Search

Background: HPV-independent cervical cancers (HPV-ind CCs) are uncommon with worse prognosis and poorly understood. This study investigated the molecular characteristics of HPV-ind CCs, aiming to explore new strategies for HPV-ind CCs., Methods: HPV status of 1010 cervical cancer patients were detected by RT-PCR, PCR and RNA-sequencing (RNA-seq). Whole exome sequencing (WES) and RNA-seq were performed in identified HPV-ind CCs. The efficacy of PI3Kα inhibitor BYL719 in HPV-ind CCs was evaluated in cell lines, patient-derived organoids (PDOs) and patient-derived xenografts (PDXs)., Results: Twenty-five CCs were identified as HPV-ind, which were more common seen in older, adenocarcinoma patients and exhibited poorer prognosis as well as higher tumor mutation burden compared to HPV-associated CCs. HPV-ind CCs were featured with highly activated PI3K/AKT signaling pathway, particularly, PIK3CA being the most predominant genomic alteration (36%). BYL719 demonstrated superior tumor suppression in vitro and in vivo. Furthermore, HPV-ind CCs were classified into two subtypes according to distinct prognosis by gene expression profiles, the metabolism subtype and immune subtype., Conclusions: This study reveals the prevalence, clinicopathology, and molecular features of HPV-ind CCs and emphasizes the importance of PIK3CA mutations and PI3K pathway activation in tumorigenesis, which suggests the potential significance of PI3Kα inhibitors in HPV-ind CC patients., (© 2024. The Author(s).)

Targeting programmed death 1(PD-1) has been approved for relapsed cervical cancer with unsatisfactory clinical efficacy. This study aims to analyse the impact of PI3K pathway activation on tumour immune microenvironment and evaluates the immune sensitization effect by PI3K inhibition in cervical cancer. The effect of PIK3CA mutation on PD-L1 expression and CD8+ T cells differentiation was determined in cervical cancer tissues. Luciferase and ChIP-qPCR/PCR assays were used to determine the transcriptional regulation of PD-L1 by PIK3CA-E545K. The effects of PI3K inhibitor treatment on immune environment in vitro and in vivo were evaluated by RNA sequencing (RNA-seq) and flow cytometry. The efficacy of PI3K inhibitor and anti-PD-1 therapy was assessed in cell-derived xenografts (CDX) and patients-derived xenografts (PDX). PD-L1 overexpression is more frequently observed in elder women with squamous cervical carcinoma. It predicts longer progress-free survival and overall survival. PIK3CA mutation results in increased mRNA and protein levels of PD-L1, the repression of CD8+ T cell differentiation in cervical cancer. Here, we report a case that continuous pembrolizumab monotherapy treatment induced complete remission of a recurrent cervical cancer patient with systemic metastasis and PIK3CA-E545K mutation, implying that PIK3CA mutation is potentially a biomarker for pembrolizumab treatment in cervical cancer. Specifically, this mutation promotes the expression of PD-L1 by upregulating the transcription factor IRF1. PI3Kα-specific inhibitor markedly activates immune microenvironment by regulating the PD-1/L1-related pathways and promoting CD8+ T cell differentiation and proliferation in Caski-CDXs with PIK3CA-E545K mutation. PI3Kα inhibitor significantly enhances the anti-tumour efficacy of PD-1 blockade in CDXs and PDXs. PIK3CA mutations may predict the response of cervical cancer to PD-1 blockade. The efficacy of PI3Kα inhibitors combined with PD-1 antibodies is promising in cervical cancer and warrants additional clinical and mechanistic investigations., (© 2023 The Authors. Immunology published by John Wiley & Sons Ltd.)

