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PubMed2003

Selection of HER-2/neu-positive tumor cells in early stage cervical cancer: implications for Herceptin-mediated therapy.

OBJECTIVE: The purpose of this study was to compare HER-2/neu expression on biopsies obtained from early stage cervical cancer, primary cell lines established therefrom, established cervical cancer cell lines, and metastatic or recurrent sites of disease; and to evaluate the sensitivity of primary cervical cancer cell lines to treatment with a humanized MAb against HER-2/neu (Herceptin). METHODS: Surface HER-2/neu expression on 18 cervical cancer cell lines was compared to HER-2/neu detection by immunohistochemistry on biopsies obtained from the original tumors (10 patients) and sites of recurrence (2 patients). Primary cell lines were tested for sensitivity to Herceptin-mediated antibody-dependent cellular cytotoxicity (ADCC) and sensitivity to Herceptin-mediated inhibition of proliferation. RESULTS: Nine out of 10 primary (90%) and 8 out of 8 (100%) established cervical cancer cell lines expressed HER-2/neu by flow cytometry. Surprisingly, all HER-2/neu-positive primary cell lines were derived from tumor biopsies that scored negative (i.e., 0 to 1+) for HER-2/neu expression by immunohistochemistry. Heavy staining for HER-2/neu (i.e., 3+) was found in the recurrent/metastatic lesions of the two relapsed patients. Importantly, all HER-2/neu-positive primary cell lines were highly sensitive to Herceptin-mediated ADCC, and their proliferation was also significantly inhibited by Herceptin. A significant enhancement of Herceptin-mediated ADCC was demonstrated when effector cells were exposed to low doses of IL-2 in vitro. CONCLUSIONS: Early stage cervical cancer may develop a population of HER-2/neu-positive cells with a selective growth advantage over HER-2/neu-negative cells. Therapy which targets HER-2/neu may be more effective in patients with cervical cancer than indicated by the commonly low expression of HER-2/neu in tumors removed at the time of primary treatment.

Adult↗
PubMed2004

Beliefs about the risk factors for cervical cancer in a British population sample.

BACKGROUND: The introduction of human papillomavirus (HPV) testing into cervical screening has the potential to alter public perceptions of cervical cancer by making explicit the role of a sexually transmitted virus in its etiology. HPV knowledge has been found to be poor, although there is evidence of public awareness of a link between sexual activity and cervical cancer risk. We explored beliefs about the risk factors for cervical cancer in a large population sample. METHODS: Face-to-face interviews were carried out with a representative sample of the British population. All participants were asked what they thought increased a women's chances of developing cervical cancer. RESULTS: The response rate was 71% (n = 1940). The most common single response was 'don't know' (38%). Forty-one percent of respondents mentioned factors relating to sex, but only 14% were aware of a link with sexual transmission and fewer than 1% named HPV. Women and more educated people had better knowledge of the established risk factors. The patterning of risk factor awareness by age varied across risk factors. CONCLUSIONS: Awareness of the role of a sexually transmitted virus in the etiology of cervical cancer is very low in Britain. Provision of information associated with the introduction of HPV testing could change public perceptions of cervical cancer.

Adolescent↗
PubMed1993

Serologic response in human papillomavirus-associated invasive cervical cancer.

Human papillomavirus (HPV) transforming proteins E6 and E7 are uniformly expressed in HPV-associated cervical cancer. Our objective was to measure antibodies to HPV-16 E6 and E7 proteins in cervical cancer patients using an assay which would detect antibodies to conformational epitopes. Serum specimens obtained from two case-control studies of HPVs and cervical cancer were tested. The studies were performed in Cali, Colombia, South America and in 9 provinces of Spain. Cases consisted of women with invasive cervical cancer associated with HPV-16 or other HPV types and women with HPV-16-associated high-grade cervical intra-epithelial neoplasia (CIN-3). Controls for invasive cases and CIN-3 cases were women who had no cytologic abnormalities and who were matched for age and country of residence. Serum antibodies to HPV-16 E6 and E7 proteins were detected by radio-immunoprecipitation of in vitro translated proteins. Antibodies to the E6 and E7 protein were observed among 56% and 43%, respectively, of invasive cases and 1.7% and 4.1%, respectively, of controls. Antibodies to either protein were detected in 72% of sera from invasive cases and 5.8% of sera from controls. High antibody reactivity and antibodies to both proteins were found almost exclusively in invasive cases. The frequency of antibodies to the E6 protein and the E7 protein among CIN-3 cases did not differ significantly from the CIN-3 controls. Five women with HPV-18-associated invasive cervical cancer were negative for serum antibody to HPV-16 E6 and E7 proteins. Antibodies to HPV-16 E6 and E7 proteins appear to be partially virus-specific and disease state-specific markers of HPV-associated cervical cancer.

