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PubMed1999

Prevalence of self-reported cervical cancer screening and impact on cervical cancer mortality in Austria.

Pap smear screening was introduced in Austria in the late 1960's and was recommended annually for all women older than 20 years ever since. This is an opportunistic screening. The evaluation has to rely on population based data (mortality, stage distribution, screening prevalence). In a representative cross-sectional study (women aged 20-69 years, n = 933, conducted in 1995), 76% reported at least one Pap screening during their life; the highest prevalence (88%) was reported by women aged 50-59 years, the lowest prevalence (65%) by women aged 60-69 years. Forty-eight per cent of all women reported that they had undergone screening at least 4 times (40-49 years: 57%, 20-29 years: 34%). Between 1980 and 1996, mortality due to cancer of the uterus, part unspecified (ICD-9: 179), decreased by 54% (P = 0.0001) and that of cancer of the cervix (ICD-9: 180) by 44% (P = 0.0001). Since 1980, age-specific incidence rates of invasive disease decreased (P = 0.0001) in all 10-year age groups (20-29 years: -59%, 30-39 years: -48%, 40-49 years: -34%, 50-59 years: -62%, 60-69 years: -59%). The incidence of preinvasive disease increased significantly (P = 0.001) in the age groups 20-29 years by 30% and 30-39 years by 45%, respectively. No significant changes are observed in other age groups. Opportunistic screening has reduced mortality from cervical cancer and particularly limited the increase among younger women, but the high proportion of cancer deaths from uterine cancer, in part unspecified, obscures the actual trend. We estimate that the true mortality from cervical cancer has been nearly halved between 1980 and 1996. Most of this reduction must be attributed to the screening activities in the 1970's and we expect a further decrease as a result of the expanded screening activities in the 1980's.

Adult↗
PubMed2006

Semi-quantitative fluorescent PCR analysis identifies PRKAA1 on chromosome 5 as a potential candidate cancer gene of cervical cancer.

OBJECTIVE: Comparative genomic hybridization has frequently detected amplification of chromosome 5p in cervical cancer, but candidate cancer genes within the region are rarely known. Therefore, we pursued to identify potential candidate gene related to cervical cancer development. METHODS: A series of 128 cervical tumor samples were examined by semi-quantitative fluorescent differential PCR for copy number changes on three candidate genes (PRKAA1, CTNND2 and POLS) mapped to chromosome 5p and one gene (ERBIN) mapped to chromosome 5q12.3. The impact of gene copy number was later analyzed in relation to HPV infection, tumor stage or tumor radiosensitivity. RESULTS: DNA copy numbers of PRKAA1, CTNND2 and ERBIN were significantly different from normal controls (P < 0.05). DNA copy number changes did not correlate with HPV infection, tumor stages or tumor radiosensitivity. Using RT-PCR, PRKAA1 mRNA expression in seven tumor samples with known 5p amplification was amplified from 3- to 15-fold. Over-expression of PRKAA1 was further confirmed by immunohistochemical staining on 125 paraffin-embedded cervical cancer tissues. The expression level in cervical tumor was significantly higher than that in normal epithelium (P < 0.001). CONCLUSIONS: PRKAA1 gene codes for the catalytic alpha 1 subunit of the AMP-activated protein kinase which is an important cellular metabolic stress regulator. It might assist tumor cells growth under stress. Thus, PRKAA1 may be one of the potential candidate genes for cervical carcinogenesis.

AMP-Activated Protein Kinases↗
PubMed2002

Telomerase--a potential molecular marker of lung and cervical cancer.

