Taking a stand against cervical cancer.
Help detect cervical cancer before it becomes difficult to treat. Here's how to encourage patients to get regular screening and to care for those with cancer.
Female↗
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Exploring the possibility of sexual-behavioural primary prevention interventions for cervical cancer.
Consistent causal and risk factors for cervical cancer indicate that primary prevention may be beneficial for cervical cancer prevention. However, social or behavioural primary prevention strategies are seldom discussed in the prevention literature. This paper uses thematic analyses of interviews with key informants involved with cervical cancer prevention policy development in New Zealand to explore the possibility of sexual-behavioural primary prevention. While many informants perceived primary prevention to be important, others were cautiously accepting or opposed to it. Many concerns were raised that highlighting a preventable (sexually transmitted) causal factor might lead to blame and stigma around cervical cancer and reduce participation in cervical screening. Much of the support for primary prevention depended on it being conducted (indirectly) in the context of young people's sexual health education. Positions on primary prevention appeared to be informed by common presumptions about what happens in the 'real world' and the commonality of human papilloma virus in the general population. We contend that the possible health benefits from sexual-behavioural strategies for cervical cancer primary prevention need further exploration.
Attitude to Health↗
Reflections on cervical cancer.
The incidence of invasive cervical cancer and consequently mortality decreased due to adequate screening programmes in Canada from 1969 to 2003. Systematic cervical screening programmes similar to those in Europe should be implemented throughout Canada. The new techniques, including a liquid-based cytology, associated or not with identifying human papilloma virus (HPV), allow the best results in prevention and early diagnosis of cervical cancer and high-grade squamous intraepithelial lesions (HSIL). In the future a vaccine against HPV type 16 could reduce the incidence of cervical cancer worldwide.
Canada↗
[Medical and social implication of cervical cancer screening].
Invasive cervical cancer represents a major health problem in Romania. When there is a functioning screening network, the incidence of invasive lesions has a marked reduction, this program being the most successful cancer prevention program of all times. 80% of the actual incidence and mortality from this disease occurs in countries without an organized screening. A good infrastructure of the cytopathologist--practitioner relation must be achieved in order to reach the standard of early detection of the preinvasive cervical lesions.
Female↗
Screening HIV-infected women for cervical cancer in Thailand: findings from a demonstration project.
OBJECTIVES: Although cervical cancer is an AIDS-defining illness, few HIV-infected women are routinely screened for cervical cancer in Thailand. We screened HIV-infected women for cervical cancer as a component of HIV care and assessed high-risk human papillomavirus (HPV) and cervical cancer prevalence. METHODS: From July 2003 through February 2004, HIV-infected women attending either an infectious disease clinic or a sexually transmitted infection (STI) clinic in Bangkok were tested for high-risk HPV types by Hybrid Capture 2 and screened for cervical cancer by Pap test; those with abnormal cervical cytology were referred for diagnosis and treatment. RESULTS: Two hundred ten HIV-infected women at an infectious disease clinic (n = 150) and an STI clinic (n = 60) received cervical cancer screening. The high-risk HPV prevalence was 38.6% and the prevalence of abnormal cervical cytology was 20.4%. Abnormal cervical cytology and high-risk HPV detection were associated (P < 0.001). We received pathology reports for 23 (53.5%) of 43 women, including all those with a Pap test showing high-grade squamous intraepithelial lesions; the cervical cancer prevalence was 1.9% (4 of 210; 95% confidence interval, 0.5-4.8%). CONCLUSION: The estimated prevalence of high-risk HPV and cervical cancer among HIV-infected women in Thailand was high. This emphasizes the need to integrate cervical cancer screening into HIV care.
Adult↗
[Epidemiological study on risk factors of cervical cancer].
The relationship between cervical cancer and risk factors including virus infection of cervix was studied with methods of molecular and serological epidemiology. DNA extracted from cervical biopsies taken from 57 cases and 51 controls were tested for HPV6/11, HPV16/18 by Dot-blot hybridization and for HSV-2 by PCR. Sera were detected for HCMV-IgM by ELISA. The results and risk factors were analyzed by logistic regression model. The multiple logistic regression model results showed that HPV16/18 infection was an important risk factor, the infection rate was significantly higher in the group of cervical cancer, the OR was 31.96. Other risk factors were the educational level and the number of birth, the OR were 0.57 and 1.85, respectively. The difference of HSV-2 infection of cervix and HCMV-IgM in serum was not significant between the two groups.
Case-Control Studies↗
Family physicians' knowledge of risk factors for cervical cancer.
BACKGROUND: A woman's risk for cervical cancer has been used by physicians to guide the initiation and frequency of a Pap smear. The aim of this study was to determine family physicians' knowledge of risk factors for cervical cancer and perceived importance of risk in screening women. METHODS: The self-administered questionnaire was mailed to 5000 randomly selected active members of the American Academy of Family Physicians (AAFP). RESULTS: Data from 2748 usable questionnaires indicated the mean number of risks considered for cervical cancer was 4.5. Physician's age and the number of reported risks were inversely correlated (p = 0.0001). Female physicians reported significantly more risk factors than male physicians (p = 0.05). The number of Pap smears performed per month was positively correlated with the number of risk factors reported (p = 0.001). Only 10% of the physicians indicated that they perform a Pap smear at the same interval regardless of the risk of the woman. CONCLUSIONS: This sample of family physicians has a limited understanding of the risk factors for cervical cancer. This was true regardless of the age, gender, training, race, geographic location, or practice setting of the responding physician. Yet the usual practice of screening for cervical cancer reported by these physicians would suggest that knowledge and use of risk factors would be a critical aspect of screening for cervical cancer.