Antibodies, Viral↗
PubMed1998

Time since last use of oral contraceptives and risk of invasive cervical cancer.

The time-risk relationship for the association between cervical cancer and oral contraceptives (OC) was examined using data on 592 cases of invasive cervical cancer aged 60 years or less and 616 controls with acute, non-gynaecological, non-hormone-related, non-neoplastic diseases. A total of 125 cases and 114 controls reported ever using OC and the multivariate odds ratio (OR) for ever versus never users was 1.21 (95% confidence interval (CI) 0.82-1.74). The risk of invasive cervical cancer was above unity in current users (OR 1.23) and in women who had stopped OC use less than 10 years before diagnosis, but not in those who had stopped their OC use > or = 10 years before (OR 0.85). Similarly, the OR was less for women who had started OC use 15 years or more previously than for more recent users. These data suggest that OCs may have a late stage (promoter) effect on cervical carcinogenesis and thus have public health implications, since the incidence of invasive cervical cancers is low at young ages, when OC use is more common and increases during middle age. The absence of a persisting risk is therefore of interest both for assessing individual risk and for its public health implications.

Adolescent↗
PubMed2005

Increased expression of ICAM-3 is associated with radiation resistance in cervical cancer.

To search for a marker that predicts the efficacy of radiation therapy in human cervical cancer, gene expression profiles between parental SiHa cervical cancer cells and radiation-resistant SiHa/R cells have been compared by the microarray technique. Microarray and Northern blot analyses demonstrated that the ICAM-3 expression was upregulated in SiHa/R cells. This increased expression of ICAM-3 in SiHa cells enhanced cell survival by about 34.3% after a 2 Gy dosage of radiation. In addition, SiHa/ICAM-3 cells showed a 2.45-fold higher level of FAK phosphorylation than that of the control cells. In tumor specimens, ICAM-3 staining was restricted to tumor stromal endothelial cells and lymphocytes. The overexpression of ICAM-3 was significantly more frequent in radiation-resistant cervical cancer specimens when compared with radiation-sensitive specimens (83.3% vs. 35.3%; p = 0.015). With these observations, we can suggest that an increased expression of ICAM-3 is associated with radiation resistance in cervical cancer cells and the expression of ICAM-3 can be used as a valuable biomarker to predict the radiation resistance in cervical cancer that occurs during radiotherapy.

Antigens, CD↗
PubMed2000

Human papillomavirus (HPV) and cervical cancer.

Epidemiologic studies have consistently shown that the most important risk factor for cervical cancer relates to sexual activity and a sexually transmitted agent, probably a virus, is the principal causative agent. In recent years, much attention has been focused on the human papillomavirus (HPV) as the causative agent. The compelling epidemiologic evidence of the role of HPV in cervical cancer is complemented by equally strong data on the role of oncoproteins E6 and E7 of high-risk HPV strains in the molecular pathogenesis of cervical cancer. Incidence and mortality from cervical cancer have been decreasing steadily in most developed countries, but is the leading female cancer in developing countries. This variation in incidence is explicable in terms of differing levels of risk behaviour and population screening facilities and uptake. With better understanding of the aetiopathogenesis, vaccination against HPV is becoming a reality. This may be particularly useful in developing countries, where it is proving difficult to implement effective screening programmes.

Cause of Death↗
PubMed2000

Phase II study of irinotecan and cisplatin as first-line chemotherapy in advanced or recurrent cervical cancer.