Telomerase, a ribonucleoprotein enzyme that adds hexameric TTAGGG nucleotide repeats onto telomeres is reactivated in most malignancies. Lung cancer is a common malignant disease worldwide as well as in India. Most patients present in advanced stages. As noninvasive diagnostic techniques are preferred, we assayed the telomerase activity in pre-bronchoscopy sputum and compared it with that of bronchial washings and bronchoscopic biopsies by telomeric repeat amplification protocol (TRAP) in 53 cases of lung cancer. These were corroborated with cytopathological/histopathological examinations. Telomerase activity was detected in 58.5% of sputum samples, 70% of bronchial washings and 74% of bronchoscopic biopsies thereby making it a good noninvasive diagnostic marker of lung cancer. Cervical cancer is the 7th most common cancer worldwide, with 100,000 new cases being reported annually in India. It is routinely screened by Papanicolaou's (Pap) smear. Human papilloma virus (HPV) is one of its etiological agents. We have assayed telomerase activity in relation to HPV-16/18 in cervical samples from 93 subjects ranging from normal to precancerous to frank cancers in tissue biopsies and cervical scrapings. HPV infection was detected by polymerase chain reaction (PCR) in 81% of tumor samples, in 6% of control hysterectomy samples and in 2% of cervical scrapings of normal healthy controls with HPV-16 being the predominant type. Telomerase activity was detected in 96.5% of cervical tumor samples, in 68.7% of premalignant cervical scrapings but was not detected in control hysterectomy samples, or in cervical scrapings of normal healthy controls. There was 71% correlation between telomerase activity and HPV-16/18 infection.

Adult↗
PubMedDate not supplied

Special problems in cervical cancer management.

Cervical cancer is easily recognized when it presents as a visible lesion, but a problem arises when it adopts unusual presentations. Cervical cancer can develop high in the endocervical canal, beyond the reach of cone biopsy. Copious vaginal discharge from cervical adenocarcinoma may lead to a false-negative Papanicolaou (Pap) smear. Treatment of cervicitis can result in a delay in diagnosis. Successful and timely diagnosis and treatment of cervical cancer requires experience and vigilance. Careful intraoperative palpation of the cervix and uterus can help determine the location and extent of the lesion. Flexibility during surgery is required to utilize intraoperative findings and thus optimize treatment. Pitfalls of cervical cancer diagnosis and treatment with actual case presentations are presented along with other special problems in cervical cancer management such as incidental findings of cervical cancer in hysterectomy specimens, treatment of cervical stump cancers, and unusual cervical cancer cell types.

Adenocarcinoma↗
PubMed2005

Integrated human papillomavirus types 52 and 58 are infrequently found in cervical cancer, and high viral loads predict risk of cervical cancer.

OBJECTIVE: The aim of this prospective study was to analyze whether integration or high viral loads of human papillomavirus (HPV) is essential for malignant transformation of HPV types 52 and 58 as well as types 16 and 18. METHODS: Cervical swabs from 178 consecutive patients, including 81 with invasive cervical cancers and 97 with cervical intraepithelial neoplasias (CIN) II-III, were collected and examined to determine the physical status and viral load of HPV types 16, 18, 52 and 58 DNA using genechip and real-time PCR (polymerase chain reaction) analysis. RESULTS: In cervical cancer patients, the integrated form of HPV 52 and 58 DNA was found in 25.0% and 12.5% of swabs, respectively; while HPV16 and 18 DNA was found in 82.6% and 100% of swabs, respectively (P < 0.01, for pair-wise comparison of types 16, 18 versus types 52, 58). The viral loads reflected by the amount of E6 for HPV 16, 18, or 52 were significantly increased in invasive cervical cancer compared to CINII-III (P = 0.022 for type 16, P = 0.003 for type18, and P = 0.001 for type 52, respectively). Area under the receiver operating characteristic (ROC) curve for cervical cancer versus CIN II-III was 73.8%, 92.9%, and 88.5% for HPV 16, 18, and 52, respectively, indicating that real-time PCR had good diagnostic value in differentiating cervical cancer from CIN II-III. CONCLUSIONS: Infrequent integration of HPV 52 and 58 DNA in cervical cancer suggests that it is not prerequisite for progression to cervical cancer. High viral loads (E6) of HPV 16, 18, and 52 DNA may be predictive of the transition of CIN II-III to cervical cancer. Our results indicate that both viral DNA physical status and viral loads of HPV are important factors in the carcinogenesis of different HPV types.

DNA, Viral↗
PubMed1999

Analysis of referral initiatives, severity of illness and return to care of older women with cervical cancer.

