Potential Cervical Cancer Research Articles

Comprehensive analysis of clinical prognosis and biological significance of CNIH4 in cervical cancer.

Cornichon homolog 4 (CNIH4) belongs to the CNIH family. It functions as an oncogene in many tumors. However, CNIH4's significance in the immune landscape and its predictive potential in cervical cancer (CESC) is unexplored. CNIH4 levels and its effect on the survival of patients with CESC were evaluated using data retrieved from The Cancer Genome Atlas (TCGA). The oncogenic effect of CNIH4 in CESC was determined using small interfering RNA-mediated transfected cell lines and tumorigenesis experiments in animal models. Higher expression of CNIH4 was found in advanced tumor and pathological stages, as well as lymph node metastasis. CNIH4 expression correlated positively with the infiltration of macrophages M2 and resting dendritic cells into the affected tissue. Additionally, functional enrichment of RNA-sequencing of CNIH4-knocked down CESC cell lines showed the association of CNIH4 to the PI3K-Akt signaling pathway. Single-sample gene set enrichment analysis highlighted several immune pathways that were elevated in the CESC samples with enhanced levels of CNIH4, including Type-I and Type-II IFN-response pathways. The impact of CNIH4 on drug sensitivity was further assessed using the GDSC database. As CNIH4 is linked to the immune landscape in CESC, this study determined a four-gene risk prediction signature utilizing CNIH4-related immunomodulators. The risk score quantified from the prediction signature was an independent predictive indicator in CESC. Receiver operating characteristic curve analysis verified the good predictive ability of the four-gene signature in TCGA-CESC cohort. Thus, the CNIH4-related model showed potential as an auxiliary TNM staging system tool. CNIH4 may be an effective predictive biomarker for patients with cervical cancer, thus providing new ideas and research directions for CESC.

Ventriculography Modality in Detection and Evaluation of Cardiotoxicity in Breast Cancer Patients Receiving Chemotherapy

Background: Tumor-infiltrating lymphocytes (TILs), mainly CD4+ and CD8 + T cells, have been extensively described in anti-tumor immunity, and knowledge of CD4+ and CD8+ T lymphocytes’ interplay in mediating the control of tumor growth exists. We use the role of TILs in predicting the prognosis of cervical cancer patients and develop the discovery of new immunotherapy strategies that specifically target TILs.Methods: A systematic review of studies carried out a histopathological and immunohistochemical examination of TILs and an immunotherapy treatment.Results: 10 articles were selected for a systematic review. Expression of TILs was associated with the progression of NIS to cervical cancer. CD4+ and CD8+ TILs can determine the stage and prognosis of cervical cancer. TILs immunotherapy is effective for all cervical cancer patients. Combination chemotherapy with anti-TILs immunotherapy and combination therapy for PD-1 and TILs was found to have a better potential for cervical cancer therapy.Conclusions: TILs can be a prognostic biomarker and a marker to predict cervical cancer.

Cervical Cancer Risk Factors at Haji Adam Malik General Hospital Medan 2016-2018

The incidence of cervical cancer is still quite high. It is never separated from the risk factors that influence it. Some of them are sexually active, relatively young marital age, have high parity, use of contraception, and smoking can increase a woman's potential for cervical cancer. The aim of this study was to determine the characteristics of patients about the risk factors for cervical cancer in Haji Adam Malik General Hospital, Medan in 2016-2018. This research method uses descriptive observational design with cross sectional using medical record data. The results of this study using consecutive sampling techniques, took 100 samples and obtained several characteristics are age of patients, age of marriage, marriage history, number of parities, use of contraception, and smoking history. From this study it can be concluded that the characteristics of the incidence of cervical cancer in the General Hospital of Haji Adam Malik Medan in 2016-2018 are 50-59 years old, marital age ≤ 20 years old, married once, multigravida, uses injection type of hormonal contraception , and not smoking .

MiR-320c prevents the malignant development of cervical cancer by regulating GABRP level.