Irinotecan (CPT-11) and cisplatin are singly active against cervical cancer. We evaluated the efficacy and toxicity of CPT-11 plus cisplatin as first-line chemotherapy in patients with advanced or recurrent cervical cancer. Twenty-nine chemotherapy-naive patients with advanced or recurrent cervical cancer were treated with CPT-11 (60 mg/m(2)) on days 1, 8, and 15 by intravenous infusion over 90 min, followed by cisplatin (60 mg/m(2) i.v.) on day 1 over 90 min. The patients' median age was 57 years (range 35-75). Nineteen patients (66%) had advanced primary disease. Six patients with recurrent disease (21%) had been treated with prior radiotherapy. The remaining 4 patients (14%) had residual or recurrent disease after radical surgery. The histologic diagnoses were squamous cell carcinoma in 25 patients (87%), adenocarcinoma in 3, and adenosquamous cell carcinoma in 1. All eligible patients were included in the toxicity and response analysis based on the intent to treat. Two patients (7%) achieved a complete response and 15 (52%) a partial response (overall response rate: 59%, 95% confidence interval; 41-74%). Stable disease was recorded in 6 patients (21%) and progressive disease in 3 patients (10%). In 3 patients, image-guided evaluation of response was judged to be unfeasible at the time of independent extramural review (10%). The median time to response was 32 days (range 16-62 days). The median survival was 27. 7+ months (range, 6.4-52.8+ months). Two dose-limiting side effects were observed: grade 3 (28%) or 4 (45%) neutropenia and grade 3 (7%) or 4 (7%) diarrhea. Other severe toxicities included anemia (45%), thrombocytopenia (3%), nausea/vomiting (31%), and alopecia (7%). The combination of CPT-11 with cisplatin is an active regimen for treatment of advanced or recurrent cervical cancer albeit with a significant degree of myelosuppression.

Adult↗
PubMed1996

Cervical intraepithelial neoplasia, cervical cancer, and HPV.

Major progress has been made to control cervical cancer in the United States and Europe using screening programs, although it remains a major cause of morbidity and mortality in the developing world. The association between cervical cancer and a sexually transmissible etiologic agent was hypothesized long before identification of human papillomaviruses (HPV) as agents that infected the genital tract. HPVs are among the most common sexually transmitted agents and have been shown to induce several squamous anogenital cancers, including squamous cell cancer of the cervix. After an etiologic role for HPV was identified in cervical cancer and CIN, efforts to understand the molecular biology of HPV were greatly expanded, enhanced by the advent of deoxyribonucleic acid (DNA) probes to identify HPV infection. Recent research has focused on specific types of HPV in relation to other recognized risk factors in the pathogenesis of CIN and invasive cervical cancer.

DNA Probes↗
PubMed2005

Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study.

BACKGROUND: Infection with human papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesion, cervical intraepithelial neoplasia (CIN). Variability in host immunogenetic background is important in determining the overall cellular immune response to HPV infections. OBJECTIVE: To determine whether the HLA-DQ or HLA-DR genes, or others in their vicinity, are associated with cervical cancer. METHODS: Markers covering the entire HLA region were genotyped in a large sample of CIN and cervical cancer patients and in controls (311 CIN, 695 cervical cancer, 115 family controls, and 586 unrelated controls). RESULTS: Two markers were associated with susceptibility to cervical neoplasia, G511525 and MICA. G511525, close to the region containing the HLA-DQ and HLA-DR genes, was most strongly associated, showing a decrease in frequency of allele 221 from 6.7% to 3.3% in patients with squamous cell cancer (SCC). An association was found for MICA (allele 184) with SCC (odds ratio (OR) = 1.31 (95% confidence interval, 1.13 to 1.53); homozygotes, OR = 1.48 (1.06 to 2.06)). No associations were observed with adenocarcinoma or CIN. CONCLUSIONS: There is an association of the region containing the HLA-DQ and HLA-DR genes with the risk of developing squamous cell carcinoma. An increased risk was observed for carriers of allele 184 at the MICA locus, in particular for homozygotes, suggesting a recessive effect.

Adenocarcinoma↗
PubMed2000

[Prognostic value of cell heterogeneity in cervical cancer determined by digital image analyzer of DNA content].

Frequency and prognostic value of cell heterogeneity in FIGO 1a-2a cervical cancer was examined, in 66 of patients underwent Wertheim type hysterectomy between 1989 and 1995 in National Institute of Cancer, Budapest, Hungary. A newly developed DNA image analyses (DNACE) was used in paraffin embedded tissues after enzymatic hydrolyses for evaluation of the DNA content in cervical cancer. In 30.3% of examined tissues (20/66) two subgroups was found. There was significant differences in the DNA indexes (DI) between the subgroups (p = 0.0001). In the remaining 69.7% of the cases only one subgroup was present. The frequency of two subgroups was higher between aneuploid (78.4%), or hyperploid (81.5%) type cervical cancer, however there was no significant difference between the two groups. On the other hand there was significant difference in the presence of two subgroups between the well and less differentiated cervical cancer. The frequency was higher between the less differentiated groups (p = 0.02). Looking at the prognostic value of subgroups, there was no significant correlation between the heterogeneity of cervical cancer and FIGO stage, or lymph node metastasis (p = 0.6855), or vascular/lymphatic space infiltration (p = 0.2558), or invasiveness of cancer (0.0823). There was neither significant value found between the outcome of disease and the number of subgroups present (p = 0.8738). It is though that the present of cellular heterogeneity in cervical cancer is connected with the differentiation of the cancer cells, and can be a good prognostic value in the anticipation of the aggressiveness of cervical cancer. Looking at the present result, there was no significant connection between the heterogeneity of cervical cancer and the outcome of the disease, so further examination should be done.