BACKGROUND: Cervical cancer is a worldwide malignancy particularly prevalent in older women. Due to the increasing population ratio of older women and their more complicated illnesses, doctors in Taiwan are concerned about the care of older patients with cervical cancer. Few studies have been performed on the association between referral initiative and illness severity upon referral as well as the tendency of older patients with cervical cancer to return to the referring doctor and to the consultant at the medical center for follow-up. The purpose of this study was to investigate the referral association by adjusting for confounding variables. METHODS: This study included 214 women aged 65 years and over with cervical cancer diagnosed between 1987 and 1995. Patients were referred to a tertiary teaching hospital by 71 primary care gynecologists. The International Federation of Gynecology and Obstetrics clinical stage and clinical severity were assessed in each patient. Histopathologic results were reviewed to confirm the diagnosis. RESULTS: Of all the cervical cancer referrals, 20.2% were initiated by patients or families and 79.8% were initiated by primary care doctors. No statistically significant differences were found in the Basic Activities of Daily Living or Instrumental Activities of Daily Living between doctor- and patient-initiated referrals. High Geriatric Depression Scale and low Mini-Mental State Examination were associated with doctor-initiated referrals. Higher cancer stage and greater clinical severity of patients with cervical cancer was found in patient- rather than doctor-initiated referrals. After adjusting for marriage, family type, medical payment, mental status, cancer stage and clinical severity, the data showed that, if the referral was initiated by a primary care doctor, older patients with cervical cancer had a similar likelihood to return to both the primary care doctor and the tertiary teaching hospital for follow-up. CONCLUSIONS: If a referral was initiated by a doctor, older women with cervical cancer were not only likely to return to their consulting physician at the medical center, but also likely to return to their primary care doctor. Continuous care is more likely to occur when the primary care doctor initiated the referral.

Aged↗
PubMed2007

Screening history of women in Malmö with invasive cervical cancer.

OBJECTIVES: Cervical cancer is one of the most common forms of cancer among women. Cytological screening and follow-up are potentially effective procedures for preventing the development of - and mortality from - cervical cancer. The purpose of this study was to investigate the screening history of women diagnosed with cervical cancer with the aim of improving the screening programme. STUDY DESIGN: All of the 187 women diagnosed with invasive cervical cancer in Malmö between 1991 and 2000 were identified, and those below 61 years of age (n=130) were included in the analysis. The cytological and histological screening history of these women prior to their diagnosis was scrutinized. We analyzed shortcomings related to the cervical screening with special attention to participation defined as having had a cervical smear within 1 year of the scheduled time. RESULTS: Of the non-participants who developed cervical cancer (n=70), roughly one-third "never participated," half were "sub-optimal participants," and one-sixth were "decliners," i.e., women who declined the recommended measures. Among participants (n=60), 80% were either "unexplained" (n=35) or "misread as normal" (n=13). The 9.5% subgroup of non-participants was at an 11-fold increased risk of being diagnosed with invasive cervical cancer. CONCLUSION: The greatest reduction in cervical cancer would be realized if non-participants could be brought into the screening program.

Adult↗
PubMed2026

AGRN activates GPX4 via the Wnt/beta-catenin signaling pathway to suppress ferroptosis in cervical cancer cells.

Cervical cancer remains a leading cause of cancer-related deaths among women worldwide. Targeting ferroptosis, a regulated form of cell death driven by lipid peroxidation, has emerged as a promising therapeutic strategy. This study aimed to elucidate the mechanisms by which cervical cancer cells acquire resistance to ferroptosis. AGRN expression and its prognostic significance were analyzed in cervical cancer using TCGA and GTEx data. In vitro, AGRN levels were measured in HeLa, CaSki, and Ect1/E6E7 cells via qRT-PCR. mRNA and protein expression levels of AGRN, beta-catenin, and ferroptosis-related markers were evaluated by qRT-PCR and western blot (WB). Cell viability, RSL3 sensitivity (IC50), and lipid ROS were assessed via CCK-8 assay and flow cytometry. In a xenograft model, RSL3's effect on tumor growth was examined. Immunohistochemistry (IHC) and molecular analyses (qRT-PCR, WB, and flow cytometry) were performed on tumor tissues to evaluate AGRN, beta-catenin, Ki-67, ferroptosis-related genes, and lipid ROS. It is found through research that, AGRN was significantly upregulated in cervical cancer tissues and cell lines. Its overexpression activated Wnt/beta-catenin signaling, resulting in elevated GPX4 and SLC7A11 levels and reduced CHAC1 and PTGS2 expression levels. These alterations decreased lipid ROS accumulation and enhanced resistance to RSL3-induced ferroptosis, an effect further confirmed in xenograft models. In short, In short, AGRN promotes ferroptosis resistance in cervical cancer by activating the Wnt/beta-catenin signaling pathway and upregulating GPX4 expression. Targeting the AGRN-Wnt/beta-catenin-GPX4 axis may represent a novel therapeutic approach for cervical cancer.

