Role of quantitative p16INK4A mRNA assay and digital reading of p16INK4A immunostained sections in diagnosis of cervical intraepithelial neoplasia

Vasiljević, Nataša; Carter, Paul D.; Reuter, Caroline; Warman, Rhian; Brentnall, Adam R.; Carton, James; Cuzick, Jack; Lörincz, Attila T.

doi:10.1002/ijc.30783

Cited by 9 publications

(7 citation statements)

References 32 publications

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“…Furthermore, we measured expression levels of P16, which has been reported to participate in cell cycle regulation and is now used for the clinical detection of HSIL in cervical cancer patients. [30][31][32][33][34] We found that LRP11 expression correlated with cancer differentiation and could be used as a prognostic marker, an advantage over P16 measurement. Consistent with our results, Hoang's study also found that osteosarcoma patients with positive LRP5 expression showed a trend on decreased of event-free survival.…”

Section: Discussionmentioning

confidence: 84%

“…In the present study, to verify the results of the bioinformation analysis, we performed Western blots and IHC, and the results were consistent. Furthermore, we measured expression levels of P16, which has been reported to participate in cell cycle regulation and is now used for the clinical detection of HSIL in cervical cancer patients 30–34. We found that LRP11 expression correlated with cancer differentiation and could be used as a prognostic marker, an advantage over P16 measurement.…”

Section: Discussionmentioning

confidence: 94%

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The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer

Wang

Han

You

et al. 2019

CMAR

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Background It is unclear whether low density lipoprotein receptor-related protein 11 (LRP11), a newly found lipoprotein receptor regulatory protein, has the carcinogenic effects in cervical cancer. Methods Bioinformatics analysis, immunohistochemical (IHC) staining and evaluation, cell proliferation assay, flow cytometry, transwell migration and invasion assays, Western blotting, growth of LRP11-silenced cells in athymic nude mice were performed in this research. Results We found that LRP11 expression was higher in high-grade squamous intraepithelial lesions (HSIL) and cervical cancer tissue than in normal cervix, and high expression of LRP11 was associated with differentiation degree ( P =0.0266), indicating poor prognosis ( P =0.0210). The silencing of LRP11 in SiHa and CaSki cell lines inhibited cell proliferation, reduced migration and invasion and suppressed cell growth in nude mice, which possibly related to cell cycle protein regulation of CDK 2/4, cyclin D1/E1, MMP-2/9, and VEGF. Furthermore, LRP11 showed substantial positive correlation with P16 in vivo and in vitro. Conclusion LRP11 plays important roles in proliferation, migration and invasion, with the potential to be a useful prognostic marker and therapeutic target for patients with HSIL and cervical cancer.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 94%

The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer

Wang

Han

You

et al. 2019

CMAR

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“…These procedures were repeated 5 times and then we dried the plate ( 6 ). Enzyme loading: we added 50 µL of enzyme conjugate to each well, excluding the blank wells ( 7 ). Incubation: the same as step 3 ( 8 ).…”

Section: Methodsmentioning

confidence: 99%

“…The available studies suggest that 75% of sexually active women will have at least one HR-HPV infection in their lifetime, of which 90% are transient and only 10% of patients develop a persistent infection. Approximately 5% of persistent infections will also progress to CIN ( 4 - 7 ).…”

Section: Introductionmentioning

confidence: 99%

The correlation of HPV16 and HPV18 with local vaginal immunity after the treatment of cervical intraepithelial neoplasia

