BACKGROUND: We wanted to review our 7-year experience using the loop electrical excision procedure (LEEP) for the treatment of cervical dysplasia in a family practice residency setting in the rural South. METHODS: We conducted a retrospective study with data gathered from chart review of a mostly Medicaid and uninsured patient population of rural Southern women referred from outlying health departments or private practices within an 80-mile radius. The women received follow-up Papanicolaou smears, and outcome measurements were either recurrence of dysplasia or at least 1 year with two negative Papanicolaou smears. Any surgical tissue obtained after LEEP was used to ascertain residual or recurrent dysplasia. RESULTS: Rates of disease recurrence and incomplete excision of cervical intraepithelial neoplasia grade 2/3 (CIN 2/3) compared favorably with results published by expert US gynecologists but were worse than those reported by European authors, who excise all CIN (CIN 1, CIN 2, and CIN 3). CONCLUSION: CIN 2 and CIN 3 can be diagnosed and treated appropriately with LEEP in the setting of a family practice residency. (+info)
Hypoxia-inducible erythropoietin signaling in squamous dysplasia and squamous cell carcinoma of the uterine cervix and its potential role in cervical carcinogenesis and tumor progression.
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Tissue hypoxia is a characteristic property of cervical cancers that makes tumors resistant to chemo- and radiation therapy. Erythropoietin (Epo) is a hypoxia-inducible stimulator of erythropoiesis. Acting via its receptor (EpoR), Epo up-regulates bcl-2 and inhibits apoptosis of erythroid cells and rescues neurons from hypoxic damage. In addition to human papillomavirus infection, increased bcl-2 expression and decreased apoptosis are thought to play a role in the progression of cervical neoplasia. Using reverse transcriptase-polymerase chain reaction and Western blotting we showed that HeLa and SiHa cervical carcinoma cells and human cervical carcinomas express EpoR, and that hypoxia enhances EpoR expression. Exogenous Epo stimulated tyrosine phosphorylation and inhibited the cytotoxic effect of cisplatin in HeLa cervical carcinoma cells. Using immunohistochemistry, we examined the expression of Epo, EpoR, p16, hypoxia-inducible factor (HIF)-1alpha, and bcl-2 in benign and dysplastic cervical squamous epithelia and invasive squamous cell carcinomas (ISCCs). EpoR expression in benign epithelia was confined to the basal cell layers, whereas in dysplasias it increasingly appeared in more superficial cell layers and showed a significant correlation with severity of dysplasia. Diffuse EpoR expression was found in all ISCCs. Expression of Epo and HIF-1alpha was increased in dysplasias compared to benign epithelia. Focal Epo and HIF-1alpha expression was seen near necrotic areas in ISCCs, and showed correlation in their spatial distribution. Significant correlation was found between expression of EpoR, and p16 and bcl-2 in benign and dysplastic squamous epithelia. Our results suggest that increased expression of Epo and EpoR may play a significant role in cervical carcinogenesis and tumor progression. Hypoxia-inducible Epo signaling may play a significant role in the aggressive behavior and treatment resistance of hypoxic cervical cancers. (+info)
Cervical dysplasia: early intervention.
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Cervical cancer is the second-most common cancer in young women and is one of the most common causes of cancer deaths among women, particularly in minorities and in impoverished countries. Cervical dysplasia, a premalignant lesion that can progress to cervical cancer, is caused primarily by a sexually transmitted infection with an oncogenic strain of the human papillomavirus (HPV). Not all women with the virus develop cervical dysplasia or cervical cancer. It has been postulated there are multiple host factors that contribute to progression of disease. Many of these factors, such as nutrient deficiencies, can be reversed, which will result in regression of dysplastic lesions. Studies have shown dietary intervention and nutrient supplementation to be effective in preventing cervical cancer. Additionally, local escharotic treatment combined with systemic treatment shows significant potential in reducing dysplasia. Recent advances in vaccination technology demonstrate the effectiveness of an HPV vaccine. The vaccine, however, may have many social and cost-prohibiting limitations, as well as health side effects. (+info)
HPV infection and number of lifetime sexual partners are strong predictors for 'natural' regression of CIN 2 and 3.
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The aim of this paper was to evaluate the factors that predict regression of untreated CIN 2 and 3. A total of 93 patients with colposcopic persistent CIN 2 and 3 lesions after biopsy were followed for 6 months. Human papillomavirus (HPV) types were determined by polymerase chain reaction at enrolment. We analysed the biologic and demographic predictors of natural regression using univariate and multivariate methods. The overall regression rate was 52% (48 out of 93), including 58% (22 out of 38) of CIN 2 and 47% (26 out of 55) of CIN 3 lesions (P=0.31 for difference). Human papillomavirus was detected in 84% (78 out of 93) of patients. In univariate analysis, 80% (12 out of 15) of lesions without HPV regressed compared to 46% (36 out of 78) of lesions with HPV infection (P=0.016). Women without HPV and those who had a resolution of HPV had a four-fold higher chance of regression than those with persistent HPV (relative odds=3.5, 95% CI=1.4-8.6). Women with five or fewer lifetime sexual partners had higher rates of regression than women with more than five partners (P=0.003). In multivariate analysis, HPV status and number of sexual partners remained as significant independent predictors of regression. In conclusion, HPV status and number of lifetime sexual partners were strongly predictive of regression of untreated CIN 2 and 3. (+info)
Nicotine and cotinine in the cervical mucus of smokers, passive smokers, and nonsmokers.