This study aims to explore the role of microRNA-320c (miR-320c) in regulating biological behaviors of cervical cancer and the potential mechanism, thus providing experimental references for developing therapeutic target of cervical cancer. Differential expressions of miR-320c in cervical cancer samples and normal cervical tissues were determined. Potential association between miR-320c level and clinical characteristics of cervical cancer patients was analyzed. After overexpression of miR-320c, migratory potential changes in HeLa, and C33-A cells were examined. At last, target gene binding to miR-320c was predicted online and its involvement in the malignant development of cervical cancer was finally explored. It was found that miR-320c was lowly expressed in cervical cancer tissues. Compared with cervical cancer patients with high expression of miR-320c, those with low expression had higher rates of lymphatic metastasis and distant metastasis. Besides, the overexpression of miR-320c markedly inhibited migratory potential in HeLa and C33-A cells. GABRP was verified to be the target gene binding to miR-320c. Notably, GABRP was able to reverse the role of miR-320c in regulating migratory potential in cervical cancer. MiR-320c is capable of inhibiting migratory potential in cervical cancer by targeting GABRP, which may be utilized as a therapeutic target of cervical cancer.

Protein-protein interactions of HPV-Chlamydia trachomatis-humanand their potential in cervical cancer.

Aim: HPVis an important cause of cervical cancer, but Chlamydia trachomatis (CT) is suspiciously involved in this disease ranging from direct to its involvement as a cofactor with HPV. We performed this study to understand the interaction of HPV and C.trachomatiswith humans and its contribution to cervical cancer. Materials & methods: Host-pathogen and pathogen-pathogen protein-protein interaction maps of HPV/CT/humanwere prepared and compared toanalyze interactions during single/coinfection of C. trachomatis and HPV. The interacting human proteins were detected by their involvement in cervical cancer. Results:C. trachomatis may interact with several cancer associated proteins while HPV and C. trachomatislargely interact with different human proteins, suggesting different pathogenesis. Conclusion:C. trachomatiscoinfection with HPV may modulate cervical cancer development.

Diagnostic value of heat shock protein 90α and squamous cell carcinoma antigen in detection of cervical cancer.

ObjectiveTo ascertain plasma levels of heat shock protein 90α (HSP90α) and squamous cell carcinoma antigen (SCC-Ag) and their diagnostic potential in cervical cancer.MethodsIn a cross-sectional study, patients’ cervical tissue samples were screened for high risk (HR) human papilloma virus (HPV) DNA and underwent a thinprep-liquid based cytology test (TCT). Plasma samples were analysed by enzyme-linked immunosorbent assay (ELISA) for HSP90 α and SCC-Ag levels.ResultsOf the 295 women who underwent screening, 75 were healthy controls 75 (HR-HPV−ve TCT−ve), 110 were HR-HPV+ve, TCT−ve and 110 were HR-HPV+ve TCT+ve. There were significant differences between levels of HSP90α and SCC-Ag proteins across the patient groups with those positive for cervical cancer having the greatest levels of proteins compared with other groups. For patients with high grade SCC there was a significant correlation between levels of HSP90α and SCC-Ag. The area under the ROC curve for combined HSP90α*SCC-Ag was the largest compared with the single proteins. Using a cut-off value of 16.4 ng/ml to delineate cervical cancer diagnosis, the sensitivity and specificity of HSP90α*SCC-Ag were 90.3% and 95.1% respectively.ConclusionPlasma HSP90α protein levels correlated well with SCC-Ag levels in patients with cervical cancer and the combination of HSP90α*SCC-Ag may be a useful diagnostic biomarker.

Flax seed oil reduced tumor growth, modulated immune responses and decreased HPV E6 and E7 oncoprotein expression in a murine model of ectopic cervical cancer

Cervical cancer is the second leading cause of cancer death in women in India. Previously, we have reported that alpha linolenic acid (ALA), induced apoptosis in cervical cancer cell lines and reduced expression of E6 and E7 oncoproteins with simultaneous decrease in Cox2/VEGF/MAP kinase proteins. Here, we investigated the tumor retardation potential of flax oil (FO), rich in ALA, in mouse papilloma model. Flax oil significantly reduced tumor volume and weight in mice compared to the Tumor control (TC) group. Interestingly, compared to cisplatin (Cis) alone, there was slightly enhanced decrease in tumor weight when FO was given together with Cis (Cis + FO). A marked increase in plasma antioxidant levels in mice, and increase in lipid peroxidation in tumors with simultaneous decrease in liver tissues was observed in Cis + FO group compared to either TC or Cis groups. FO and Cis + FO significantly modulated immune response in mice by increasing CD8α and IFNγ and decreasing IL-4 expression. Interestingly, when given together with cisplatin, flax oil reduced HPV E6 and E7 oncoprotein expression with concomitant increase in the relative mRNA expression of tumor suppressor genes p53 and Rb. Thus, flax oil could be explored for its therapeutic potential in cervical cancer.

