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Knowledge of cervical cancer screening and use of cervical screening facilities among women from various socioeconomic backgrounds in Durban, Kwazulu Natal, South Africa.

The value of screening for cervical cancer has been proven. Such screening in developed countries has achieved a decrease in incidence and mortality by about 80%. Although screening facilities are available in certain parts of developing countries, the incidence of cervical cancer remains very high and many patients present with late stage disease. The study was performed among women from different socioeconomic circumstances (low, middle, and upper social/financial backgrounds). The assessment was performed by means of a questionnaire. The majority of patients from lower socio-economic circumstances with multiple risk factors were not aware of cervical screening or facilities available for this purpose. However, in spite of knowledge of cervical screening and the availability of such services, the majority of women (87%) from higher social and educational backgrounds did not undergo cervical screening. Most patients resided within a 12-kilometer radius of a facility that either provided or could potentially provide screening. Although some patients (36.7%) had had a screening test performed at some time in the past, only 27.3% of patients reported having had a Pap test. This was due to failure on the part of the healthcare giver to disseminate information to the patient regarding the reason and value of cervical screening. Among women from higher socioeconomic groups, the level of education was better and knowledge of the Pap test was not age-dependent. We conclude that the mere provision of a cervical cancer screening service is not sufficient to ensure successful uptake since screening is a multifaceted entity. Improvement of socioeconomic and educational circumstances should improve the uptake of a screening program only if the healthcare giver provides appropriate information to the patient and the patient takes the initiative to avail themselves of such screening.

Adolescent↗

Circulating serum levels of cytokines and angiogenic factors in patients with cervical cancer.

Progression of cervical cancer is associated with excessive circulating levels of cytokines, which are known to be modulators of tumor angiogenesis. The concentrations of cytokines and growth factors were assayed using enzyme-linked immunosorbant assays in the serum of 61 women in various stages of cancer [stage 0 (n = 6), stage I (n = 15), stage II (n = 15), stage III (n = 15), and stage IV (n = 10)] and of 20 healthy control subjects. Our results indicated that b-FGF and TNF-beta levels were significantly elevated in stage I, and serum levels of TGF-beta and IL-7 were elevated in stages II-IV of invasive carcinoma. Our experimental subjects had significantly increased serum levels of IL-6, GM-CSF, and angiogenin in stages I-IV of cervical cancer, and TNF-alpha serum levels were elevated in all stages of invasive carcinoma. The serum levels of IL-8 and IL-10 were elevated only in stages II-III, and the levels of IL-2 were elevated in stages III-IV. The serum levels of IL-1 alpha and IL-1 beta remained unaltered in all stages of cancer progression. Progression of cervical cancer is associated with increased serum levels of angiogenin, IL-2, IL-6, IL-7, IL-8, IL-10, b-FGF TNF-alpha, TGF-beta, TNF-beta, and GM-CSF during different stages, all of which have the potential to be angiogenic amplifiers.

Adult↗

[Radical vaginal trachelectomy for invasive cervical cancer].

The use of operative laparoscopy in gynecologic oncology has paved the way to a more conservative approach in radical treatments of some cancers, particularly cervical cancer. After the vaginal approach which shortens the hospital stay and the morbidity of a radical hysterectomy, a new fertility-preserving radical treatment has been proposed : the Radical Vaginal Trachelectomy (RVT). This technique has been used since 1991 in our institution. Until July 1999, 37 patients with early-stage cervical cancer desiring to retain their fertility were treated by a laparoscopic pelvic lymphadenectomy (LPL) and RVT. The median age was 32 (22-42), and 25 were nulliparous. Twelve were FIGO stage Ia2, 22 Ib1, 2 IIa and one Ia1 (VSI+). Most of the tumors were squamous (23), grade I (21), and the lesion was 2cms or less in 35 patients. Median operating time was 275 minutes ( 200 for the last 10 cases), and blood loss 200cc. Complications were mainly due to the LPL (3 arterial injuries) rather than the RVT (one iatrogenic cystotomy and one parametrial bleeding). The mean follow-up is 42 months. Two patients recurred including one who had a small-cell neuroendocrine tumor. Ten patients had a total of 13 pregnancies with 7 live births. One newborn died of E.coli-septicemia. Two patients had early miscarriages and 2 second trimester abortions (17 and 20 weeks). Two patients are still pregnant. LPL-RVT seems to be a good treatment modality for early-stage cervical cancer. It preserves fertility without lowering the chances of survival.

