Accuracy of mRNA HPV Tests for Triage of Precursor Lesions and Cervical Cancer: A Systematic Review and Meta-Analysis

Macedo, Ana; Gonçalves, João Carlos N; Bavaresco, Daniela V.; Grande, Antônio José; Silva, Napoleão Chiaramonte; Rosa, Maria Inês da

doi:10.1155/2019/6935030

Cited by 13 publications

(12 citation statements)

References 72 publications

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“…Similarly, a smaller area under receiver operating characteristic curve (AUC) of 0.59 was reported by Ren et al [29], compared to 0.80 reported by Camus et al [37], of which the disparity might have resulted from a difference in the type of included study participants who had different cervical pathologies. Although our findings are in agreement with a similar review by Macedo et al, which recorded pooled sensitivity, specificity and AUC of 92.8, 60.5% and 0.88, respectively, [56], more robust clinical translation studies using larger consecutive cohorts of women participants is recommended for adequate validation.…”

Section: Discussionsupporting

confidence: 92%

“…The proportion of CIN2+ varied between 13.7 and 88.4%, reflecting the diverse spectrum of cervical pathologies of the participants employed in articles we included. From experimental studies, it has been established that woman exposed to HPV E6/E7 mRNA following infection with HPV have higher risk of progressing to highgrade cervical neoplasia due to the integration of viral DNA sequence into host genome causing loss of E2 tumor suppressor gene that regulates expression of E6 and E7 oncogenes [13,54,56]. Consequently, this results in overexpression of the two oncogenes which become useful in evaluating risk of cervical carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review

Onyango

Ogonda

Guyah

et al. 2020

Infect Agents Cancer

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Background Cervical cancer screening is slowly transitioning from Pappanicolaou cytologic screening to primary Visual Inspection with Acetic Acid (VIA) or HPV testing as an effort to enhance early detection and treatment. However, an effective triage tests needed to decide who among the VIA or HPV positive women should receive further diagnostic evaluation to avoid unnecessary colposcopy referrals is still lacking. Evidence from experimental studies have shown potential usefulness of Squamous Cell Carcinoma Antigen (SCC Ag), Macrophage Colony Stimulating Factor (M-CSF), Vascular Endothelial Growth Factor (VEGF), MicroRNA, p16INKa / ki-67, HPV E6/E7/mRNA, and DNA methylation biomarkers in detecting premalignant cervical neoplasia. Given the variation in performance, and scanty review studies in this field, this systematic review described the diagnostic performance of some selected assays to detect high-grade cervical intraepithelial neoplasia (CIN2+) with histology as gold standard. Methods We systematically searched articles published in English between 2012 and 2020 using key words from PubMed/Medline and SCOPUS with two reviewers assessing study eligibility, and risk of bias. We performed a descriptive presentation of the performance of each of the selected assays for the detection of CIN2 + . Results Out of 298 citations retrieved, 58 articles were included. Participants with cervical histology yielded CIN2+ proportion range of 13.7–88.4%. The diagnostic performance of the assays to detect CIN2+ was; 1) SCC-Ag: range sensitivity of 78.6–81.2%, specificity 74–100%. 2) M-CSF: sensitivity of 68–87.7%, specificity 64.7–94% 3) VEGF: sensitivity of 56–83.5%, specificity 74.6–96%. 4) MicroRNA: sensitivity of 52.9–67.3%, specificity 76.4–94.4%. 5) p16INKa / ki-67: sensitivity of 50–100%, specificity 39–90.4%. 6) HPV E6/E7/mRNA: sensitivity of 65–100%, specificity 42.7–90.2%, and 7) DNA methylation: sensitivity of 59.7–92.9%, specificity 67–98%. Conclusion Overall, the reported test performance and the receiving operating characteristics curves implies that implementation of p16ink4a/ki-67 assay as a triage for HPV positive women to be used at one visit with subsequent cryotherapy treatment is feasible. For the rest of assays, more robust clinical translation studies with larger consecutive cohorts of women participants is recommended.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review

Onyango

Ogonda

Guyah

et al. 2020

Infect Agents Cancer

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“…In addition, the diagnostic metaanalyses of miRNAs for CIN or CC also were scarce. Similarly, most of meta-analyses focused on the diagnostic value of the HPV DNA testing [33][34][35], cytology [36][37][38], or combination of HPV DNA testing and cytology [39,40] for CIN or CC patients. Therefore, we conducted this meta-analysis, aimed at evaluating the diagnostic efficacy of miRNAs for CIN and CC patients, which might provide some useful information for clinician about early identification of CIN or CC.…”