Abstract 5855: Radiosensitization of cervical cancer cells by HDAC inhibitors

Abstract Introduction: While histone deacetylase (HDAC) inhibitors have demonstrated in vitro and in vivo radiosensitization in several human cancer cell lines, the efficacy and mechanism of action of HDAC inhibitors in HPV-positive cancers are poorly understood. We hypothesize that HDAC inhibitors can be used to treat HPV-positive squamous cell carcinomas by enhancing radiation sensitivity. Methods: The cellular cytotoxicity of ten HDAC inhibitors was examined in HPV-positive (CaSki, SiHa, HeLa) and HPV-negative (C33a) cervical cancer cell lines by the WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt] assay, and the drug with the highest cytotoxicity (pan-HDAC inhibitor SP-1-161) was selected for further analysis. SAHA was used as a control. Evaluation of the cell cycle phase distribution was performed by flow cytometry using FACS analysis following treatment with drugs at 24, 48, and 72 hours as well as in combination with radiation in CaSki cells (HPV-16 positive). The extent of radiation sensitization was confirmed by cellular clonogenic assays in CaSki cells. Results: Of all drugs tested, cytotoxicity was demonstrated in a dose-dependent manner. The values of IC50s were at 1.071, 1.567, 1.71, and 0.929 μM (SAHA) and 0.054, 0.3554, 0.0994, and 0.095 μM (SP-1-161) for CaSki, SiHa, HeLa, and C33a cell lines, respectively. SP-1-161 conferred significant cytotoxicity (0.054 μM) in CaSki cells. Cellular radiation sensitivity is tightly associated with cell cycle phases and varies as a function of the position in the cell cycle. To assess the effects of HDAC inhibitors on the cell cycle, CaSki cells were treated with IC50 dosage (SP-1-161 at 0.054 μM, SAHA at 1 μM) for 24 hours, 48 hours, and 72 hours and then treated with radiation. The drugs alone arrested cells primarily in the G1 phase of cell cycle (77.3% for SP-1-161, 84% for SAHA), a relatively radiation sensitive phase. Pre-treatment of SP-1-161 for 24 hours prior to radiation (5 Gy) increased cell cycle arrest in the G1 phase as well. To determine the radiosensitization property of SP-1-161, the radiation clonogenic survival assay was performed following pre-treatment of SP-1-161 for 24 hours. Cells were exposed to graded doses of γ-radiation, and the data were fitted using the single-hit multitarget and the linear-quadratic models. Comparisons of survival curves revealed smaller D0 (D0 ratio 1.43) for cells irradiated in the presence of SP-1-161 (D0 = 1.4) than for controls (D0 = 2.0). Interestingly, treatment with SAHA did not impact radiosensitization (D0 = 1.9, D0 ratio 1.05). Conclusion: SP-1-161 conferred significant toxicity in CaSki cells and primarily arrested cells in the G1 phase of cell cycle. Furthermore, treatment with SP-1-161 enhanced radiosensitization, while SAHA showed little change despite cell cycle arrest primarily in the G1 phase. Together, our results support SP-1-161 as a new therapeutic agent with potential for cervical cancer. Citation Format: Ima Paydar, Alfredo Velena, Scott Grindrod, Mira Jung. Radiosensitization of cervical cancer cells by HDAC inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5855. doi:10.1158/1538-7445.AM2017-5855

Anti-proliferative effect of novel primary cetyl alcohol derived sophorolipids against human cervical cancer cells HeLa.

