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Imiquimod for Cervical and Vaginal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis.Obstetrics and Gynecology Aug 2023To evaluate the treatment efficacy and the risk of adverse events of imiquimod for cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VAIN),... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the treatment efficacy and the risk of adverse events of imiquimod for cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VAIN), compared with placebo or no intervention.
DATA SOURCES
We searched Cochrane, PubMed, ISRCTN registry, ClinicalTrials.gov , and the World Health Organization International Clinical Trials Registry Platform up to November 23, 2022.
METHODS OF STUDY SELECTION
We included randomized controlled trials and prospective nonrandomized studies with control arms that investigated the efficacy of imiquimod for histologically confirmed CIN or VAIN. The primary outcomes were histologic regression of the disease (primary efficacy outcome) and treatment discontinuation due to side effects (primary safety outcome). We estimated pooled odds ratios (ORs) of imiquimod, compared with placebo or no intervention. We also conducted a meta-analysis of the proportions of patients with adverse events in the imiquimod arms.
TABULATION, INTEGRATION, AND RESULTS
Four studies contributed to the pooled OR for the primary efficacy outcome. An additional four studies were available for meta-analyses of proportions in the imiquimod arm. Imiquimod was associated with increased probability of regression (pooled OR 4.05, 95% CI 2.08-7.89). Pooled OR for CIN in the three studies was 4.27 (95% CI 2.11-8.66); results of one study were available for VAIN (OR, 2.67, 95% CI 0.36-19.71). Pooled probability for primary safety outcome in the imiquimod arm was 0.07 (95% CI 0.03-0.14). The pooled probabilities (95% CI) of secondary outcomes were 0.51 (0.20-0.81) for fever, 0.53 (0.31-0.73) for arthralgia or myalgia, 0.31 (0.18-0.47) for abdominal pain, 0.28 (0.09-0.61) for abnormal vaginal discharge or genital bleeding, 0.48 (0.16-0.82) for vulvovaginal pain, and 0.02 (0.01-0.06) for vaginal ulceration.
CONCLUSION
Imiquimod was found to be effective for CIN, whereas data on VAIN were limited. Although local and systemic complications are common, treatment discontinuation is infrequent. Thus, imiquimod is potentially an alternative therapy to surgery for CIN.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42022377982.
Topics: Female; Humans; Imiquimod; Antineoplastic Agents; Prospective Studies; Aminoquinolines; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms
PubMed: 37411024
DOI: 10.1097/AOG.0000000000005256 -
Pathology, Research and Practice Aug 2023Management of oral potentially malignant disorders (OPMDs) is still challenging. Despite the diagnostic ascertainment by bioptic examination, this method is poorly... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Management of oral potentially malignant disorders (OPMDs) is still challenging. Despite the diagnostic ascertainment by bioptic examination, this method is poorly informative of the prognosis and subsequent malignant transformation. Prognosis is based on histological findings by grading of dysplasia. Immunohistochemical expression of p16 has been investigated in different studies, with controversial results. In this scenario, we systematically revised the current evidence about p16 immunohistochemical expression and the risk of malignization of OPMDs.
MATERIAL AND METHODS
After a proper set of keywords combination, 5 databases were accessed and screened to select eligible studies. The protocol was previously registered on PROSPERO (Protocol ID: CRD42022355931). Data were obtained directly from the primary studies as a measure to determine the relationship between CDKN2A/P16 expression and the malignant transformation of OPMDs. Heterogeneity and publication bias were investigated by different tools, such as Cochran's Q test, Galbraith plot and Egger and Begg Mazumdar's rank tests.
RESULTS
Meta-analysis revealed a twofold increased risk to malignant development (RR = 2.01, 95% CI = 1.36-2.96 - I = 0%). Subgroup analysis did not highlight any relevant heterogeneity. Galbraith plot showed that no individual study could be considered as an important outlier.
CONCLUSION
Pooled analysis showed that p16 assessment may arise adjunct tool to dysplasia grading, leading to an optimized determination of the potential progression to cancer of OPMDs. The p16 overexpression analysis by immunohistochemistry techniques has a multitude of virtues that may facilitate its incorporation in the day-to-day prognostic study of OPMDs.
Topics: Humans; Cyclin-Dependent Kinase Inhibitor p16; Biomarkers, Tumor; Prognosis; Precancerous Conditions; Mouth Neoplasms
PubMed: 37406376
DOI: 10.1016/j.prp.2023.154656 -
Current Oncology (Toronto, Ont.) Jun 2023This guideline provides evidence-based guidance on the risk-based management of cervical dysplasia in the colposcopy setting in the context of primary HPV-based...