Adult↗

Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in human cervical cancers.

OBJECTIVE: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a classical glycolytic protein. A higher level of GAPDH mRNA was found in lung, pancreas, and prostate cancers, but in cervical carcinoma there have not been any reports about the level of GAPDH gene expression. So, we tried to investigate the GAPDH gene expression patterns in cervical carcinomas compared to normal cervical tissues, and the relationships between the expression levels of this gene and conventional clinicopathological parameters were evaluated. MATERIALS AND METHODS: In this study, 25 normal exocervical tissues, 35 primary untreated cervical cancer tissues, 2 cervical cancer cell lines, and 2 post-nude-mouse-derived cervical cancer cell lines were subjected to Northern blot analyses for GAPDH gene expression. RESULTS: Northern blot analyses revealed that the levels of GAPDH gene expression were elevated in 34 of 35 (97%) cervical carcinoma tissues and all of the 4 cervical cancer cell lines compared to normal cervical tissues. The levels of GAPDH gene expression were more prominent in rapidly proliferating cervical carcinoma cells. The levels of the GAPDH gene expressions in cervical cancer tissues were not associated with conventional clinicopathological parameters including clinical stage, histological type, and degree of differentiation. CONCLUSION: These results suggest that increased GAPDH gene expression is characteristic of human cervical carcinomas and that rapidly proliferating carcinoma cells express more enhanced GAPDH gene. Future gene therapy using antisense oligodeoxynucleotide directed against GAPDH mRNA might be another therapeutic tool for human uterine cervical carcinoma.

Female↗

[Evaluation of a new anti-cancer drug regimen against uterine cervical cancer in nude mice].

The purpose of this study was to describe a new anti-cancer drug regimen for uterine cervical cancer. The cytotoxicities of some anti-cancer drugs regimens against the human uterine cervical cancer xenografted into nude mice have been studied. The activities of CDDP, CPT-11, TXL, CDDP + BLM, CDDP + MMC, CPT-11 + BLM, CPT-11 + CDDP, CDDP + 5-FU, CPT-11 + MMC, CPT-11 + TXL and CDDP + TXL for squamous cell carcinoma (TCR, TCK, TCG), and CDDP, MMC, TXL, CDDP + TXL, CDDP + MMC and MMC + TXL for adenocarcinoma (TCO, TCM, TCY), were evaluated comparing with a control group using saline. Five mice were used for each groups. When the xenografted tumor reached 6 mm in diameter, 1/5 LD50 of these drugs were administered into the peritoneal cavity of the mice once a week for three weeks. The effective regimens were CDDP + MMC, CDDP + BLM, CDDP + CPT-11 and CPT-11 + MMC for squamous cell carcinoma of the uterine cervix. CDDP + MMC, CDDP + TXL, MMC + TXL and CDDP were effective for endocervical adenocarcinoma. It was suggested that these new drug regimens should be used in clinical studies.

Adenocarcinoma↗

[A study on the relationship between human papilloma virus (HPV) and cervical cancer].

Samples of cervical tissues of patients from Shandong province were detected by using Southern blot hybridization technique of nucleic acid with the probe of (alpha-32P)-dCTP HPV16 DNA fragment cleaving with BamHI. The total positive rate of HPV16 DNA related sequences in 116 cases with cervical cancer was 50.9%, and much higher than that in 36 cases with non-cervical disease (5.6%). There is a strong correlation between the HPV and cervical cancer (OR = 17.60, P less than 0.001). It was showed that there was no association between the positive rate of HPV 16 DNA related sequences and age, clinical period and local appearance in cases with cervical cancer. This was the first paper described that HPV 33 DNA sequences were found in four cervical carcinoma samples, and HPV 31 DNA sequence in one cervical carcinoma sample under low stringent conditions of hybridization in Shandong province.

Adult↗

Polymorphic amino acids at codons 9 and 37 of HLA-DQB1 alleles may confer susceptibility to cervical cancer among Chinese women.

