HPV genotyping and p16/Ki-67 test significantly improve detection rate of high-grade cervical squamous intraepithelial lesion

Lewitowicz, Piotr; Nasierowska‐Guttmejer, Anna; Rokitaⴕ, Wojciech; Adamczyk-Gruszka, Olga; Głuszek, Stanisław; Chrapek, Magdalena; Kołos, Małgorzata; Wrona-Cyranowska, Agnieszka; Misiek, Marcin

doi:10.5114/aoms.2018.80697

Cited by 16 publications

(13 citation statements)

References 23 publications

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“…For the above, we proposed a panel of three cellular biomarkers (TOP2A/MCM2, p16 INK4a , and cyclin-E), which, according to the statistical analysis and their function, are the most useful for evaluating the exacerbated proliferative activity of cervical cells, which is one of the earliest hallmarks of carcinogenesis. Other studies also indicated the usefulness of a biomarkers panel, based on the dual detection of p16 INK4a /Ki-67 for the screening of cervical lesions induced by HPV [ 13 , 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…In differentiated epithelial cells, p16 INK4a expression is not detected; however, in dysplastic cervical epithelial cells and HPV-positive CC cells, p16 INK4a is overexpressed [ 7 ]. Another marker of cell proliferation is Ki-67, which is only expressed in growing cells [ 13 ]. In addition, overexpression of MCM2 and TOP2A has been reported as a potential diagnostic biomarker in CC [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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TOP2A/MCM2, p16INK4a, and cyclin E1 expression in liquid-based cytology: a biomarkers panel for progression risk of cervical premalignant lesions

et al. 2021

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Background To improve the efficiency of early diagnosis systems for cervical cancer, the use of cellular and viral markers for identifying precancerous lesions with a greater probability to progress to cancer has been proposed. Several cellular proteins and markers of oxidative DNA damage have been suggested as possible biomarkers of cervical carcinogenesis; however, they have not been evaluated together. In this study, we analyzed the expression of the cellular markers p16INK4a, Ki-67, CyclinE1, TOP2A/MCM2, and telomerase, as well as the DNA oxidative damage markers ROS and 8-OHdG. The analyses were performed in liquid-based cervical cytology samples or biopsies with premalignant lesions or cervical cancer diagnosis, with the purpose of selecting a panel of biomarkers that allow the identification of precursor lesions with greater risk of progression to cervical cancer. Methods We analyzed 1485 liquid-based cytology samples, including 239 non-squamous intraepithelial lesions (NSIL), 901 low-grade squamous intraepithelial lesions (LSIL), 54 high-grade squamous intraepithelial lesions (HSIL), and 291 cervical cancers (CC). The biomarkers were analyzed by immunocytochemistry and Human Papilloma Virus (HPV) genotyping with the INNO-LiPA genotyping Extra kit. Results We found that all tested cellular biomarkers were overexpressed in samples with high risk-HPV infection, and the expression levels increased with the severity of the lesion. TOP2A/MCM2 was the best biomarker for discriminating between LSIL and HSIL, followed by p16INK4a and cyclinE1. Statistical analysis showed that TOP2A/MCM2 provided the largest explanation of HSIL and CC cases (93.8%), followed by p16INK4a (91%), cyclin E1 (91%), Ki-67 (89.3%), and telomerase (88.9%). Conclusions We propose that the detection of TOP2A/MCM2, p16INK4a and cyclin E1 expression levels is useful as a panel of biomarkers that allow identification of cervical lesions with a higher risk for progression to CC with high sensitivity and precision; this can be done inexpensively, in a single and non-invasive liquid-based cytology sample.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TOP2A/MCM2, p16INK4a, and cyclin E1 expression in liquid-based cytology: a biomarkers panel for progression risk of cervical premalignant lesions

et al. 2021

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“…The launch of the LBC has improved the accuracy ratio of HSIL and decreased the ASC-US ratio. Moreover, to fix that problem the p16/Ki67 test and hrHPV genotyping were also employed [16][17][18][19][20][21]. Finally, well-designed categorisation with the assistance of cutting-edge solutions allows a very high level of accuracy.…”