Sophorolipids (SLs) are glycolipid biosurfactants that have been shown to display anticancer activity. In the present study, we report anti-proliferative studies on purified forms of novel SLs synthesized using cetyl alcohol as the substrate (referred as SLCA) and their anticancer mechanism in human cervical cancer cells. Antiproliferative effect of column purified SLCA fractions (A, B, C, D, E and F) was examined in panel of human cancer cell lines as well as primary cells. Among these fractions, SLCA B and C significantly inhibited the survival of HeLa and HCT 116 cells without affecting the viability of normal human umbilical vein endothelial cells (HUVEC). The two fractions were identified as cetyl alcohol sophorolipids with non-hydroxylated tail differing in the degree of acetylation on sophorose head group. At an IC50 concentration SLCA B (16.32 μg ml-1) and SLCA C (14.14 μg ml-1) blocked the cell cycle progression of HeLa cells at G1/S phase in time-dependent manner. Moreover, SLCA B and SLCA C induced apoptosis in HeLa cells through an increase in intracellular Ca2+ leading to depolarization of mitochondrial membrane potential and increase in the caspase-3, -8 and -9 activity. All these findings suggest that these SLCAs could be explored for their chemopreventive potential in cervical cancer.

MicroRNA-328 inhibits cervical cancer cell proliferation and tumorigenesis by targeting TCF7L2

microRNAs (miRNAs) play a vital role in tumor development and progression. In this study, we aimed to determine the expression and biological roles of miR-328 in cervical cancer and identify its direct target gene. Our data showed that miR-328 was significantly downregulated in human cervical cancer tissues and cells. Re-expression of miR-328 inhibited cervical cancer cell proliferation and colony formation in vitro and suppressed the growth of xenograft tumors in vivo. Bioinformatic analysis predicted TCF7L2 (an essential effector of canonical Wnt signaling) as a target gene of miR-328, which was confirmed by luciferase reporter assays. Enforced expression of miR-328 led to a decline in the expression of endogenous TCF7L2 in cervical cancer cells. In cervical cancer tissues, TCF7L2 protein levels were negatively correlated with miR-328 expression levels (r = −0.462, P = 0.017). Small interfering RNA-mediated knockdown of TCF7L2 significantly impaired the proliferation and colony formation of cervical cancer cells. Ectopic expression of a miRNA-resistant form of TCF7L2 significantly reversed the growth suppressive effects of miR-328 on cervical cancer cells, which was accompanied by induction of cyclin D1 expression. Taken together, our results provide first evidence for the growth suppressive activity of miR-328 in cervical cancer, which is largely ascribed to downregulation of TCF7L2. Restoration of miR-328 may have therapeutic potential in cervical cancer.

Poly(ADP-Ribose) Polymerase in Cervical Cancer Pathogenesis: Mechanism and Potential Role for PARP Inhibitors

Treatment options for disease recurrence of women treated for locally advanced and advanced cervical cancer are very limited-largely palliative chemotherapy. The low efficacy of the currently available drugs raises the need for new targeted agents. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) have emerged as a promising class of chemotherapeutic agents in cancers associated with defects in DNA repair. Their therapeutic potential in cervical cancer is currently being evaluated in 3 ongoing clinical trials. Here we review the available information regarding all the aspects of PARP in cervical intraepithelial neoplasia and invasive cervical cancer, from expression and the mechanism of action to the role of the polymorphisms in the pathogenesis of the disease, as well as the potential of the inhibitors. We finally propose a new unifying theory regarding the role of PARPs in the development of cervical carcinomas.

Alpha-linolenic acid regulates Cox2/VEGF/MAP kinase pathway and decreases the expression of HPV oncoproteins E6/E7 through restoration of p53 and Rb expression in human cervical cancer cell lines.

Cervical cancer represents the largest cause of mortality in women worldwide. In our previous report, we have shown how alpha-linolenic acid (ALA), an omega-3 fatty acid, regulated the growth of cervical cancer cells. The present study aimed to explore mechanistic details for the anticancer activity of ALA in cervical cancer cell lines, SiHa and HeLa. ALA significantly modulated the growth kinetics of the cells and reduced cell migration with concomitant decrease in the expression of VEGF, MMP-2, and MMP-9 proteins. Besides this, ALA significantly decreased the expression of phosphorylated p38, pERK1/2, c-JUN, NFκB, and COX2, proteins. Most importantly, ALA reduced the expression of HPV onco-proteins E6 and E7, resulting into restoration of expression of tumor suppressor proteins, p53 and Rb. These results suggested that ALA could be explored for its therapeutic potential in cervical cancer.