This guideline provides evidence-based guidance on the risk-based management of cervical dysplasia in the colposcopy setting in the context of primary HPV-based screening and HPV testing in colposcopy. Colposcopy management of special populations is also discussed. The guideline was developed by a working group in collaboration with the Gynecologic Oncology Society of Canada (GOC), Society of Colposcopists of Canada (SCC) and the Canadian Partnership Against Cancer (CPAC). The literature informing these guidelines was obtained through a systematic review of the relevant literature via a multi-step search process led by information specialists. The literature was reviewed up to June 2021 with manual searches of relevant national guidelines and more recent publications. Quality of the evidence and strength of recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The intended users of this guideline include gynecologists, colposcopists, screening programs and healthcare facilities. Implementation of the recommendations is intended to promote equitable and standardized care for all people undergoing colposcopy in Canada. The risk-based approach aims to improve personalized care and reduce over-/under-treatment in colposcopy.
Topics: Female; Humans; Pregnancy; Colposcopy; Uterine Cervical Neoplasms; Papillomavirus Infections; Canada; Uterine Cervical Dysplasia
PubMed: 37366914
DOI: 10.3390/curroncol30060431 -
Journal of Cancer Research and... 2023Oral malignant and potentially malignant conditions affect several people worldwide each year. The early diagnoses of these conditions play an important role in... (Meta-Analysis)
Meta-Analysis Review
Oral malignant and potentially malignant conditions affect several people worldwide each year. The early diagnoses of these conditions play an important role in prevention and recovery. Vibrational spectroscopy techniques such as Raman spectroscopy (RS) and Fourier-transform infrared (FTIR) spectroscopy are used in the early, non-invasive, label-free diagnosis of malignant and pre-malignant conditions, and are areas of active research. However, there is no conclusive evidence suggesting the translatability of these methods into clinical practice. This systematic review and meta-analysis presents pooled evidence for RS and FTIR methods in the detection of malignant and potentially malignant conditions of the oral cavity. Electronic databases were searched for published literature on RS and FTIR in the diagnosis of oral malignant and potentially malignant conditions. The pooled sensitivity, specificity, diagnostic accuracy, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), pre-test, and post-test probability were then calculated using the random-effects model. A subgroup analysis was conducted separately for RS and FTIR methods. A total of 12 studies were included (8 of RS; 4 of FTIR) as per the eligibility criteria. The pooled sensitivity and specificity of the vibrational spectroscopy methods were calculated to be 0.99 (95% confidence interval [CI]: 0.90, 1.00) and 0.94 (95% CI: 0.85, 0.98), respectively. The area under the curve (AUC) for the summary receiving operator characteristic curve was found to be 0.99 (0.98-1.00). Therefore, the results obtained in this study suggest that the RS and FTIR methods offer great potential to be used in the early diagnosis of oral malignant and pre-malignant conditions.
Topics: Humans; Spectrum Analysis, Raman; Area Under Curve; Databases, Factual; Mouth; Odds Ratio; Syndrome
PubMed: 37313896
DOI: 10.4103/jcrt.jcrt_2275_21 -
Journal of International Society of... 2023Oral submucous fibrosis (OSMF) is known to be one of the most common premalignant conditions of the oral cavity. Areca nut (AN) is considered to be the disease's primary... (Review)
Review
AIMS AND OBJECTIVES
Oral submucous fibrosis (OSMF) is known to be one of the most common premalignant conditions of the oral cavity. Areca nut (AN) is considered to be the disease's primary cause, while there are other potential causes as well. However, routine clinical practice has revealed that not all people who chew AN exhibit clinical signs of OSMF, and few people are reported to have it even without chewing AN. So, there must be other factors contributing to OSMF. Plasma fibrinogen degradation products (FDPs) have recently been discovered to be an early sign of this disease, indicating a potential link between the two. This review aims to examine the studies which have been published in the literature that explain the role of plasma FDPs in contributing to OSMF.
MATERIALS AND METHODS
An electronic search of the published literature was performed without publication year limitation in PubMed/ Medline, Scopus, Google Scholar, Web of Science, Science Direct, Embase, and Research gate databases, using mesh keywords like ('Oral submucous fibrosis' OR 'Oral submucous fibrosis') AND ('Fibrinogen degradation products' OR 'Plasma fibrinogen degradation products') AND ('Clinical grades' OR 'Histological grades') AND ('Diagnosis'). A manual search of all related journals was also done. We also referred to the reference lists of papers. The risk of bias was evaluated with the GRADE criteria (from the Grading of Recommendations Assessment, Development, and Evaluation Working Group).