Humans↗
PubMed2002

Concurrent chemoradiotherapy in cervical cancer (a new paradigm in cervical cancer treatment).

During the last century, the mainstay for the treatment of uterine cervix cancer has been via two main primary treatment modalities, these being radical surgery (radical hysterectomy and regional lymph nodes dissection) and radiotherapy. Generally, radical surgery is restricted to stages I and IIa of FIGO (the International Federation of Gynecology and Obstetrics) Classification, while radiotherapy may be applied to all stages of cervical cancer. In 1999 the National Cancer Institute Clinical Announcement established concurrent chemoradiotherapy as a new primary treatment modality, which is the focus of this review.

Combined Modality Therapy↗
PubMed1996

The causal link between HPV and cervical cancer and its implications for prevention of cervical cancer.

This article reviews epidemiologic evidence linking human papillomavirus (HPV) to cervical cancer. The authors conclude that over 90% of all cervical cancers can be attributed to certain HPV types-HPV 16 accounting for the largest proportion (roughly 50%) followed by HPV 18 (12%), HPV 45 (8%), and HPV 31 (5%). Recognition of this circumstance has far-reaching implications for primary and secondary prevention of this malignancy. At present, prophylactic and therapeutic HPV vaccines are under development, and HPV typing is being integrated into pilot study screening programs in a few developed countries. In developing countries, well conducted conventional screening programs remain the best approach for the control of cervical cancer until a safe and efficient HPV vaccine can be developed for use by the general population.

Adenocarcinoma↗
PubMed1995

Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group.

BACKGROUND: Epidemiologic studies have shown that the association of genital human papillomavirus (HPV) with cervical cancer is strong, independent of other risk factors, and consistent in several countries. There are more than 20 different cancer-associated HPV types, but little is known about their geographic variation. PURPOSE: Our aim was to determine whether the association between HPV infection and cervical cancer is consistent worldwide and to investigate geographic variation in the distribution of HPV types. METHODS: More than 1000 specimens from sequential patients with invasive cervical cancer were collected and stored frozen at 32 hospitals in 22 countries. Slides from all patients were submitted for central histologic review to confirm the diagnosis and to assess histologic characteristics. We used polymerase chain reaction-based assays capable of detecting more than 25 different HPV types. A generalized linear Poisson model was fitted to the data on viral type and geographic region to assess geographic heterogeneity. RESULTS: HPV DNA was detected in 93% of the tumors, with no significant variation in HPV positivity among countries. HPV 16 was present in 50% of the specimens, HPV 18 in 14%, HPV 45 in 8%, and HPV 31 in 5%. HPV 16 was the predominant type in all countries except Indonesia, where HPV 18 was more common. There was significant geographic variation in the prevalence of some less common virus types. A clustering of HPV 45 was apparent in western Africa, while HPV 39 and HPV 59 were almost entirely confined to Central and South America. In squamous cell tumors, HPV 16 predominated (51% of such specimens), but HPV 18 predominated in adenocarcinomas (56% of such tumors) and adenosquamous tumors (39% of such tumors). CONCLUSIONS: Our results confirm the role of genital HPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide. They also suggest that most genital HPVs are associated with cancer, at least occasionally. IMPLICATION: The demonstration that more than 20 different genital HPV types are associated with cervical cancer has important implications for cervical cancer-prevention strategies that include the development of vaccines targeted to genital HPVs.

Adult↗
PubMedDate not supplied

Cervical intraepithelial lesions and cervical cancer among Asian Pacific Islander women in a cervical cancer screening program.

