p16INK4aexpression as a potential marker of low-grade cervical intraepithelial neoplasia progression

Costa, Eloy da; Bastos, Larissa Brito; Triglia,; Marchi, Renata De; Júnior, F. de A. A. Camelo; Cavalcante, Marcondes; Andrade, Lucci De Angelo; Liliana, A

doi:10.1111/apm.12338

Cited by 10 publications

(8 citation statements)

References 28 publications

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“…Though CIN1 lesions with p16 staining had a higher tendency to progress to high grade lesions [25], it was difficult to predict the progression or regression of CIN1 [26]. Only a small area of the CIN1 lesions progressed to CIN2 or worse, and 15–30% of CIN2 or more severe lesions undergo regression [27, 28].…”

Section: Discussionmentioning

confidence: 99%

“…The positivity was 75% and the specificity was 1, indicating that the referral to treatment or operation would be reduced by 25% if p16/Ki-67/HPV load co-testing was used as an additional triage assessment in this population. However, both the p16/Ki-67/HPV load and p16/Ki-67 co-tests showed limited effects in the prediction of the progression of CIN1 lesions, though the presence of HPV DNA and p16 and Ki-67 staining were necessary to distinguish high-risk oncogenic cases from those of low-risk [19, 25, 30]. The prediction of either CIN1 progression or regression is challenging and can be influenced by the HPV genotype, genomic mutations, and host immune responses [4, 25].…”

Section: Discussionmentioning

confidence: 99%

“…However, both the p16/Ki-67/HPV load and p16/Ki-67 co-tests showed limited effects in the prediction of the progression of CIN1 lesions, though the presence of HPV DNA and p16 and Ki-67 staining were necessary to distinguish high-risk oncogenic cases from those of low-risk [19, 25, 30]. The prediction of either CIN1 progression or regression is challenging and can be influenced by the HPV genotype, genomic mutations, and host immune responses [4, 25]. We demonstrated that the assessment of the HPV load could improve the sensitivity of the p16/Ki-67 method for the diagnosis of CIN1 cases, but could not improve the prediction of the outcome of the lesions.…”

Section: Discussionmentioning

confidence: 99%

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Combining HPV DNA load with p16/Ki-67 staining to detect cervical precancerous lesions and predict the progression of CIN1–2 lesions

Liu

Gong

et al. 2019

Virol J

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Background Human Papilloma Virus (HPV) DNA tests are highly sensitive and can triage women with mild lesions, improving the prognosis and diagnosis of cervical lesions. However, additional efficient strategies should be developed to improve the specificity of these tests. Methods This study aimed to evaluate the clinical value of HPV DNA load in improving the diagnosis and prognosis of cervical lesions by p16/Ki-67 testing. Histological samples were collected from 350 women with HR-HPV genotyping and analyzed by qRT-PCR. Immunohistochemical staining was used to assess p16 and Ki-67 expression and clinical performance characteristics were calculated. Results Of the cases, 271 had detectable HR-HPV infection, in which HPV-16 was most prevalent (52.0%), followed by HPV-58 (22.5%). P16/Ki-67-positivity increased with histological severity but not for HR-HPV infection. Amongst the 13 HR-HPV genotypes, only HPV-16 (P = 0.016) and HPV-58 (P = 0.004) viral loads significantly correlated with lesion severity. The P16/Ki-67/HPV DNA load co-test indicated an increased sensitivity for the detection of cervical intraepithelial neoplasia (CIN) lesions compared to p16/Ki-67 staining in HPV-16 and/or 58 positive cases. Viral load did not improve the sensitivity of p16/Ki-67 co-test in non-HPV-16 or 58 positive cases. The clinical performance of the p16/Ki-67/HPV DNA load co-test was limited for the prediction of the outcome of CIN1 lesions. However, amongst the 12 HPV-16 and/or 58 positive CIN2 cases in which return visit results were obtained, the behavior of the lesions could be predicted, with a sensitivity, specificity, positive prediction rate (PPV), and negative prediction rate (NPV) of 0.667, 1, 1 and 0.5, respectively. Conclusion Combination of the assessment of HPV DNA load with the intensity of p16 and Ki-67 staining could increase the sensitivity of CIN lesion diagnosis and predict the outcome of CIN2 in patients with a HPV-16 and/or 58 infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Combining HPV DNA load with p16/Ki-67 staining to detect cervical precancerous lesions and predict the progression of CIN1–2 lesions