The mutation of glutamic acid 545 to lysine (E545K) in PIK3CA, as the most common missense mutation of this gene in various cancer types, is frequently observed in cervical cancer and has been shown to reduce cervical cancer radiosensitivity. However, the underlying mechanisms remain unclear. Here, we implicate the alterations of glutamine metabolism in PIK3CA-E545K-mediated radioresistance of cervical cancer. Specifically, PIK3CA mutation negatively regulated the expression of SIRT4 via the epigenetic regulator EP300 independently of the canonical mTORC1 pathway. PIK3CA-E545K-induced SIRT4 downregulation promoted cell proliferation, migration, and radiation-induced DNA repair and apoptosis, while SIRT4 overexpression reversed the radioresistance phenotype mediated by PIK3CA mutation. Mechanistically, SIRT4 modulated glutamine metabolism and thus cellular apoptosis by negatively regulating a glutamate pyruvate transaminase GPT1. Moreover, the PI3K inhibitor BYL719, but not mTOR inhibitors, exerted remarkable synergistic effects with radiotherapy by inhibiting glutamine metabolism in vitro and in vivo. Collectively, this study reveals the role of PIK3CA-E545K-SIRT4 axis in regulating glutamine metabolism and the radioresistance in cervical cancer, which provides a necessary preliminary basis for clinical research of PI3K inhibitors as radiosensitizing agents., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Small cell neuroendocrine carcinoma of the cervix (SCNEC) is a lethal malignancy and little treatment progress has been made for decades. We sought to map its genetic profiles, and identify whether SCNEC harbor mutations and potential targets for therapeutic interventions., Methods: Primary tumor tissue and blood samples were obtained from 51 patients with SCNEC. The next-generation sequencing was carried out to detect mutations of 520 cancer-related genes, including the entire exon regions of 312 genes and the hotspot mutation regions of 208 genes. Quantitative multiplex PCR was performed for the detection of seven high-risk HPV types., Results: Of the 51 detected patients, 92.16% were positive for HPV 18. Ninety-eight percent of cases harbored genetic alterations. Two cases were observed with hypermutated phenotype and determined as MSI-H/dMMR. Genetic mutations were clustering in RTK/RAS(42.86%), PI3K-AKT(38.78%), p53 pathway(22.45%) and MYC family(20.41%). Mutations in genes involved in the p53 pathway indicate a poorer prognosis (3-year OS, 33.5% vs 59.9%, p = 0.031). A total of seven patients harboring mutations in homogeneous recombination repair (HRR) genes were reported. In addition, IRS2 and SOX2 were amplified in 14.9% and 6.12% of SCNEC patients, respectively., Conclusions: SCNEC is specifically associated with HPV 18 infection. Its genetic alterations are characterized by a combined feature of high-risk HPV driven events and mutations observed in common neuroendocrine carcinoma. We identified several targetable mutated genes, including KRAS, PIK3CA, IRS2, SOX2, and HRR genes, indicating the potential efficacy of target therapies in these patients. MSI-H/dMMR individuals may benefit from checkpoint blockade therapies., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

Regulatory T cells (Tregs) are crucial for the maintenance of peripheral tolerance, but they also limit beneficial responses through cancer-induced immunoediting. The roles of Treg subsets in cervical squamous cell carcinoma (CSCC) are currently unknown. Here, we aimed to perform an extensive study with an increased resolution of the Treg compartment in the peripheral blood and tumor tissues of CSCC patients. We first identified that an HLADR hi Treg population in the peripheral blood was significantly increased in CSCC patients compared to precancer patients and healthy donors. We found that HLADR hi Tregs express high levels of a panel of inhibition and activation markers and the TCR-responsive transcription factors BATF and IRF4. However, this Treg subset showed reduced calcium influx after TCR crosslinking. In addition, HLADR hi Tregs are highly proliferative and vulnerable to apoptosis. Further studies demonstrated that the HLADR hi Tregs display high levels of suppressive activity. Quantitative multiplexed immunohistochemistry revealed that an increase in the number of tumor-infiltrating HLADR hi Tregs is associated with unfavorable classical risk parameters of advanced disease stage and stromal invasion. Context-based quantification revealed that a high frequency of stromal HLADR hi Tregs in patients is significantly associated with worse progression-free survival. In the current study, we characterized a population of highly activated and immunosuppressive HLADR hi Tregs in CSCC patients. An increased HLADR hi Treg frequency may be a potential biomarker to stratify CSCC patients and evaluate therapeutic efficacies in personalized immuno-oncology studies., (© 2019 UICC.)