Cervical cancer is strongly associated with the infection by oncogenic forms of human papillomavirus (HPV). Although most women are able to clear HPV infection, some develop persistent infections that may lead to cancer, implying genetic susceptibility factors for malignant progression. To verify whether HLA class II DQB1 polymorphism is related to cervical cancer in Chinese population, HLA-DQB typing was carried out by PCR-SBT for 258 patients with cervical cancer and 284 healthy controls, and the allele frequencies were calculated. In this study, HLA-DQB1*060101 and DQB1*0602 alleles were significantly higher in the HPV16 infected patients with cervical cancer compared with healthy controls (chi(2) = 31.7452, p < 0.0001; chi(2) = 12.7838, p(c) = 0.0066), but DQB1*050201 allele was significantly lower (chi(2) = 26.2187, p < 0.0001). This result indicates that HLA-DQB1*060101 and DQB1*0602 may confer susceptibility to cervical cancer, and DQB1*050201 may contribute to the resistance to the development of cervical cancer among Chinese women. Sequence analysis reveals that DQB1*060101 allele encodes Leu at position 9 and Asp at position 37, unique to the susceptibility to cervical cancer, whereas the other DQB1 alleles encode Phe or Tyr and Ile or Tyr at the same two positions, respectively. This finding implies that polymorphic amino acids at the putative antigen binding residues 9 and 37 of HLA-DQB1 alleles may play an important role in the development of cervical cancer.

Amino Acid Sequence↗

[Cervical cancer despite prevention. Clinical and histomorphologic study of 255 cervical cancers from 1974 to 1980 with regard to a 2d aggressively growing cancer type].

Historical data, histological parameters and follow-up findings were reviewed both in 75 "prophylaxis failures" and in 255 cases of clinical cervical carcinoma treated surgically (Wertheim's procedure); all of these cases were diagnosed between 1974 and 1980. In 29.5% of the patients preventive care or respectively gynaecological examination failed. The many and varied causes of errors are discussed. Neither the histological tumour type, nor the lymph-node metastasis rate, nor the frequency of recurrence, nor the mortality figures are indicative of a more aggressive type of tumour in the "prophylaxis failures". Mortality among the latter is 13.3%, as opposed to 15.3% in the entire patient collective, the lymph-node metastasis rate 25.3% as compared to 31.8% overall, and the recurrence rate 18.1% as compared to 18.8% overall. As expected, cases with obviously delayed diagnosis have the highest mortality rate, i.e., 25% as against 15.3% overall. There is not a single case in which cancer can be shown to have developed without a preceding precancerous stage. It is suspected that mistakes made while obtaining smears are the principal cause of failure of prophylaxis, followed by errors of evaluation, in histology, and in therapeutic measures taken after histological confirmation of cervical neoplasm. These results do not in any way exclude an aggressive type of tumour in rare individual cases; however, the occurrence of such a tumour would be an exception.

Adenocarcinoma↗

The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life questionnaire cervical cancer module: EORTC QLQ-CX24.

BACKGROUND: The authors report on the development and validation of a cervical cancer module for the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life (QoL) questionnaire (QLQ), which was designed to assess disease-specific and treatment-specific aspects of QoL in patients with cervical cancer. METHODS: The cervical cancer module (EORTC QLQ-CX24) was developed in a multicultural, multidisciplinary setting to supplement the EORTC QLQ-C30 core questionnaire. The QLQ-C30 and the cervical cancer module were administered to 346 patients with cervical cancer who underwent radical hysterectomy and received radiotherapy and chemotherapy. Psychometric analyses were performed by using data from 2 independent samples. RESULTS: The QLQ-CX24 consists of 3 multiitem scales and 5 single-item scales. Multitrait scaling analyses revealed high internal consistencies for the subscales with Cronbach alpha coefficients ranging from .72 to .87 (Symptom Experience, .72; Body Image, .86; Sexual/Vaginal Functioning, .87). Convergent and discriminant validity were fulfilled with scaling errors below 3%. The QLQ-CX24 was capable of discriminating between clinical subgroups. All items exhibited good compliance with <3% missing values. Most patients completed the EORTC QLQ-C30 and the QLQ-CX24 in <15 minutes (86%), and many did not require any assistance to complete the questionnaires (65%). CONCLUSIONS: The current psychometric analyses supported the content and construct validity and the reliability of the EORTC QLQ-CX24 module. This newly developed module is a useful instrument for assessing the QoL of patients who are treated for cervical cancer both in clinical trials and in clinical practice.