Mu¹,

Miao²,

Song³

2020

Transl Cancer Res TCR

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Background This study aimed to investigate the correlation between the level of HPV16 and HPV18 in patients with cervical lesions and the local vaginal immunity after receiving treatment with different degrees of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC). Methods One hundred and thirty-six patients with LSIL (grade 1 CIN or CIN 1), 263 patients with HSIL (grade 2 and 3 CIN or CIN 2 and 3), and 33 patients with CSCC pathologically confirmed between November 2012 and September 2016 were assigned to the test group and 100 healthy women in the same period were assigned to the control group. ELISA was used to determine the levels of SIgA, IgG, IL-2, and IL-10 and the IL-2/IL-10 ratio in vaginal lavage fluid in the test group (before treatment and 3, 6, and 12 months after treatment) and the control group, respectively. Gene chip technology was adopted to test the HPV infection in the test group (before treatment and 3, 6, and 12 months after treatment) and the control group, respectively. Results The results showed that the levels of SIgA, IgG, and IL-10 were positively correlated with the degree of cervical lesions and IL-2/IL-10 was negatively correlated with the degree in all patients before treatment. The levels of SIgA, IgG, and IL-10 were positively correlated with the degree of cervical lesions and IL-2/IL-10 was negatively correlated with the degree in HPV16 and HPV18-infected patients before receiving the treatment. Conclusions The recovery after the treatment of HPV infection is time-dependent and the immune system of patients with CIN starts to recover in the 6th month after treatment, early intervention is not recommended. However, the immune system is approximately in a normal sate at 12 months after treatment, at which time the efficacy can be evaluated, and clinical intervention can be initiated if necessary. The level of local immune factors in the vagina can be monitored to determine the progression and prognosis of patients’ cervical lesions.

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“…The most relevant clinical use of immunoassays in cervical cancer diagnostics is based on IHC, where antibodies are used to visualize specific proteins on cells or tissues followed by their microscopic analysis. IHC staining of p16, an inhibitor of cyclin-dependent kinases, and Ki-67, a cell proliferation marker, showed potential for improving diagnostic accuracy [41,42]. The p16/Ki-67 dual staining technology is more sensitive than cytology in detecting CIN2+ in hrHPV-positive women and can be used for triage after a positive hrHPV test to guide the decision on how to follow-up, for example, by colposcopy [43,44].…”

Section: Immunoassaysmentioning

confidence: 99%

Molecular markers for cervical cancer screening

Güzel

Hoff

Kok

et al. 2021

Expert Review of Proteomics

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This review gives an overview of current screening practices for cervical cancer. In the introduction, we will cover approaches of population screening focusing on high-risk Human Papilloma Virus (hrHPV) and the need for a better triage assay. We will further assess the impact of current vaccination programs on screening. Subsequently, the review will cover various technological aspects of nucleic acid-and protein-based biomarker assays. We will then detail different molecular markers in view of their use in triage assays, emphasizing epigenetic and protein markers. Finally, we will place this in the context of cost-effectiveness considerations in view of their implementation in high-as well as in low-to middle-income countries. Introduction: Cervical cancer remains a significant healthcare problem, notably in low-to middle-income countries. While a negative test for hrHPV has a predictive value of more than 99.5%, its positive predictive value is less than 10% for CIN2+ stages. This makes the use of a so-called triage test indispensable for population-based screening to avoid referring women, that are ultimately at low risk of developing cervical cancer, to a gynecologist. This review will give an overview of tests that are based on epigenetic marker panels and protein markers. Areas covered: There is a medical need for molecular markers with a better predictive value to discriminate hrHPV-positive women that are at risk of developing cervical cancer from those that are not. Areas covered are epigenetic and protein markers as well as health economic considerations in view of the fact that most cases of cervical cancer arise in low-to-middle-income countries. Expert opinion: While there are biomarker assays based on changes at the nucleic acid (DNA methylation patterns, miRNAs) and at the protein level, they are not widely used in population screening. Combining nucleic acid-based and protein-based tests could improve the overall specificity for discriminating CIN2+ lesions that carry a low risk of progressing to cervical cancer within the screening interval from those that carry an elevated risk. The challenge is to reduce unnecessary referrals without an undesired increase in false-negative diagnoses resulting in cases of cervical cancer that could have been prevented. A further challenge is to develop tests for low-and middle-income countries, which is critical to reduce the worldwide burden of cervical cancer.

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Role of quantitative p16^INK4A mRNA assay and digital reading of p16^INK4A immunostained sections in diagnosis of cervical intraepithelial neoplasia

Cited by 9 publications

References 32 publications

<p>The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer</p>

<p>The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer</p>

The correlation of HPV16 and HPV18 with local vaginal immunity after the treatment of cervical intraepithelial neoplasia

Molecular markers for cervical cancer screening

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