DNA, Neoplasm↗
PubMed2025

Genome-Wide Association Analyses of HPV16 and HPV18 Seropositivity Identify Susceptibility Loci for Cervical Cancer.

Infection by high-risk human papillomavirus is known to exacerbate cervical cancer development. The host immune response is crucial in disease regression. Large-scale genetic association studies for cervical cancer have identified few susceptibility variants, mainly at the human leukocyte antigen locus on chromosome 6. We hypothesized that the host immune response modifies cervical cancer risk and performed three genome-wide association analyses for HPV16, HPV18 and HPV16/18 seropositivity in 7814, 7924, and 7924 samples from the UK Biobank, followed by validation genotyping in the German Cervigen case-control series of cervical cancer and dysplasia. In GWAS analyses, we identified two loci associated with HPV16 seropositivity (6p21.32 and 15q26.2), two loci associated with HPV18 seropositivity (5q31.2 and 14q24.3), and one locus for HPV16 and/or HPV18 seropositivity (at 6p21.32). MAGMA gene-based analysis identified HLA-DQA1 and HLA-DQB1 as genome-wide significant (GWS) genes. In validation genotyping, the genome-wide significant lead variant at 6p21.32, rs9272293 associated with overall cervical disease (OR = 0.86, p = 0.004, 95% CI = 0.78-0.95, n = 3710) and HPV16 positive invasive cancer (OR = 0.73, p = 0.005, 95% CI = 0.59-0.91, n = 1431). This variant was found to be a robust eQTL for HLA-DRB1, HLA-DQB1-AS1, C4B, HLA-DRB5, HLA-DRB6, HLA-DQB1, and HLA-DPB1 in a series of cervical epithelial tissue samples. We additionally genotyped twenty-four HPV seropositivity variants below the GWS threshold out of which eleven variants were found to be associated with cervical disease in our cohort, suggesting that further seropositivity variants may determine cervical disease outcome. Our study identifies novel genomic risk loci that associate with HPV type-specific cervical cancer and dysplasia risk and provides evidence for candidate genes at one of the risk loci.

Humans↗
PubMed1999

The antibody response to HPV proteins and the genomic state of HPVs in patients with cervical cancer.

Human papillomavirus (HPV) DNAs are often found to be integrated into the human genome in high-grade cervical intraepithelial neoplasia (CIN) as well as in invasive cervical cancers. Investigation of the relationship between the genomic status of specific HPV genes and their antibody responses to the virus-like particles (VLPs) of HPV-16 L1/L2 proteins and the in vitro translated HPV-16 E6 and E7 proteins may help to illustrate the mechanism of HPV-related cervical carcinogenesis and host immune response. Cervical cancer tissues obtained from 39 patients were studied to evaluate the physical status of HPV genes by Southern blotting, DNA-PCR, and RT-PCR of E2. The antibody response against the HPV-16 L1/L2 VLPs of serum specimens were tested by ELISA and the antibody response against the HPV-16 E6 and E7 proteins were tested by radioimmunoprecipitation assay (RIPA), respectively. Integrated forms of HPV-16 DNA were found in 23 of the 38 patients (60.5%). The HPV-16 positive cervical cancer patients showed a significantly higher prevalence rate (39.5%; 15/38) of antibodies to HPV-16 L1/L2 VLPs than that of the control group (8.7%; 2/28) (P < 0.05). Antibodies to HPV-16 L1/L2 VLPs were more commonly detectable in cervical cancer patients having the episomal form of HPV-16 DNA (pure episomal and mixed forms) (60%; 9/15) than in those who had only the integrated forms of HPV-16 DNA (26.1%; 6/23) (P < 0.05). Antibodies to E6 and E7 proteins were positive in 36.8% (14/38) and 50% (19/38) of the patients with HPV-16 positive cervical cancer, respectively. These were significantly higher than the positive rates for the control group (8.3% and 2.8%) (P < 0.05). The differences between sero-reactivities to E6 and E7 proteins in the patients with episomal forms of HPV-16 DNA and those with integrated forms of HPV-16 DNA were not statistically significant (P > 0.05). Integrated forms of HPV-16 DNA were prevalent in most patients with cervical cancer in Korea. Antibodies to HPV-16 L1/L2 VLPs, in vitro translated HPV-16 E6 and E7 proteins, appeared in a significantly larger proportion of the HPV-associated cervical cancer patients than in the controls. Antibodies to HPV-16 L1/L2 VLPs were more often detected in cervical cancer patients having the episomal form of HPV-16 DNA than in those having only integrated forms of HPV-16 DNA. Antibody responses to HPV-16 E6 and E7 proteins were not influenced by the different viral states.