Background: Alterations in peripheral blood lymphocytes in cervical cancer have been reported, although conflicting views exist. The present study investigated the distributions of lymphocyte subsets in tumor tissue and peripheral blood samples from cervical cancer patients and precancerous lesion patients, and evaluated the correlations of lymphocyte subsets with clinicopathological and prognostic variables., Methods: A total of 44 patients with stage IB1-IIA2 cervical cancer and 13 precancerous lesion patients were included. Lymphocytes were collected from the tumor tissue and the peripheral blood, and isolated by Lymphoprep density gradient centrifugation. The percentages of lymphocyte subsets were quantified by flow cytometry analysis, and the differences between lymphocyte subsets in the tumor tissue and peripheral blood were compared by SPSS. In addition, the relationships between lymphocyte subsets and clinicopathological and prognostic variables were analyzed., Results: Our results revealed that the amount of total T lymphocytes, CD8+ T cells, granulocytes, pDCs, CD16+ monocytes and CD56 high NK cells were significantly higher in the tumor tissue than in the peripheral blood in the cervical cancer patients, while those of CD4+ T cells, CD4+/CD8+ cell ratio, rdT cells, BDCA1+ mDCs, total monocytes, CD14+ monocytes, NK cells and CD56 low NK cells exhibited the opposite trend (p < 0.05). The levels of total pDCs and BDCA1+ mDCs in the peripheral blood were significantly lower in the cervical cancer patients than in the precancerous lesion patients, while the proportion of CD16+ monocytes was elevated (p < 0.05). In addition, some lymphocyte subsets, especially CD4+ cells and CD8+ cells, and the CD4+/CD8+ cell ratio were closely associated with clinicopathological and prognostic parameters., Conclusions: These results suggested that distinct alterations in infiltrating lymphocyte subsets occurred in the tumor and were associated with clinicopathological and prognostic parameters. Systemic impairment of the immune system may occur in the antitumor response of cervical cancer patients.

Background: To study the kinetic profile and clinicopathological implications of squamous cell carcinoma antigen (SCC-Ag) in cervical cancer patients who underwent surgery by a self-developed SCC-Ag single molecule assay (Simoa) prototype immunoassay., Methods: Participants were prospectively enrolled between 04/2016 and 06/2017. Consecutive serum samples were collected at five points: day 0 (the day before surgery), postoperative day 4, weeks 2-4, months 2-4 and months 5-7. In total, 92 patients and 352 samples were included. The kinetic change in SCC-Ag levels and their associations with clinicopathological characteristics were studied., Results: Simoa SCC-Ag was validated by comparison with the Architect assay. SCC-Ag levels measured by the Simoa assay were highly correlated with the Architect assay's levels (Pearson's correlation coefficient = 0.979, Passing-Bablok regression slope 0.894 (0.847 to 0.949), intercept - 0.009 (- 0.047 to 0.027)). The median values for each time-point detected by the Simoa assay were 2.49, 0.66, 0.61, 0.72, and 0.71 ng/mL, respectively. The SCC-Ag levels decreased dramatically after surgery and then stabilized and fluctuated to some extent within 6 months. Patients with certain risk factors had significantly higher SCC-Ag values than their negative counterparts before surgery and at earlier time points after surgery, while no difference existed at the end of observation. Furthermore, although patients with positive lymph nodes had sustained higher SCC-Ag levels compared to those with negative lymph nodes, similar kinetic patterns of SCC-Ag levels were observed after surgery. Patients who received postoperative treatment had significantly higher SCC-Ag values than those with surgery only at diagnosis, while no difference existed after treatment., Conclusions: The Simoa SCC-Ag prototype was established for clinical settings. The SCC-Ag levels were higher in patients with risk factors, whereas the kinetic trend of SCC-Ag might be mainly affected by postoperative adjuvant therapy. These data indicate that the SCC-Ag level might be a good predictor for the status of cervical cancer, including disease aggressiveness and treatment response.