Adult↗

Surface protein expression and messenger RNA-splicing analysis of CD44 in uterine cervical cancer and normal cervical epithelium.

Variant CD44 has recently been shown to serve as a metastasis marker in human breast cancer. Certain variant epitopes on primary tumors predict poor survival probabilities for the patients. In this study, immunohistochemical analysis of 16 uterine cervical carcinomas showed strong expression of several CD44 variant epitopes in all samples. In normal cervical epithelia from 5 patients, expression of these epitopes was restricted to particular cell layers, with expression being strong in basal and spinal cells but absent in superficial cells. Fifteen of 16 cancer samples were stained strongly with an antibody which recognizes one particular CD44 epitope that is encoded by both variant exons v7 and v8. This epitope was not detectable in normal cervical epithelium. CD44-mRNA splicing analysis showed qualitative and quantitative differences between malignant and normal tissues with a much more complex splice pattern and high expression of a large CD44 isoform containing variant exons v3 to v10 (including the v7/v8 transition epitope) in about one-half of the cancer samples. Interestingly, patients with lymph node metastases were in this group only. These differences in CD44 epitope expression and mRNA splicing in cervical carcinoma reveal dynamic changes in CD44 expression during carcinogenesis. Such changes could provide metastatic cells with a selective advantage during the carcinogenic process. Furthermore, the v7/v8 epitope may be suitable for screening early stages of cervical cancer.

Adenocarcinoma↗

Human papillomavirus typing and the reduction of cervical cancer risk.

Minor cervical cytologic abnormalities are common, but knowing which low-grade lesions will progress to cervical cancer--and therefore deserve biopsy and excision--is difficult. Since some human papillomavirus (HPV) types are strongly associated with cervical cancer, HPV typing may be a means of determining which patients with minor abnormalities require biopsy and treatment and which need only follow-up smears. This paper reviews the association between cervical cancer and HPV infection, the pathogenesis of HPV infection, the utility of HPV typing in training patients with a diagnosis of atypical squamous cells of undetermined significance, and the prospects for the development of an HPV vaccine.

Female↗

Cervical epidermal growth factor-receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer.

PROBLEM: To ascertain if cervical epithelial epidermal growth factor receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer. METHOD OF STUDY: We tested cervical biopsies obtained from 18 controls, 3 women with cervical intraepithelial neoplasia (CIN) I, 17 women with CIN II and III, and 12 women with cervical cancer for EGF-R using a quantitative immunofluorescent antibody assay. We measured serum IGF-II levels using an enzyme-linked immunosorbent assay in 20 controls, 26 CIN patients, 12 with cervical cancer before therapy, 5 with cervical cancer for < 1 year, and 9 others > 1 year after therapy. RESULTS: The levels of cervical EGF-R in women with CIN and cervical cancer were significantly higher (P<0.05 for CIN I; P<0.001 for patients with CIN II and III or cervical cancer) than in controls. Women with cervical cancer (P<0.001 vs. controls) or advanced CIN (P = 0.03) had elevated levels of serum IGF-II, while the women with CIN I had levels similar to controls. Women with cervical cancer in the post-therapy period had significantly lower serum IGF-II levels than the women with cervical cancer before therapy (P<0.001). CONCLUSION: Cervical epithelial EGF-R and serum IGF-II levels may be used for the diagnosis and prognosis of cervical cancer.

Biomarkers, Tumor↗

Risk factors of invasive cervical cancer in Mali.