Section: Cervical Cytologymentioning

confidence: 99%

Unified cytological reports determine the clinical management

Żelezik¹,

Michalska²,

Radowicz-Chil³

et al. 2019

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All types of cytological procedures bear a burden of unequivocal reports and confusion with setting a proper clinical procedure. In 1989, The Bethesda System (TBS) was introduced to resolve many concerns in the matter of unclear classification of changes in cervical cytology. The guidelines of TBS were based on the clinical data provided, the quality of the smear assessment, unification of terminology, and updated knowledge about changes underlying cell abnormalities. It is believed that both TBS and thyroid TBS inspired the members of the Papanicolaou Society of Cytology to design and publish a modern approach to pancreatic lesion description. The presented proposal created a strong foundation for clinical management and revealed a serious risk of underdiagnosis. In light of the short time since the launch of this guide, more time is needed to estimate its impact, especially since only a few clinical centres have implemented it to this day. Streszczenie Wszystkich typów badań cytologicznych dotyczy problem dwuznacznych wyników, które utrudniają wdrożenie właściwych procedur leczniczych. Aby rozwiać wiele wątpliwości wynikających z niejasnej klasyfikacji zmian w cytologii szyjki macicy, w 1989 roku stworzono system określony od miejsca powstania jako "Bethesda system". Jego podstawowe zasady oparto na dostarczonych danych klinicznych, ocenie jakości materiału, ujednoliceniu terminologii, jak również na zaktualizowanej wiedzy o zmianach patologicznych w komórkach. Po zakończonym sukcesem włączeniu go do użytku podobne rozwiązania wdrożono do raportowania biopsji tarczycy. Można podejrzewać, że to zainspirowało członków Papanicolau Society of Cytology do opublikowania systemu klasyfikacji zmian guzowatych trzustki. Z perspektywy czasu można powiedzieć, że system Bethesda oceny zmian w szyjce macicy i w tarczycy został bardzo chętnie zaakceptowany przez patologów i klinicystów, a przedstawione klasyfikacje stworzyły fundament dla ujednoliconego postępowania klinicznego. Wydaje się, że obiektywna ocena wpływu przedstawionych propozycji na proces diagnostyczny wymaga więcej czasu.

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“…Its genesis is commonly associated with human papillomavirus (HPV), human herpesvirus II, and cytomegalovirus [2]. HPV infections are considered to be primarily responsible for the disease [3][4][5]. Increasingly, more authors focus on Epstein-Barr virus (EBV) as a player in the onco-genesis of carcinoma of the cervix [6,7].…”

Section: Introductionmentioning

confidence: 99%

Warty carcinoma of the uterine cervix: a virus-induced disease?

et al. 2020

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Introduction: Warty carcinoma (WC) of the uterine cervix is a rare subtype of squamous-cell carcinoma (SCC), and its frequency, clinical behaviour, and aetiology are obscure. It originates from condylomas, and a viral carcinogenesis seems logical. Material and methods: Retrospective analysis was performed of all cervical carcinomas (CC), diagnosed at a single institution for a 10-year period. Analysed patients had stage I carcinoma. Patients with WC were identified, and their tumour samples were tested for high-risk HPV (hr-HPV) and EBV, using PCR and ISH. Clinical characteristics and WC rates across all stage I CC patients were assessed. All patients had minimum 3-year follow-up, and overall survival (OS) and 5-year survival rates were calculated. Results: WC comprised 2.2% of all stage I CC (n = 630). The mean age of the patients was 48 years (range: 29-72). The primary tumour size was 2 cm in 4 (28.6%) patients, 2-4 cm in 2 (14.3%) patients, and 4 cm in 8 (57.1%) patients. Lymph node metastasis was found in 1 (7.1%) patient. EBV or hr-HPV were detected in 2 (18.2%) patients using ISH, with no coinfection reported. Hr-HPV was detected in 2 (18.2%) patients; EBV in 4 (36.4%) cases, and in 2 of them (18.2%) there was a co-infection. Thirteen patients had a follow-up of ≥ 5 years and their 5-year OS was 100%. Conclusions: WC is a rare subtype of SCC with good prognosis, regardless of viral status. In contrast to SCC, its aetiology is not related to hr-HPV. The role of EBV remains unclear and cannot currently be denied.

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HPV genotyping and p16/Ki-67 test significantly improve detection rate of high-grade cervical squamous intraepithelial lesion

Cited by 16 publications

References 23 publications

TOP2A/MCM2, p16INK4a, and cyclin E1 expression in liquid-based cytology: a biomarkers panel for progression risk of cervical premalignant lesions

TOP2A/MCM2, p16INK4a, and cyclin E1 expression in liquid-based cytology: a biomarkers panel for progression risk of cervical premalignant lesions

Unified cytological reports determine the clinical management

Warty carcinoma of the uterine cervix: a virus-induced disease?

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