p16/ki67 and E6/E7 mRNA Accuracy and Prognostic Value in Triaging HPV DNA-Positive Women

Rossi, Paolo Giorgi; Carozzi, Francesca; Ronco, Guglielmo; Allìa, Elena; Bisanzi, Simonetta; Gillio‐Tos, Anna; Marco, Laura De; Rizzolo, Raffaella; Gustinucci, Daniela; Mistro, Annarosa Del; Frayle, Helena; Confortini, Massimo; Iossa, Anna; Cesarini, Elena Nardi; Bulletti, Simonetta; Passamonti, Basilio; Gori, Silvia; Toniolo, Laura; Barca, Alessandra; Bonvicini, Laura; Mancuso, Pamela; Venturelli, Francesco; Benevolo, Maria

doi:10.1093/jnci/djaa105

Cited by 50 publications

(54 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our study results are essentially consistent with the data from other reports on the evaluation of the diagnostic performance of p16/Ki67 dual-stained cytology for triaging HPV-positive cases [15,20,21,24]. All comparator studies involved groups of women <30 years, and most of them included women aged 21-24, as was designed in our investigation.…”

Section: Discussionsupporting

confidence: 91%

“…Similarities with several studies in the sensitivity levels for detection HSIL (CIN2+) obtained in our screening model 1 were noted, including the study of the New Technologies for Cervical Cancer Screening group [24] (81.8%), the report of the Wentzensen et al [20] (86.8%) in a comparable to our size study and the ATHENA sub-study trial-similarities with our results were observed only in the group with p16/Ki67 triaging N16/N18 HPVpositive test results (82.8%) [15]. A difference was found with the ATHENA study in the specificity for HSIL (CIN2+) detection (75.6% reported in the ATHENA).…”

Section: Discussionsupporting

confidence: 87%

See 1 more Smart Citation

Is Primary HPV with Secondary p16/Ki67 Dual-Stain an Alternative HSIL-Risk Detection Strategy in Cervical Cancer Screening for Women under 30 Years?

et al. 2021

View full text Add to dashboard Cite

Recently, cervical cancer rates elevation has been noted in women aged 20–39 years in regions with a very high human development index (HDI). The onset of cancer elevation rates is observed in the age range of 25–29 years, which should necessitate effective precancer screening in younger age groups, including those <25 years. From 30.066 liquid-based screening tests results (n = 30.066), 3849 liquid-based cytology, 1321 high-risk human papillomavirus (HRHPV) and 316 p16/Ki67 performed in women <30 years were selected. Performance characteristics were calculated for three screening models: primary HRHPV with p16/Ki67 triage, primary cytology with reflex HPV and primary cytology alone. Primary HRHPV with p16/Ki67 triage was significantly more sensitive in high-grade squamous intraepithelial lesion quantified with cervical intraepithelial neoplasia grade 2 or worse [HSIL(CIN2+)] detection than cytology with reflex HRHPV and cytology alone (83.3% vs. 70.8%/45.8%) and had significantly higher diagnostic predictive values (PPV:29.4%/21.3%/22.9%; NPV:91.7%/82.9%/82.2%, respectively at CIN2+ threshold). The number of colposcopies per HSIL(CIN2+) detection indices was 3.4, 4.7 and 4.4, respectively. Primary HPV testing in women <30 years with p16/Ki67 triage of HPV-positive cases might be an effective cervical cancer screening strategy for HSIL(CIN2+) detection with superior diagnostic performance when compared with primary cytology-based models. Women <25 years might also benefit from an introduction to a more sensitive screening approach.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 87%

Is Primary HPV with Secondary p16/Ki67 Dual-Stain an Alternative HSIL-Risk Detection Strategy in Cervical Cancer Screening for Women under 30 Years?

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In a recent meta-analysis, its sensitivity and specificity to detect cervical intraepithelial neoplasia of grade 2 (CIN2 + ), 3 or worse (CIN3 + ) ranged from 82–86% and 49–71%, respectively [ 41 ]. When combined with Ki67 IHC, p16 showed a sensitivity of 75.2% to detected CIN2 + , compared to 61.0% achieved by cytology alone [ 42 ]. In HNSCC, p16 IHC sensitivity to detect HPV-positive cases is high (92%, 95% CI 82–97%), while its specificity seems to be moderate (72%, 95% CI 45–89%) [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

HPV Infection Leaves a DNA Methylation Signature in Oropharyngeal Cancer Affecting Both Coding Genes and Transposable Elements