BACKGROUND: Cervical cancer is the most common cancer in women in Mali and the second commonest cause of cancer mortality. METHODS: As part of an international effort to evaluate the role of human papillomavirus (HPV) in the aetiology of cervical cancer, we conducted a hospital-based case-control study in three medical centres in Bamako during 1994-1995. A total of 82 cases (invasive cervical cancer patients) and 97 controls matched to the cases for age were included. Information on risk factors was collected through personal interview. Serum antibodies to HPV 16, 18 and 31 virus like particles (VLP) were detected using ELISA assays. Polymerase chain reaction was used to detect HPV DNA in frozen biopsies of cases. RESULTS: Human papillomavirus 6, 18, 31 VLP were detected in 60.4% of cases and 45.4% of controls (P = 0.03). Overall, HPV DNA was identified in 96.9% of the cervical cancer cases. Risk factors for cervical cancer were parity >10 versus <5 children ([odds ratio] OR = 4.8, 95% CI : 1.5-14.7), never having practised vaginal douching (OR = 17.6, 95% CI : 4.2-74.7), re-using home-made feminine napkins (OR = 45.9, 95% CI : 8.8-238.7) and having a husband with more than two wives (OR = 5.3, 95% CI : 1.3-21.3). CONCLUSIONS: These data provide further evidence on the role of HPV in cervical cancer and show that high parity and poor genital hygiene conditions were the main co-factors for cervical cancer in this population with prevalent HPV infection.

Adult↗

A population-based seroepidemiological study of cervical cancer.

The epidemiology of cervical cancer indicates the presence of a sexually transmitted risk factor, attributable at least in part to infection with human papillomavirus (HPV) type 16 or 18. We performed a seroepidemiological study of HPV and cervical cancer in the counties of Västerbotten and Norrbotten in Northern Sweden, a low-risk area for cervical cancer. Sera from 94 cases of incident cervical cancer were matched against 188 age- and sex-matched controls derived from a population-based blood bank. IgG and IgA antibodies were measured against a panel of 12 antigens derived from HPV types 6, 11, 16, or 18, as well as against Herpes simplex virus type 1 and 2, Chlamydia trachomatis, cytomegalovirus, Epstein-Barr virus, and bovine papillomavirus. Significantly increased relative risks (RRs) were found for IgG to HPV 16- or 18-derived antigens from the L1 (RR = 3.1), E2 (RRs = 2.8 and 9.2), and E7 (RRs = 3.8 and 2.7) open reading frames and for IgA to HPV 16-derived antigens from the E2 (RR = 3.3) and E6 (RR = 2.7) open reading frames. The highest RR (9.2, confidence intervals 4.4-19.4) was associated with IgG to an HPV 18 E2 antigen. Antibodies against cytomegalovirus, Herpes simplex virus type 2, Epstein-Barr virus, or bovine papillomavirus were, on their own, not significantly associated with cervical cancer, but seropositivity against multiple infections was associated with a successively increased relative risk. An increased risk was also found for IgG to Chlamydia trachomatis (RR = 1.7, confidence interval = 1.0-2.7). The results indicate that several HPV antibodies are strongly associated with cervical cancer, providing further seroepidemiological support for an etiological role of HPV in cervical cancer.

Adult↗

Telomerase in relation to clinicopathologic prognostic factors and survival in cervical cancer.

We investigated, in cervical cancer, the relation between telomerase activity, telomerase RNA (hTR) and mRNA of the catalytic subunit of telomerase, hTERT, with "classic" clinicopathological factors as well as survival. Frozen specimens were obtained from 107 consecutive patients with cervical cancer, treated with surgery or radiotherapy with or without chemotherapy. Telomerase activity was determined with fluorescence-based TRAP and hTR and hTERT with semi-quantitative RT-PCR. Eight normal cervical specimens served as controls. Analysis of prognostic factors and survival was limited to early-stage patients, treated primarily with radical hysterectomy. Telomerase activity was not detected in normal cervices and was present in 85 of 107 (79%) cervical cancers (p < 0.001). hTR was detected in all normal cervices and cervical cancers, while hTERT mRNA was detected in 1 of 8 (13%) normal cervices and in 83 of 104 (80%) cervical cancers (p < 0.001). In contrast to semi-quantitative hTR expression levels, semi-quantitative hTERT mRNA levels were related to telomerase activity levels (p < 0.01). In all patients, telomerase activity levels were related to differentiation grade (p < 0.05) but not to stage and histotype. In early-stage patients, telomerase activity, hTR and hTERT were not related to tumor volume, vascular invasion or presence of metastatic lymph nodes. Tumor volume, vascular invasion and presence of metastatic lymph nodes were related to (progression-free) survival, while telomerase activity and its subunits were not. Frequent up-regulation of telomerase activity and hTERT mRNA is especially observed in cervical cancers, while hTR is also detected in normal cervices. Telomerase is not applicable as a prognostic factor in early-stage cervical cancer patients.

Cervix Uteri↗