Liu

Gong

et al. 2019

Virol J

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“…Not all CIN lesions progress to high-grade disease; 90% of CIN1 resolve without treatment [24]. Thus, the natural progression of CIN is largely unpredictable, and histopathological examination cannot differentiate between lesions that will regress and those that will not [25].…”

Section: Discussionmentioning

confidence: 99%

c-myc Gene Copy Number Variation in Cervical Exfoliated Cells Detected on Fluorescence in situ Hybridization for Cervical Cancer Screening

Zhao

Hao²,

Cheng³

et al. 2016

Gynecol Obstet Invest

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Purpose: This study assessed the clinical significance of c-myc gene copy number gain detected by fluorescence in situ hybridization (FISH) in the prediction of cervical intraepithelial neoplasia (CIN) progression. Methods: We retrospectively investigated 140 Thinprep cytologic test (TCT) specimens that were histopathologically diagnosed with various stages of cervical neoplasia or malignancy. The specimens were subjected to TCT, human papillomavirus (HPV) testing, and FISH analysis with a c-myc-specific probe. The diagnostic reliability of these methods in determining progression was assessed according to sensitivity, specificity, and κ coefficients. Results: The gene copy number gain of c-myc was significantly higher in the cervical lesion of advanced histologic grade (p < 0.001). For CIN2+ lesions, the sensitivities of TCT, HPV DNA testing, and FISH analysis were 72.3, 92.1, and 64.5%, respectively; the specificities were 81.3, 57.8, and 93.8%, respectively (p < 0.001). The κ coefficients between the c-myc gene test and either the TCT or the HPV DNA test were 0.538 and 0.399, respectively (p < 0.001). Conclusions: FISH analysis of the c-myc oncogene could be a useful adjunct screening method for the early diagnosis of high-grade cervical lesions. Moreover, c-myc may be a new molecular biomarker for the early diagnosis of cervical lesion progression.

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“…Although many diagnostic techniques and therapeutic strategies for cervical cancer have improved, the overall prognosis of cervical cancer patients remains poor . Thus, a better understanding of the molecular mechanisms underlying cervical cancer development and progression is urgent for improving cervical cancer patients' prognosis .…”

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confidence: 99%

Long noncoding RNA PVT1 promotes cervical cancer progression through epigenetically silencing miR‐200b

Zhang

Liu

2016

APMIS

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Long noncoding RNA PVT1 has been reported to be dysregulated and play vital roles in a variety of cancers. However, the functions and molecular mechanisms of PVT1 in cervical cancer remain unclear. The objective of this study was to investigate the expression, clinical significance, biological roles, and underlying functional mechanisms of PVT1 in cervical cancer. Our results revealed that PVT1 is upregulated in cervical cancer tissues. Enhanced expression of PVT1 is associated with larger tumor size, advanced International Federation of Gynecology and Obstetrics stage, and poor prognosis of cervical cancer patients. Using gain-of-function and loss-of-function approaches, we demonstrated that overexpression of PVT1 promotes cervical cancer cells proliferation, cell cycle progression and migration, and depletion of PVT1 inhibits cervical cancer cell proliferation, cell cycle progression, and migration. Mechanistically, we verified that PVT1 binds to EZH2, recruits EZH2 to the miR-200b promoter, increases histone H3K27 trimethylation level on the miR-200b promoter, and inhibits miR-200b expression. Furthermore, the effects of PVT1 on cervical cell proliferation and migration depend upon silencing of miR-200b. Taken together, our findings confirmed that PVT1 functions as an oncogene in cervical cancer and indicated that PVT1 is not only an important prognostic marker, but also a potential therapy target for cervical cancer.

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p16^INK^4aexpression as a potential marker of low-grade cervical intraepithelial neoplasia progression

Cited by 10 publications

References 28 publications

Combining HPV DNA load with p16/Ki-67 staining to detect cervical precancerous lesions and predict the progression of CIN1–2 lesions

Combining HPV DNA load with p16/Ki-67 staining to detect cervical precancerous lesions and predict the progression of CIN1–2 lesions

<b><i>c-myc</i></b> Gene Copy Number Variation in Cervical Exfoliated Cells Detected on Fluorescence in situ Hybridization for Cervical Cancer Screening

Long noncoding RNA PVT1 promotes cervical cancer progression through epigenetically silencing miR‐200b

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