RESULTS
The search revealed a total of 12 relevant studies from 1979 to 2022. Nine out of 12 studies demonstrated the definite presence of plasma FDPs in such cases.
CONCLUSIONS
Although the studies documented in the literature showing evidence of plasma FDPs in patients with OSMF are very few in number, their detection signifies an important clinical finding. More research is still required in this aspect to establish stronger evidence.
PubMed: 37223447
DOI: 10.4103/jispcd.JISPCD_229_22 -
Cancer Medicine Jul 2023The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high-risk individuals and lesions... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high-risk individuals and lesions because these biomarkers are useful in developing personalized management strategies for OL patients. This study systematically searched and analyzed the literature on potential saliva and serum biomarkers for OL malignant transformation.
METHODS
PubMed and Scopus were searched for studies published up to April 2022. The primary outcome of this study was the difference in biomarker concentrations in saliva or serum samples from healthy control (HC), OL and oral cancer (OC) populations. Cohen's d with 95% credible interval was calculated and pooled using the inverse variance heterogeneity method.
RESULTS
A total of seven saliva biomarkers were analyzed in this paper, including interleukin-1alpha, interleukin-6 (IL-6), interleukin-6-8, tumor necrosis factor alpha (TNF-α), copper, zinc, and lactate dehydrogenase. IL-6 and TNF-α exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. A total of 13 serum biomarkers were analyzed, including IL-6, TNF-α, C-reactive protein, total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, albumin, protein, β2-microglobulin, fucose, lipid-bound sialic acid (LSA), and total sialic acid (TSA). LSA and TSA exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC.
CONCLUSION
IL-6 and TNF-α in saliva have strong predictive values for OL deterioration, and LSA and TSA concentration levels in serum also have the potential to serve as biomarkers for OL deterioration.
Topics: Humans; Interleukin-6; Tumor Necrosis Factor-alpha; N-Acetylneuraminic Acid; Leukoplakia, Oral; Biomarkers; Mouth Neoplasms; Cell Transformation, Neoplastic
PubMed: 37199052
DOI: 10.1002/cam4.6095 -
BMC Women's Health May 2023To systematically evaluate several factors of persistent human papillomavirus (HPV) infection following conization in patients with cervical intraepithelial neoplasia... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically evaluate several factors of persistent human papillomavirus (HPV) infection following conization in patients with cervical intraepithelial neoplasia (CIN).
METHODS
PubMed, EMBASE and the Cochrane Library were searched from January 1, 1998 to September 10, 2021. Random-effects models for meta-analyses were used and pooled relative risks with 95% confidence intervals were reported. Literature screening, data extraction, and assessment of the risk of bias in the included studies were conducted independently by two researchers. Data analysis was performed with Stata software, version 12.0.
RESULTS
A total of 28 studies were included in this study. Meta-analysis revealed that surgical margin and residual disease were positively correlated with persistent HPV infection after conization. Compared with patients infected with other types of HPV, CIN patients with HPV 16 had a higher persistent infection rate (OR = 1.967, 95% CI (1.232-3.140), P < 0.05).
CONCLUSIONS
CIN patients who are postmenopausal, have positive surgical margins and residual lesions, and are positive for HPV 16 are prone to persistent HPV infection after conization.
Topics: Conization; Humans; Female; Uterine Cervical Dysplasia; Papillomavirus Infections; Papillomaviridae; Uterine Cervical Neoplasms
PubMed: 37138261
DOI: 10.1186/s12905-023-02360-w -
Medicina Oral, Patologia Oral Y Cirugia... Sep 2023Oral squamous cell carcinoma (OSCC) is gradually increasing its incidence in our society. Unfortunately, this entity is diagnosed at an advanced stage in most patients,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral squamous cell carcinoma (OSCC) is gradually increasing its incidence in our society. Unfortunately, this entity is diagnosed at an advanced stage in most patients, a fact that implies greater difficulty in its treatment and a worse prognosis. This systematic review aims to assess whether the cytokines IL-6, IL-8 and TNF-α are potential salivary biomarkers that allow early diagnosis of cancer.
MATERIAL AND METHODS
An electronic search was performed in three databases (Pubmed, Scopus and Web of Science). We used the following keywords: "salivary cytokines", "saliva cytokines", "salivary interleukins", "biomarkers", "oral squamous cell carcinoma" and "diagnosis", combined with the Boolean operators "AND" and "OR".