Section: Introductionmentioning

confidence: 99%

Identification of Circulating MicroRNAs as a Promising Diagnostic Biomarker for Cervical Intraepithelial Neoplasia and Early Cancer: A Meta‐Analysis

Jiang

Hu²,

Zuo

et al. 2020

BioMed Research International

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Background. Cervical cancer (CC) is one of the most common female malignant tumors. And cervical intraepithelial neoplasia (CIN) is the precancerous lesion of CC, which can progress to invasive CC. MicroRNAs (miRNAs) have been found to be potential diagnostic biomarkers for CIN or CC. However, recently, the lack of sufficient studies about the diagnostic value of miRNAs for CIN made it challenging to separately investigate the diagnostic efficacy of miRNAs for CIN. Likewise, the conclusions among those studies were discordant. Therefore, we conducted this meta-analysis, aimed at evaluating the diagnostic efficacy of miRNAs for CIN and CC patients. Methods. Literature search was performed in PubMed, Embase, and Web of Science databases. Pooled sensitivity, specificity, and other diagnostic parameters were calculated through Stata 14.0 software. Furthermore, subgroup analyses and metaregression analysis were conducted to explore the main sources of heterogeneity. Results. Ten articles covering 50 studies were eligible, which included 5,908 patients and 4,819 healthy individuals. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.81 (95% CI, 0.77-0.85), 0.86 (95% CI, 0.83-0.89), 5.9 (95% CI, 4.5-7.7), 0.22 (95% CI, 0.17-0.28), 27 (95% CI, 17-44), and 0.91 (95% CI, 0.88-0.93), respectively. Additionally, the ethnicity and internal reference were the main sources of heterogeneity. Conclusions. Circulating miRNAs can be a promising noninvasive diagnostic biomarker for CIN and early CC, especially miR-9 and miR-205, which need to be verified by large-scale studies.

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“…Furthermore, Fontecha et al claim that the mRNA test combined with cytology has more clinical relevance than hrHPV DNA screening in women with low-grade lesions [75]. Similarly, in a recent meta-analysis by Macedo et alit was reported that E6/E7 mRNA has a sensitivity of 93.9% and a specificity of 61.7% for CIN2+ lesions [82].…”

Section: Hrhpv Transcriptional Statusmentioning

confidence: 98%

Cervical cancer risk profiling: molecular biomarkers predicting the outcome of hrHPV infection

Molina

Diatricch

Quintana

et al. 2020

Expert Review of Molecular Diagnostics

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Introduction: Cervical cancer affects half a million women worldwide annually. Given the association between high-risk human papillomavirus (hrHPV) infection and carcinogenesis, hrHPV DNA testing became an essential diagnostic tool. However, hrHPV alone does not cause the disease, and, most importantly, many cervical lesions regress to normal in a year because of the host immune system. Hence, the low specificity of hrHPV DNA tests and their inability to predict the outcome of infections have triggered a further search for biomarkers. Areas covered: We evaluated the latest viral and cellular biomarkers validated for clinical use as primary screening or triage for cervical cancer and assessed their promise for prevention as well as potential use in the future. The literature search focused on effective biomarkers for different stages of the disease, aiming to determine their significance in predicting the outcome of hrHPV infections. Expert opinion: Biomarkers such as p16/Ki-67, hrHPV genotyping, hrHPV transcriptional status, and methylation patterns have demonstrated promising results. Their eventual implementation in the screening programs may support the prompt diagnosis of hrHPV infection and its progression to cancer. These biomarkers will help in making clinical management decisions on time, thus, saving the lives of hrHPV-infected women, particularly in developing countries.

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Accuracy of mRNA HPV Tests for Triage of Precursor Lesions and Cervical Cancer: A Systematic Review and Meta-Analysis

Cited by 13 publications

References 72 publications

Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review

Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review

Identification of Circulating MicroRNAs as a Promising Diagnostic Biomarker for Cervical Intraepithelial Neoplasia and Early Cancer: A Meta‐Analysis

Cervical cancer risk profiling: molecular biomarkers predicting the outcome of hrHPV infection

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