Correlation of Twist and YB-1 up-regulation and epithelial-mesenchymal transition during tumorigenesis and progression of cervical carcinoma

To investigate the clinicopathological significance of Twist and YB-1 up-regulation in cervical cancer, and to correlate the expression of the two genes with E-cadherin, a marker of epithelial-mesenchymal transition (EMT). A total of 202 tissue samples were collected during January 2008 to December 2013, including 50 cases of normal cervical tissues, 100 cases of cervical intraepithelial neoplasia (CIN) and 52 cases of squamous cell carcinoma (SCC). Twist, YB-1 and E-cadherin expression was investigated by MaxVision. Increased expression levels of Twist and YB-1 were found and correlated with the malignant transformation of cervical epithelium, histological progression and metastasis of cervical cancer. In addition, Twist and YB-1 overexpression was also associated with aberrant expression of E-cadherin. Regression analysis revealed that Twist expression was an independent factor for the histological progression of cervical cancer. It is suggested that Twist and YB-1 overexpression is significantly linked to cervical cancer tumorigenesis and progression, likely related to EMT through (YB-1)-Twist-(E-cadherin) pathway. Twist and YB-1 may be markers for determining the metastatic potential of cervical cancer.

The aqueous extract of Ficus religiosa induces cell cycle arrest in human cervical cancer cell lines SiHa (HPV-16 Positive) and apoptosis in HeLa (HPV-18 positive).

Natural products are being extensively explored for their potential to prevent as well as treat cancer due to their ability to target multiple molecular pathways. Ficus religiosa has been shown to exert diverse biological activities including apoptosis in breast cancer cell lines. In the present study, we report the anti-neoplastic potential of aqueous extract of F. religiosa (FRaq) bark in human cervical cancer cell lines, SiHa and HeLa. FRaq altered the growth kinetics of SiHa (HPV-16 positive) and HeLa (HPV-18 positive) cells in a dose-dependent manner. It blocked the cell cycle progression at G1/S phase in SiHa that was characterized by an increase in the expression of p53, p21 and pRb proteins with a simultaneous decrease in the expression of phospho Rb (ppRb) protein. On the other hand, in HeLa, FRaq induced apoptosis through an increase in intracellular Ca2+ leading to loss of mitochondrial membrane potential, release of cytochrome-c and increase in the expression of caspase-3. Moreover, FRaq reduced the migration as well as invasion capability of both the cervical cancer cell lines accompanied with downregulation of MMP-2 and Her-2 expression. Interestingly, FRaq reduced the expression of viral oncoproteins E6 and E7 in both the cervical cancer cell lines. All these data suggest that F. religiosa could be explored for its chemopreventive potential in cervical cancer.

Immunohistochemical assessment of the growth fraction in cervical cancers using the monoclonal antibody Ki-67; relationship to the clinical stage, histologic type and DNA content.

To assess the growth potential of cervical cancer, cell populations in proliferating cycle (%PC) were examined by an immunohistochemical technique using the monoclonal antibody Ki-67. The %PC was 31.63 +/- 16.61% in 36 cervical cancers and was significantly higher when compared to the 7.8 +/- 3.81% found in 24 samples of normal ectocervical tissues. In cervical cancer tissues, the %PC increased in accordance with progression of the clinical stage of the disease, however, the %PC was not different among the various histologic types of invasive cervical cancers. The DNA index also increased in accordance with progression of the clinical stage of cervical cancer, however, there was no correlation between the %PC and the DNA index. These results suggest that the value of %PC obtained using the monoclonal antibody Ki-67 can be used as a parameter for evaluating the growth activity of cervical cancer and for predicting biological heterogeneity in a tumor.

Generation of Mucosal Vaccine Utilizing Lactobacillus Display System

Lactic acid bacteria (LAB) are a group of Gram-positive, and generally recognized as safe bacteria. LAB have been used as the starter for the fermentation food (i.e., cheese, yoghurt and kimuchi etc.). On the other hand, several studies of LAB as delivery vehicles have focused on the generation of mucosal vaccine. We have developed novel surface display system based on PgsA gene, which isolated from Bacillus subtilis chungkookjang. We introduce the Lactobacillus surface display system by using the PgsA anchor protein and its application. HPV oncogene, E7, is a reliable target protein since E7 is expressed in the CIN lesion. Although many studies have demonstrated these vaccines elicit systemic immune responses to HPV E6/E7, few studies have shown mucosal immune responses. There is no therapeutic vaccine utilizing oral administration and there is no clinical trial which addresses cervical mucosal cellular immune responses to the vaccine. Our recent progress is production of a mucosal vaccine to treat cervical intraepithelial neoplasia (CIN) that has potential of cervical cancer. The vaccine is expected to help the vast number of women suffering from high grade CIN. Lac-E7 is a candidate for new therapeutic vaccine for cervical intraepithelial neoplasia.