RESULTS
128 publications were found and finally 23 articles were included in the review and 15 in the meta-analysis. It has been observed that the majority of OSCC patients express higher salivary concentrations of IL-6, IL-8 and TNF-α compared to the control (CL) and premalignant lesion (OPML) groups. It has also been observed that the different premalignant lesions do not have statistically significant differences in the salivary concentration of the cytokines, and on the other hand, differences have been observed between the different TNM stages. The meta-analysis has shown that the difference in concentration of IL-6, IL-8 and TNF-α is statistically significant between the CL group and the OSCC, and also between the CL group and OPML.
CONCLUSIONS
There is sufficient evidence to affirm that IL-6, IL-8 and TNF-α are useful salivary cytokines in the early diagnosis and prognosis of OSCC. Although future studies are necessary to establish greater reliability of these biomarkers and thus be able to develop a valid diagnostic test.
Topics: Humans; Cytokines; Tumor Necrosis Factor-alpha; Interleukin-6; Interleukin-8; Reproducibility of Results; Biomarkers, Tumor; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Mouth Neoplasms; Prognosis; Head and Neck Neoplasms; Saliva
PubMed: 37099710
DOI: 10.4317/medoral.25889 -
PloS One 2023Chronic atrophic gastritis is a significant premalignant lesion of gastric carcinoma. There is a great need to prevent the progression to gastric carcinoma through early... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic atrophic gastritis is a significant premalignant lesion of gastric carcinoma. There is a great need to prevent the progression to gastric carcinoma through early intervention and treatment for chronic atrophic gastritis. Weifuchun, a famous Chinese patent drug, has been widely used for chronic atrophic gastritis in China. However, it remains unclear whether Weifuchun is effective for atrophic gastritis.
OBJECTIVE
To determine the effectiveness and safety of Weifuchun for chronic atrophic gastritis.
METHODS
We systematically retrieved seven databases (Cochrane Library, EMBASE, PubMed, China National Knowledge Infrastructure, Wanfang database, Chinese Scientific Journals Database, and Chinese Biological Medical Database) from their inception to October 5, 2022. Methodological quality was examined using the Cochrane Risk of bias tool. We also used RevMan 5.4 software for statistical analysis to examine the effectiveness and safety of Weifuchun.
RESULTS
Fifteen studies with 1,488 patients were enrolled in this meta-analysis. The study indicated that Weifuchun was more effective (RR 1.52; 95% CI 1.41, 1.63; p<0.00001) than Western medicine and other Chinese patent medicine. In addition, Weifuchun was more effective in improving gastric mucosal under gastroscopy, improving histopathologic changes of gastric mucosal, and inhibiting Helicobacter pylori. However, no significant difference in safety was examined between Weifuchun and the control group (RR 2.83; 95% CI 0.85, 9.38; P = 0.09).
CONCLUSIONS
The meta-analysis revealed a significant statistical difference with Weifuchun in effectiveness compared to the control group. However, there was no significant difference in safety. Thus, more high-quality clinical studies are needed in the future.
TRIAL REGISTRATION
Registration number CRD42022365703.
Topics: Humans; Gastritis, Atrophic; Drugs, Chinese Herbal; Tablets; Carcinoma
PubMed: 37053262
DOI: 10.1371/journal.pone.0284411 -
International Journal of Molecular... Mar 2023Cervical intraepithelial neoplasia grade 2 (CIN2) is an intermediate stage between CIN 1, which is a low-grade lesion, and CIN3, which is the immediate precursor of... (Review)
Review
Cervical intraepithelial neoplasia grade 2 (CIN2) is an intermediate stage between CIN 1, which is a low-grade lesion, and CIN3, which is the immediate precursor of cervical cancer (CC). Traditionally, CIN2 was regarded as a high-grade lesion and was treated with conization or ablative methods. In recent years, there has been a shift in the management of younger patients, who are now more often being managed conservatively due to frequent spontaneous CIN2 regression and possible adverse effects of treatment on future pregnancies. Because the risk of progression to CC still exists with conservative management, a personalized approach is needed to identify patients with a higher probability of progression. In this regard, research has focused on the role of host and human papillomavirus (HPV) gene methylation. This systematic review summarizes the current knowledge regarding conservative CIN2 management focusing on the main methylation markers and its implementation in conservative CIN2 management, and it describes major ongoing longitudinal studies on the subject. The review showed that DNA methylation is an accurate predictor of disease progression and a valid triage tool for HPV-positive women, with CIN2 performing better than triage cytology. Because virtually all CCs are methylation-positive, methylation-negative women at baseline have an extremely low risk of CC.
Topics: Pregnancy; Humans; Female; Human Papillomavirus Viruses; Papillomavirus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; DNA Methylation; DNA; Papillomaviridae
PubMed: 37047452
DOI: 10.3390/ijms24076479