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Although epidemiological studies suggest that cigarette smoking is a risk factor for cervical cancer, further evidence is required to document the biological plausibility of this relationship. This study obtained cervical mucus, using a cervical flush technique, from 50 patients in a neoplasia clinic. Nicotine was detected in the cervical mucus of all 25 smokers and cotinine in the mucus of 84% of the smokers; nicotine and cotinine levels were correlated (P < or = 0.10) with both the number of cigarettes usually smoked and the number smoked in the last 24 h. Nicotine and cotinine levels for passive smokers and nonexposed women were much lower than for women who currently smoked, with little difference found between the nonsmoking women who did and did not report passive smoke exposure. In the one woman who reported smokeless tobacco use, both nicotine and cotinine were detected at much higher levels than for other nonsmoking women. These results indicate that tobacco constituents do indeed reach the uterine cervix, suggesting that they could play a causal role in the development of cervical cancer. (+info)
General primer polymerase chain reaction in combination with sequence analysis for identification of potentially novel human papillomavirus genotypes in cervical lesions.
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We recently described the detection of potentially novel human papillomaviruses (HPV) genotypes (HPV types X [HPV X]) in cervical smears (A. J. C. van den Brule, C. J. L. M. Meijer, V. Bakels, P. Kenemans, and J. M. M. Walboomers, J. Clin. Microbiol. 28:2739-2743, 1990) by using the general primer-mediated polymerase chain reaction method (GP-PCR). In this study, the HPV specificities of GP-PCR products were determined by sequence analyses. M13 bacteriophage clones of PCR products derived from cloned unsequenced HPV genotypes 13, 32, 35, 43, 44, 45, 51, and 56 were subjected to dideoxy sequencing. Analyses of the putative amino acid sequences of these HPV types in addition to published HPV sequence data revealed stretches of highly conserved amino acid residues present in all HPV types, resulting in an HPV amino acid consensus sequence. Subsequently, HPV X-specific PCR products found in premalignant cervical lesions (n = 3), carcinomas in situ (n = 6), and invasive cancer (n = 6) were analyzed for their nucleotide sequences. Comparison of these sequences with published HPV nucleotide sequences and data obtained in this study revealed three HPV type 35, two HPV type 45, one HPV type 51, two HPV type 56, and six unique HPV X sequences, of which three types were present in four cases of carcinomas (in situ). The nucleotide sequences determined appeared to be unique after a data bank search. Furthermore, the sequences of all HPV X isolates matched the HPV amino acid consensus sequence, thus confirming HPV specificity. This study illustrates the power of GP-PCR in combination with sequence analysis to determine HPV specificity and genotyping of PCR products derived from sequenced as well as unsequenced HPVs, including novel, not yet identified HPV types. (+info)
Prevalence of genital human papillomavirus infection in Wellington women.
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OBJECTIVES: To determine prevalence of human papillomavirus (HPV) in Wellington women, to identify risk factors for HPV infection, to correlate presence of HPV with cervical cytology, and to identify characteristics of women infected with HPV but with normal cytology. DESIGN: Demographic, social, personal and clinical data were collected by a confidential self-administered coded questionnaire. The presence of DNA from HPV types 6/11, 16 + 18 and 31 + 33 in cervical scrapes was determined by dot-blot DNA hybridisation. All data were correlated with cervical cytology results. SETTING AND SUBJECTS: Two thousand and twenty one women attending family planning clinics in the Wellington region participated in the study. The mean age of participants was 26 years, 33.3% currently smoked, 72.3% used hormonal contraceptives, 31.4% were married, and 91.4% were of European origin. RESULTS: We found 10.9% of the study group infected with HPV. HPV types 16 and/or 18 predominated, being detected in 71.5% of HPV-positive women either alone or with other types. Of those infected 26.2% had multiple infections. Dysplasia (n = 87) or atypia (n = 84) were observed in 26.7% of infected women (n = 221) and 6.25% of uninfected women (n = 1792). Over 8% of women with normal smears were HPV positive, and types 16/18 were most common in these women. CONCLUSIONS: Women with cervical dysplasia or atypia were six times more likely to have HPV infection than other women. The main risk factor for HPV infection, particularly with types 16 and/or 18, was multiple (> 5) sexual partners in the last year independent of other variables. Multivariate analysis of data showed no independent association between HPV infection and ethnicity, educational background, smoking history, marital status, contraceptive use, age at first sexual intercourse, or number of lifetime sexual partners. (+info)
Detection of genomic amplification of the human telomerase gene (TERC) in cytologic specimens as a genetic test for the diagnosis of cervical dysplasia.
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Invasive cervical carcinomas frequently reveal additional copies of the long arm of chromosome 3. The detection of this genetic aberration in diagnostic samples could therefore complement the morphological interpretation. We have developed a triple-color DNA probe set for the visualization of chromosomal copy number changes directly in thin-layer cervical cytology slides by fluorescence in situ hybridization. The probe set consists of a BAC contig that contains sequences for the RNA component of the human telomerase gene (TERC) on chromosome band 3q26, and repeat sequences specific for the centromeres of chromosomes 3 and 7 as controls. In a blinded study, we analyzed 57 thin-layer slides that had been rigorously screened and classified as normal (n = 13), atypical squamous cells (ASC, n = 5), low-grade squamous intraepithelial lesions (LSIL, n = 14), and high-grade squamous intraepithelial lesions (HSIL) grade 2 (CIN2, n = 8), and grade 3 (CIN3, n = 17). The percentage of tetraploid cells (P(Trend) < 0.0005) and cells with multiple 3q signals increased with the severity of the cytologic interpretation (P(Trend) < 0.0005). While only few normal samples, ASC and LSIL lesions, revealed copy number increases of 3q, 63% of the HSIL (CIN2) lesions and 76% of the HSIL (CIN3) lesions showed extra copies of 3q. We conclude that the visualization of chromosome 3q copy numbers in routinely prepared cytological material using BAC clones specific for TERC serves as an independent screening test for HSIL and may help to determine the progressive potential of individual lesions. (+info)