 19 cervical samples (including normal, CIN I-II, in situ and invasive cervical cancer tissues).
2013-01-01 | GSE41384 | GEO