Women’s health—what’s new world wide

Women’s health—what’s new world wide

Growth inhibitory effects and radiosensitization induced by fatty aromatic acids on human cervical cancer cells.

Evidences have been reported that phenylacetic (PA) and phenylbutyric (PB) fatty aromatic acids can exert tumor growth inhibition in vitro and in vivo. Moreover, clinical trials also showed some activity for these drugs to modulate the expression of genes implicated in tumor growth, metastasis, immunogenicity, and to potentiate the efficacy of cytotoxic agents. The aim of the study was to examine the effects of PA and PB on the growth as well as sensitization to cisplatin and radiation in human cervical cancer cells. The effects of PA and PB on the proliferative activity and apoptosis induction in cervical tumor tissue was investigated. Both PA and PB exhibited a time- and dose-dependent antiproliferative activity in SW756 and ME180 cell lines: after 72-h treatment, the IC50 (concentration able to inhibit 50% of cell growth) of PB was 1.9 +/- 0.2 mM and 1.5 +/- 0.2 mM in SW756 and ME180 cells, respectively, while the IC50 of PA was 13.0 +/- 1.7 mM and 10.0 +/- 1.2 mM in SW756 and ME180 cells, respectively. In tumor tissue biopsies obtained from patients affected by squamous cervical cancer, both drugs resulted in a marked reduction of the percentage of bromodeoxyuridine-labeled cells compared with untreated samples [19.0 +/- 1.63% in untreated tissues with respect to 1.30 +/- 0.54% and 4.20 +/- 2.50% of stained cells after treatment with PA (30 mM) (P < 0.0001) and PB (5 mM) (P < 0.0001), respectively]. Moreover, analysis of the staining with M30 monoclonal antibody revealed that PA (30 mM) and PB (5 mM) were able to produce a marked increase in the number of stained apoptotic nuclei with respect to untreated samples. Finally, PB and PA were shown to enhance the sensitivity of SW756 to radiation and to exert an additive effect when combined with cisplatin. A significant reduction of the processed form of p21ras and rhoB proteins in the membrane fraction of cells exposed to PA and PB was observed. When farnesol, which is able to circumvent the enzymatic step inhibited by PA and PB, was added to the medium only a partial reversal of the growth inhibition and potentiation of sensitivity to radiation induced by PA and PB were found. In conclusion, the growth inhibitory properties of fatty aromatic acids suggest that these molecules could represent the prototype of a new class of compounds with some therapeutic potential in cervical cancer.

Age-related differences and changes in clinical aspects and follow-up of cervix cancer since 1973

In an attempt to clarify, whether the malignant potential of cervical cancer is age-dependent and whether this has changed in the last decade, we analysed the data from 1496 patients suffering from cervical cancer. The patients were treated between 1973 and 1988 at the second Universitäts-Frauenklinik, Lindwurmstrasse and at the Frauenklinik Grosshadern, both of the Ludwig-Maximilians-Universität München. After 1973, the total number of patients with cervical cancer decreased, whilst at the same time, the percentage of young patients increased. In the sub-group of surgically treated patients (n = 555), the percentage of patients with lymph node metastases increased after 1973. The increase in lymph node involvement was most pronounced in young patients with small tumours (stage Ib disease, 35 years of age). In this group, the percentage of lymph node involvement rose from 6.3% in 1973 to 38.6% in 1988. Lower stage disease was significantly more frequent in the young patients. Accordingly, the overall mean survival time was longer in the young patients. In the sub-group of surgically treated patients, however, when comparing equal stages, the survival time was shorter in the young patients. In small tumours (confined to the uterine cervix), pelvic lymph node involvement was more frequently seen in the younger patients. Secondary metastases developed more rapidly and significantly more often in the young patients. Our data supply evidence to indicate an enhanced malignancy of cervical cancer in young patients.