Journal Article↗
PubMed2002

Expression and accumulation of lumican protein in uterine cervical cancer cells at the periphery of cancer nests.

Lumican is a member of a small leucine-rich proteoglycan (SLRP) family and is reported to be overexpressed during the wound healing process of the cornea, and ischemic and reperfused heart. In the carcinomatous tissues, lumican is overexpressed in human breast and pancreatic cancer tissues. In the present study, we aimed to clarify the expression of lumican mRNA and its protein in human cervical cancer cell lines (CaSki, ME-180 and HeLa cells) and their localization in normal and cancerous human cervical tissues. Reverse transcription-polymerase chain reaction and Western blot analysis revealed the expression of lumican mRNA and its protein in CaSki, ME-180 and HeLa cells. No or weak immunoreactivity of the lumican protein was observed in stroma but not in squamous and ductal cells of non-cancerous uterine cervical tissues. In 21 of 28 (75%) cervical cancer cases, the lumican protein was strongly expressed in cancer cells, and accumulated particularly in cancer cells at the periphery of the cancer nests. It was also expressed in the fibroblasts adjacent to the cancer cells. In situ hybridization analysis revealed that lumican mRNA was not expressed in squamous or ductal epithelial cells in non-cancerous tissues, but was expressed in most cancer cells and stromal fibroblasts in uterine cervical cancer tissues. The lumican protein was not localized in normal squamous or ductal cells close to cancer cells, but its mRNA was strongly expressed in the same cells. To our knowledge, this is the first report on lumican synthesized by squamous cell carcinomas. These findings may indicate that the accumulated lumican protein in cancer cells at the periphery of cancer nests may play roles in the growth or invasion of human cervical cancer cells.

Blotting, Western↗
PubMed1997

Prospective seroepidemiologic study of human papillomavirus infection as a risk factor for invasive cervical cancer.

BACKGROUND: Major risk factors for invasive cervical cancer include infection with human papillomavirus (HPV), infection with other sexually transmitted pathogens (e.g., Chlamydia trachomatis), and smoking. Since exposures to these risk factors can be related, the contribution of any single factor to cervical carcinogenesis has been difficult to assess. We conducted a prospective study to define the role of HPV infection in cervical carcinogenesis, with invasive cancer as an end point. METHODS: A nested case-control study within a joint cohort of 700,000 Nordic subjects was performed. The 182 women who developed invasive cervical cancer during a mean follow-up of 5 years were matched with 538 control women on the basis of age and time of enrollment. Serum samples taken at enrollment were analyzed for evidence of tobacco use (i.e., cotinine levels); for antibodies against HPV types 16, 18, and 33; and for antibodies against C. trachomatis. Relative risks (RRs) were estimated by use of conditional logistic regression. RESULTS: Presence of antibodies against HPV in serum (seropositivity) was associated with an increased risk of cervical cancer, and adjustment for smoking and for C. trachomatis seropositivity did not affect this finding (RR = 2.4; 95% confidence interval [CI] = 1.6-3.7). HPV16 seropositivity was associated primarily with an increased risk of squamous cell carcinoma (RR = 3.2; 95% CI = 1.7-6.2). In contrast, risk associated with HPV18 seropositivity tended to be higher for cervical adenocarcinoma (RR = 3.4; 95% CI = 0.8-14.9). In populations with a low prevalence of antibodies against C. trachomatis, the HPV16-associated risk of cervical cancer was very high (RR = 11.8; 95% CI = 3.7-37.0); in contrast, in populations with a high prevalence of antibodies against C. trachomatis, no excess risk was found. CONCLUSION: Past infection with HPV16 increases the risk of invasive cervical squamous cell carcinoma, most clearly seen in populations with a low prevalence of sexually transmitted diseases.