This study aims to explore whether E545K, the most common hotspot mutation of PIK3CA in cervical cancer, confers radioresistance to cervical cancer cells, to demonstrate the underling mechanism, and to develop the effective targets. SiHa and MS751 cells with PIK3CA -WT and PIK3CA -E545K were established by lentiviral transfection. The radiosensitivity was assessed by colony formation, cell cycle, cell apoptosis, DNA damage, and repair assay. The growth and immunohistochemical assay of xenograft tumor-related toxicity were evaluated in vivo It was indicated that more cells with PIK3CA -E545K arrested in S phase. Irradiation (IR) led to more survival percentage, less apoptosis, fewer pH2A.X foci, and higher expression of Chk1/2 in SiHa and MS751 cells bearing PIK3CA -E545K. Mechanically, AKT/GSK3β/β-catenin pathway was highly activated, and more β-catenin was found accumulated in nucleus in cells with PIK3CA -E545K after IR. Furthermore, targeting β-catenin by shRNA or XAV939 enhanced IR sensitivity in cells with PIK3CA -WT and PIK3CA -E545K, whereas it was more notably in the latter. β-Catenin shRNA and XAV939 increased IR-mediated inhibition of colony formation with highly activated p53/bcl2/bax pathway. XAV939 enhanced IR-caused apoptosis, DNA damage, overcame S-phase arrest, DNA repair and reversed β-catenin nuclear accumulation in MS751 cells with PIK3CA -E545K. In vivo , XAV939 enhanced the radiosensitivity of cervical cancer xenografts with PIK3CA -E545K with invisible viscera toxicity. The findings demonstrate that cervical cancer cells with PIK3CA -E545K are resistant to IR by enhancing the expression and nuclear accumulation of β-catenin. Targeting β-catenin reverses the radioresistance, which suggests possible areas for preclinical research on β-catenin inhibition for strengthening the radiosensitivity of cervical cancer., (©2019 American Association for Cancer Research.)

Background: The study aims to present the effect of PIK3CA E542K and E545K mutations on glucose metabolism and proliferation and identify their underlying mechanisms in cervical cancer., Methods: The maximum standard uptake value (SUV max ) of tumors was detected by 18 F-FDG PET/CT scan. In vitro, glycolysis analysis, extracellular acidification rate analysis, and ATP production were used to evaluate the impact of PIK3CA E542K and E545K mutations on glucose metabolism. The expression level of key glycolytic enzymes was evaluated by western blotting and immunohistochemical staining in cervical cancer cells and tumor tissues, respectively. Immunofluorescence analysis was used to observe the nuclear translocation of β-catenin. The target gene of β-catenin was analyzed by using luciferase reporter system. The glucose metabolic ability of the xenograft models was assessed by SUV max from microPET/CT scanning., Results: Cervical cancer patients with mutant PIK3CA (E542K and E545K) exhibited a higher SUV max value than those with wild-type PIK3CA (P = 0.037), which was confirmed in xenograft models. In vitro, enhanced glucose metabolism and proliferation was observed in SiHa and MS751 cells with mutant PIK3CA. The mRNA and protein expression of key glycolytic enzymes was increased. AKT/GSK3β/β-catenin signaling was highly activated in SiHa and MS751 cells with mutant PIK3CA. Knocking down β-catenin expression decreased glucose uptake and lactate production. In addition, the nuclear accumulation of β-catenin was found in SiHa cells and tumors with mutant PIK3CA. Furthermore, β-catenin downregulated the expression of SIRT3 via suppressing the activity of the SIRT3 promotor, and the reduced glucose uptake and lactate production due to the downregulation of β-catenin can be reversed by the transfection of SIRT3 siRNA in SiHa cells with mutant PIK3CA. The negative correlation between β-catenin and SIRT3 was further confirmed in cervical cancer tissues., Conclusions: These findings provide evidence that the PI3K E542K and E545K/β-catenin/SIRT3 signaling axis regulates glucose metabolism and proliferation in cervical cancers with PIK3CA mutations, suggesting therapeutic targets in the treatment of cervical cancers., Trial Registration: FUSCC 050432-4-1212B. Registered 24 December 2012 (retrospectively registered).