Camuzi¹,

Buexm²,

Lourenço

et al. 2021

Cancers

View full text Add to dashboard Cite

HPV oncoproteins can modulate DNMT1 expression and activity, and previous studies have reported both gene-specific and global DNA methylation alterations according to HPV status in head and neck cancer. However, validation of these findings and a more detailed analysis of the transposable elements (TEs) are still missing. Here we performed pyrosequencing to evaluate a 5-CpG methylation signature and Line1 methylation in an oropharyngeal squamous cell carcinoma (OPSCC) cohort. We further evaluated the methylation levels of the TEs, their correlation with gene expression and their impact on overall survival (OS) using the TCGA cohort. In our dataset, the 5-CpG signature distinguished HPV-positive and HPV-negative OPSCC with 66.67% sensitivity and 84.33% specificity. Line1 methylation levels were higher in HPV-positive cases. In the TCGA cohort, Line1, Alu and long terminal repeats (LTRs) showed hypermethylation in a frequency of 60.5%, 58.9% and 92.3%, respectively. ZNF541 and CCNL1 higher expression was observed in HPV-positive OPSCC, correlated with lower methylation levels of promoter-associated Alu and LTR, respectively, and independently associated with better OS. Based on our findings, we may conclude that a 5-CpG methylation signature can discriminate OPSCC according to HPV status with high accuracy and TEs are differentially methylated and may regulate gene expression in HPV-positive OPSCC.

show abstract

“…Tests for E6/E7 oncoproteins present a promising option for triaging screen-positive women given high positive predictive value and limited laboratory equipment ( 145 ). However, more than 60% of HPV positive women were also E6/E7 mRNA positive ( 146 ), which would present a challenge in identifying women with precancerous lesions. A systematic review of three types of HPV E6/E7 mRNA tests (Aptima, Quantivirus, and PreTect Proofer) found that while the tests have diagnostic relevance to detect CIN2-3, the higher specificity of some tests is due to the limited number of HPV types it detects ( 147 ).…”

Section: Resultsmentioning

confidence: 99%

A Framework for Cervical Cancer Elimination in Low-and-Middle-Income Countries: A Scoping Review and Roadmap for Interventions and Research Priorities

Shin

Gui

Mugo

et al. 2021

Front. Public Health

View full text Add to dashboard Cite

The World Health Organization announced an ambitious call for cervical cancer elimination worldwide. With existing prevention and treatment modalities, cervical cancer elimination is now within reach for high-income countries. Despite limited financing and capacity constraints in low-and-middle-income countries (LMICs), prevention and control efforts can be supported through integrated services and new technologies. We conducted this scoping review to outline a roadmap toward cervical cancer elimination in LMICs and highlight evidence-based interventions and research priorities to accelerate cervical cancer elimination. We reviewed and synthesized literature from 2010 to 2020 on primary and secondary cervical cancer prevention strategies. In addition, we conducted expert interviews with gynecologic and infectious disease providers, researchers, and LMIC health officials. Using these data, we developed a logic model to summarize the current state of science and identified evidence gaps and priority research questions for each prevention strategy. The logic model for cervical cancer elimination maps the needs for improved collaboration between policy makers, production and supply, healthcare systems, providers, health workers, and communities. The model articulates responsibilities for stakeholders and visualizes processes to increase access to and coverage of prevention methods. We discuss the challenges of contextual factors and highlight innovation needs. Effective prevention methods include HPV vaccination, screening using visual inspection and HPV testing, and thermocoagulation. However, vaccine coverage remains low in LMICs. New strategies, including single-dose vaccination could enhance impact. Loss to follow-up and treatment delays could be addressed by improved same-day screen-and-treat technologies. We provide a practical framework to guide cervical cancer elimination in LMICs. The scoping review highlights existing and innovative strategies, unmet needs, and collaborations required to achieve elimination across implementation contexts.

show abstract

p16/ki67 and E6/E7 mRNA Accuracy and Prognostic Value in Triaging HPV DNA-Positive Women

Cited by 50 publications

References 31 publications

Is Primary HPV with Secondary p16/Ki67 Dual-Stain an Alternative HSIL-Risk Detection Strategy in Cervical Cancer Screening for Women under 30 Years?

Is Primary HPV with Secondary p16/Ki67 Dual-Stain an Alternative HSIL-Risk Detection Strategy in Cervical Cancer Screening for Women under 30 Years?

HPV Infection Leaves a DNA Methylation Signature in Oropharyngeal Cancer Affecting Both Coding Genes and Transposable Elements

A Framework for Cervical Cancer Elimination in Low-and-Middle-Income Countries: A Scoping Review and Roadmap for Interventions and Research Priorities

Contact Info

Product

Resources

About