Adenocarcinoma↗
PubMed2003

Detection of epidermal growth factor receptor mRNA in peripheral blood of cervical cancer patients.

OBJECTIVE: Epidermal growth factor receptor (EGFR) has been reported to be expressed by immunohistochemistry in invasive cervical cancers. We evaluated the feasibility of detecting EGFR mRNA by EGFR-based reverse transcription polymerase chain reaction (RT-PCR) in peripheral blood of patients with cervical cancer. METHODS: Expression of EGFR mRNA, cytokeratin (CK)-19 mRNA, and CK-20 mRNA was examined by RT-PCR in 12 human cervical cancer cell lines. All 12 cell lines expressed both EGFR mRNA and CK-19 mRNA, but only 4 of 12 (33.3%) cell lines expressed CK-20 mRNA. Peripheral blood samples from 20 healthy donors and 45 cervical cancer patients were also examined. RESULTS: In peripheral blood from 20 healthy donors, neither EGFR mRNA nor CK-20 mRNA was expressed, but CK-19 mRNA was expressed in 13 of 20 (65%). In contrast, EGFR mRNA was expressed in 12 of 45 (26.7%) patients with cervical cancer (P = 0.0071, 2 test, patient vs control). On the other hand, expression of EGFR was observed in 98% of tumor tissues by immunohistochemistry. CK-19 mRNA and CK-20 mRNA were found in 35 of 45 (77.8%) and 0 of 45 (0%) patients, respectively (NS, chi(2) test, patient vs control). The rate of detection of EGFR mRNA in peripheral blood correlated with FIGO stage (P = 0.049). CONCLUSION: Both CK-19 mRNA and CK-20 mRNA showed no diagnostic value as markers of circulating tumor cells in cervical cancers. However, EGFR mRNA in blood might be a useful marker of circulating tumor cells in cervical cancers.

Carcinoma, Squamous Cell↗
PubMed2005

[Diagnosis of papilloma viruses in cervical cancer in 414 women from Wielkopolska region by the immunohistochemical assessment].

OBJECTIVES: Cervical cancer in Poland is second most common type of cancer, after breast cancer. There are known risk factors of cervical cancer development and the most serious one is human papilloma virus infection (HPV). DESIGN: The aim of our paper is present the result study 414 cervical cancer of women from Wielkopolska region treated at the Department of Gynecology and Obstetrics, Karol Marcinkowski University of Medical Sciences in Poznań. MATERIALS AND METHODS: In morphological study grading, staging and vascular invasion were estimated. In cervical cancer tissue papillomaviruses PCR method were used. In immunohistochemical study, expression of proteins checking the cell cycle, share in signal transduction to nucleus, cell receptors for steroid hormones and viruses oncogenic proteins were investigated. In the part of cancer gene mutation of p53 (60 cancers) i k-RAS (40 cancers) were searched. RESULTS: In cancers HPV 16/18 infected vascular invasion were more frequently (p < 0.013). No statistically significant difference in cellular proteins expression in the HPV16/18 positive cancers, HPV16/18 negative and cancers without HPV was observed. However significant difference were demonstrated in proteins expression depending from degree of cancer stage. CONCLUSIONS: The result of these studies suggest that super expression for EGFr is poor prognostic factor in the early stage of cancers (I-II0).

Adult↗
PubMed1999

Increase in cervical cancer mortality in Spain, 1951-1991.

BACKGROUND: The trend in cervical cancer mortality in Spain from 1951 to 1991 is examined. METHODS: Analysis of national mortality statistics calculating age standardised mortality rates and an age-period cohort analysis. A fit to the Gompertz function was made to estimate the influence of the environmental factors on the mortality rates evolution. MAIN RESULTS: The age standardised mortality rate in Spain is lower than in other developed countries (USA or Estonia) and equal to Norwegian and Finland rates; but whereas in these countries the trend is to decrease, the Spanish rate has increased during this period, because of a cohort effect. A misclassification bias could be responsible for the trend in women aged 40 and older but the increasing trend in younger women could not be interpreted as espurious. The Gompertzian analysis suggests an increase in environmental factors causing cervical cancer. CONCLUSIONS: Cervical cancer mortality rates are increasing in Spain because of environmental factors.

Adult↗