Objective: ERBB2 mutations have been found in a subset of invasive cervical cancer (ICC). Nevertheless, the prevalence, mutation spectrum, clinicopathological relevance, human papillomavirus (HPV)-genotype association and prognostic significance of ERBB2-mutated ICCs have not been well established., Methods: In this study, ICC samples (N=1015) were assessed for mutations in ERBB2, KRAS, and PIK3CA by cDNA-based Sanger sequencing., Results: Somatic ERBB2 mutations were detected in 3.15% patients. The ERBB2 mutation rate was significantly higher in adenocarcinoma (4.52%, 7/155), adenosquamous carcinoma (7.59%, 6/79) and neuroendocrine carcinoma (10.34%, 3/29) than that in squamous carcinoma (2.14%, 16/749) (P=0.004, Fisher exact test). In addition, 18.75% of the patients carrying ERBB2 mutations concomitantly harbored PIK3CA or KRAS mutations. Patients with ERBB2-mutated ICCs tended to have a worse prognosis than those with wild-type or PIK3CA-mutated ICCs but a better prognosis than those with KRAS-mutated ICCs., Conclusions: This study provided a promising rationale for the clinical investigation of tyrosine kinase inhibitors for the treatment of cervical cancer with ERBB2 mutations. Patients with non-squamous cell carcinomas have priority as candidates for ERBB2-targeted therapy. Concurrent PIK3CA/RAS mutations should be considered in the design of clinical trials., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The predictive and prognostic role of KRAS mutations in cervical cancer remains inconclusive. The aim of this study was to explore the clinicopathological and prognostic relevance of KRAS mutations in invasive cervical cancers (ICC)., Methods: Reverse transcription polymerase chain reaction (PCR) and Sanger sequencing were employed to detect KRAS mutations in 876 ICC patients. Quantitative real-time PCR was used to detect human papillomavirus (HPV) 16 and HPV 18., Results: Non-synonymous mutations of KRAS were identified in 30 (3.4%) patients. These mutations were more common in non-squamous cell carcinoma than in squamous cell carcinoma (SCC) (8.2% vs. 2.2%, respectively, p<0.001) and were associated with HPV 18 infection (p=0.003). The prevalence of mutations was highest (18.2%) in the uncommon histological subtypes followed by adenocarcinoma (AC, 7.3%) and adenosquamous carcinoma (ASC, 5.8%). During the median follow-up of 55 months, compared to patients with wild-type KRAS, a greater percentage of patients with mutant KRAS relapsed (20.0% vs. 42.9%, respectively, p=0.007). The 3-year relapse-free survival was poorer in patients with mutant KRAS than in patients without KRAS mutations (57.1% vs. 81.9%, respectively, p=0.001). Furthermore, the multivariate analysis showed that the presence of a KRAS mutation was an independent predictor for disease recurrence (hazard ratio [HR]=2.064; 95% confidence interval [CI]=1.125-3.787; p=0.019)., Conclusion: KRAS mutations were predominant in non-SCCs of the cervix and were associated with HPV 18 infection. A combination of KRAS mutation detection and HPV genotyping would be useful in identifying patient with poor prognosis for further interventions., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology)

Objective: This study sought to explore the outcomes and prognostic factors of patients with small cell neuroendocrine carcinoma of the cervix (SCNEC) and to determine the effects of adjuvant treatment on survival in patients with FIGO stage I-II SCNEC after radical surgery., Methods: A single-institution retrospective analysis was performed in 92 patients who underwent radical surgery for SCNEC. All clinicopathological variables and treatment strategies were reviewed. Kaplan-Meier and Cox regression methods were used for survival analyses., Results: During a median follow-up period of 38months (23.6-52.4), 43 (46.7%) patients experienced disease recurrence, and distant metastases were documented in 35 (81.4%) patients. The 3-year recurrence-free survival (RFS) for the entire group was 50.1%. The median RFS was 39months. The multivariate analysis confirmed that lymph node metastasis, positive parametrial extension and cycles of etoposide plus platinum (EP) were independent prognostic factors for disease recurrence. Adjuvant chemotherapy for at least 5cycles of EP (EP 5+, n=39) was associated with improved 5-year RFS compared with other treatments (n=46) (67.6% vs. 20.9%, p<0.001). Additional radiotherapy or concurrent chemoradiation failed to validate further improved RFS in patients with EP 5+, and this finding was consistent in the subset of patients with high-risk factors (positive lymph nodes or positive parametrium)., Conclusions: Half of stage I-II SCNEC patients experienced disease failure within 3years, and distant metastasis was an outstanding issue. EP regimen for at least 5cycles improved long-term RFS after radical surgery. Additional radiation might be unnecessary, even in patients with high-risk factors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the clinicopathological and prognostic relevance of PIK3CA mutations in Chinese patients with surgically resected cervical cancer. PIK3CA mutations were screened in 771 cervical cancer specimens using reverse transcription polymerase chain reaction and Sanger sequencing. In total, 13.6% (105 of 771) of patients harbored non-synonymous PIK3CA mutations. Patients harboring PIK3CA mutations were older than patients with wild-type PIK3CA (mean age: 50.7 years vs. 47.0 years, P < 0.01). PIK3CA mutations were more commonly observed in postmenopausal patients than in premenopausal patients (19.6% vs. 10.2%, P < 0.01). PIK3CA mutations were more common in squamous cell carcinomas than in non-squamous cell tumors (15.3% vs 7.3%, of P < 0.01). The 3-year relapse-free survival was 90.2% for PIK3CA mutant patients and 80.9% for PIK3CA wild-type patients (P = 0.03). PIK3CA mutation was confirmed as an independent predictor for better treatment outcome in the multivariate analyses (HR = 0.54, 95% CI: 0.29-0.99, P = 0.048). PIK3CA mutations were significantly associated with less distant metastases (mutant-type: 8/105, wild-type: 98/666, p = 0.048). Thus, patients with mutant PIK3CA had distinct characteristics in age, menopausal status, and histological subtype and have better treatment outcome and less distant metastasis after surgery-based multimodal therapy.