Utilizing data from a cervical cancer screening program in California, we examined the relationship between being a woman of Asian/Pacific Islander (API) origin and receiving different types of abnormal cervical diagnoses. Initial descriptive data reflected a higher than expected percentage of API subjects with a final diagnosis of in situ and invasive cervical cancer when compared with other subjects in other ethnic groups (N = 2792). Results of multivariate analysis indicated that being of API origin retained significance in a model explaining the level of severity of the cervical final diagnosis, even when controlling for other significant predictors such as having a prior pap smear, age, referral source, the presence of cervical abnormalities and the time from screening to diagnosis. We conclude that women of API origin may not be accessing health care sufficiently early to prevent increasingly severe final diagnoses. Utilizing data from a cervical cancer screening program in California, we examined the relationship between being a woman of Asian/Pacific Islander (API) origin and receiving different types of abnormal cervical diagnoses. Initial descriptive data reflected a higher than expected percentage of API subjects with a final diagnosis of in situ and invasive cervical cancer when compared with other subjects in other ethnic groups (N = 2792). Results of multivariate analysis indicated that being of API origin retained significance in a model explaining the level of severity of the cervical final diagnosis, even when controlling for other significant predictors such as having a prior pap smear, age, referral source, the presence of cervical abnormalities and the time from screening to diagnosis. We conclude that women of API origin may not be accessing health care sufficiently early to prevent increasingly severe final diagnoses.

Adult↗
PubMed2004

CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients.

Cervical cancer is the principal cause of death due to cancer in women. Five-year survival rate ranges from 15-80%, depending on the extent of the disease. New predictive markers for relapse may increase survival rates by improving treatment of patients at high risk for relapse. The gene products of CDH1 and CDH13, namely E-cadherin and H-cadherin, play a key role in cell-cell adhesion. Inactivation of the cadherin-mediated cell adhesion system, caused by aberrant methylation, is a common finding in human cancers. To test the hypothesis that CDH1/CDH13 methylation is a prognostic marker in cervical cancer we determined the methylation status of CDH1/CDH13 in serum samples from 93 cervical cancer patients. Methylation analysis was carried out using MethyLight. Aberrant methylation of the 5'-region of CDH1 or CDH13 was observed in 43% (40 of 93) of the patients. Cervical cancer patients with unmethylated CDH1/CDH13 in serum samples showed significantly better disease-free survival in univariate and multivariate analysis. Median disease-free survival for CDH1/CDH13 methylation negative and positive patients was 4.3 years and 1.2 years, respectively. Our results suggest that detection of aberrant methylation of CDH1/CDH13 may be of potential use as a marker for selecting cervical cancer patients at high risk for relapse who could benefit from additional systemic therapy.

Adult↗
PubMedDate not supplied

[Dilemmas in the surgical treatment of cervical cancer].

INTRODUCTION: Cervical cancer is the second most common cancer of the female genital tract. There are 2200 newly registered cases of cervical cancer each year in Serbia, out of which 650 women die. The incidence of invasive, advanced cervical cancer has been on decrease, whereas the incidence of "in situ" stage carcinoma increases by 2% per year with tendency of increase in the younger age groups. HISTORICAL DATA: The first radical abdominal hysterectomy was performed by Ernst Wertheim from Wienna in 1898, whereas Schauta performed the first vaginal hysterectomy in 1902. It was in 1995 when Daniel Dargent introduced radical vaginal trachelectomy combined with laparoscopic lymphadenectomy in order to preserve fertility in cases of initial-invasive stages of cervical cancer (FIGO I A2, I B1). CHOICE OF SURGICAL PROCEDURE: Before choosing the surgical procedure, it is necessary to make a correct preoperative estimation of the stage of disease according to FIGO classification. Apart from gynecologic and rectovaginal examinations, in some cases it is necessary to perform additional examinations such as: cystoscopy, rectoscopy, CT or MRI examination of the pelvis, IVU, chest X-ray etc. The decision can be made only by an experienced gynecologist-surgeon who is able to solve all complications of treatment by himself. CONCLUSION: There are different surgical procedures for cervical cancer: abdominal, vaginal and combined. Introduction of laparoscopic lymphadenectomy combined with vaginal radical operations, to decrease surgical trauma and preserve fertility, has been of great significance.

Female↗
PubMedDate not supplied

Cervical cancer screening and demonstration projects to identify barriers to preventing cervical cancer mortality.

Cervical cancer screening and demonstration projects to identify barriers to optimal screening are discussed. Interview surveys showed that older women and women in low-income groups tended to have lower rates of Papanicolaou smear screening. Data produced by demonstration projects established by the Centers for Disease Control in collaboration with state and local authorities and private institutions will be used to design and implement strategies for increasing screening levels to further reduce cervical cancer mortality.

Age Factors↗