Mutations in 16 targetable oncogenic genes were examined using reverse transcription polymerase chain reaction (RT-PCR) and direct sequencing in 285 Chinese cervical cancers. Their clinicopathological relevance and prognostic significance was assessed. Ninety-two nonsynonymous somatic mutations were identified in 29.8% of the cancers. The mutation rates were as follows: PIK3CA (12.3%), KRAS (5.3%), HER2 (4.2%), FGFR3-TACC3 fusions (3.9%), PTEN (2.8%), FGFR2 (1.8%), FGFR3 (0.7%), NRAS (0.7%), HRAS (0.4%) and EGFR (0.4%). No mutations were detected in AKT1 or BRAF, and the fusions FGFR1-TACC1, EML4-ALK, CCDC6-RET and KIF5B-RET were not found in any of the cancers. RTK and RAS mutations were more common in non-squamous carcinomas than in squamous carcinomas (P=0.043 and P=0.042, respectively). RAS mutations were more common in young patients (<45 years) (13.7% vs. 7.7%, P=0.027). RTK mutations tended to be more common in young patients, whereas PIK3CA/PTEN/AKT mutations tended to be more common in old patients. RAS mutations were significantly associated with disease relapse. To our knowledge, this is the first comprehensive analysis of major targetable oncogenic mutations in a large cohort of cervical cancer cases. Our data reveal that a considerable proportion of patients with cervical cancers harbor known druggable mutations and might benefit from targeted therapy.

The aim of this study was to compare the amplification patterns of the human telomerase RNA gene (hTERC) in invasive cervical carcinomas (ICC) and cervical intraepithelial neoplasia grade III (CIN III) and to define their potential clinical implications. Cervical liquid-based cytological (LBC) specimens were collected from 53 squamous cell carcinomas (SCC), 14 CIN III, and 20 normal controls. Copy numbers of the hTERC gene were measured by fluorescence in situ hybridization (FISH) using a dual-color probe containing the hTERC probe and the control, chromosome 3 centromere-specific probe (CSP3). Nucleus with abnormal FISH pattern for hTERC was observed in 0.94-90.65% of SCC cells and in 0-85.59% of CIN III cells. Using the threshold of 5.89%, the occurrence of hTERC amplification in SCC and CIN III was similar (90.6% vs. 85.7%, P = 0.630). However, the median percentage of cells with extra gains of hTERC (hTERC:CSP3 > 1) in SCC was higher than in CIN III (64.3% vs. 31.7%, P = 0.001). Among those cells, the 3:2 signal pattern was the leading pattern for both SCC and CIN III; high-level amplification of hTERC was more common in SCC than in CIN III (60.9% vs. 48.9%, P = 0.002). In SCC, it was not found that extra gains of hTERC were associated with any clinicopathological parameters. Thus, hTERC amplification was common in cervical exfoliated cells from SCC and CIN III. More complex amplification patterns of hTERC were present in ICC. Clinical usefulness of hTERC amplification in LBC samples was limited in ICC., (Copyright © 2011 Wiley Periodicals, Inc.)