Clinical Competence↗
Early non-invasive diagnosis of cervical cancer: beyond Pap smears and human papilloma virus (HPV) testing.
Cervical cancer is a major gynecologic malignancy around the world. However, current diagnostic methods such as Pap smear and human papilloma virus (HPV) testing are insufficient for an early diagnosis of cervical cancer, follow-up on therapy efficacy or to identify the women who might progress to cervical cancer (only about 1-5% of the HPV-positive women will develop cervical cancer). Patients with atypical squamous cells of undetermined significance (ASC-US) clearly need a better screening test. Developing a non-invasive method for early diagnosis of cervical cancer is essential. Our in vitro and translational research data support the hypothesis that: 1. Squamous cell cervical cancer is related to specific upregulation of tissue and serum Insulin-like Growth Factor-II levels (IGF-II; 100% sensitivity and 100% specificity). Serum IGF-I, but not IGF-II levels are elevated in other gynecological, breast, lung and prostate cancers. Serum IGF-II test helps in diagnosing cervical cancer as early as ASC-US or cervical intraepithelial neoplasia (CIN)-I and in monitoring therapy efficacy (p < 0.001 by Student's 't' test and Chi-square analysis). 2. Concomittant to increased serum IGF-II levels, IGF-Binding Protein 3 (IGF-BP3) levels are significantly decreased in persistent CIN and cervical cancer (p < 0.0001). As IGF-BP3 modulates IGF-II biological activity, significantly decreased serum IGF-BP3 levels (levels normalize after therapy; p < 0.001) may indicate a poor prognosis. Similar to serum IGF-II, serum IGF-BP3 levels help monitoring therapy efficacy in cervical cancer and advanced CIN. Measurement of serum IGF-II levels will help in early diagnosis of cervical cancer and monitoring of therapy outcome. Serum IGF-BP3 in conjunction with IGF-II levels may help in predicting prognosis as well as monitoring therapy efficacy.
Carcinoma, Squamous Cell↗
Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression.
BACKGROUND: Cervical Cancer (CC) exhibits highly complex genomic alterations. These include hemizygous deletions at 4p15.3, 10q24, 5q35, 3p12.3, and 11q24, the chromosomal sites of Slit-Robo pathway genes. However, no candidate tumor suppressor genes at these regions have been identified so far. Slit family of secreted proteins modulates chemokine-induced cell migration of distinct somatic cell types. Slit genes mediate their effect by binding to its receptor Roundabout (Robo). These genes have shown to be inactivated by promoter hypermethylation in a number of human cancers. RESULTS: To test whether Slit-Robo pathway genes are targets of inactivation at these sites of deletion, we examined promoter hypermethylation of SLIT1, SLIT2, SLIT3, ROBO1, and ROBO3 genes in invasive CC and its precursor lesions. We identified a high frequency of promoter hypermethylation in all the Slit-Robo genes resulting in down regulated gene expression in invasive CC, but the inhibitors of DNA methylation and histone deacetylases (HDACs) in CC cell lines failed to effectively reactivate the down-regulated expression. These results suggest a complex mechanism of inactivation in the Slit-Robo pathway in CC. By analysis of cervical precancerous lesions, we further show that promoter hypermethylation of Slit-Robo pathway occurs early in tumor progression. CONCLUSION: Taken together, these findings suggest that epigenetic alterations of Slit-Robo pathway genes (i) play a role in CC development, (ii) further delineation of molecular basis of promoter methylation-mediated gene regulation provides a potential basis for epigenetic-based therapy in advanced stage CC, and (iii) form epigenetic signatures to identify precancerous lesions at risk to progression.
DNA Methylation↗
Cervical-vaginal flora of women with invasive cervical cancer.
The cervical-vaginal flora of 21 women with invasive cervical cancer was determined. The cultures yielded polymicrobial growth with anaerobic organisms predominating. As compared with other studies of vaginal flora, the cancer patients were found to have a decreased frequency of isolation of aerobic lactobacilli, Staphylococcus epidermidis, and enterococci, and an increased frequency of isolation of Escherichia coli and Bacteriodes species. The composition of the anaerobic vaginal flora in these patients is similar to that described for immunosuppressed renal transplant patients.
Adult↗
Response to "Primary cervical cancer screening by self-sampling of human papillomavirus DNA in internal medicine outpatient clinics", by Dannecker et al. (Ann Oncol 2004; 15: 863-869) and "Histopathological validation of the sentinel node concept in cervical cancer", by Barranger et al. (Ann Oncol 2004; 15: 870-874): DNA microarrays will be instrumental in the future diagnosis of cervical dysplasia and neoplasia.
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Ambulatory Care Facilities↗
Prospects for controlling cervical cancer at the turn of the century.
Cervical cancer morbidity and mortality have decreased substantially during the last 50 years mostly due to successful organized or opportunistic screening with Pap cytology in high and middle income countries. In many low income countries Pap cytology screening is yet to be effectively implemented or has failed to reduce cervical cancer rates to an appreciable extent. The fact that infection with certain human papillomavirus (HPV) types is now recognized as a necessary cause of this disease has led to new research fronts on prevention of cervical cancer. Testing for HPV DNA has shown great promise as a screening tool with better sensitivity but somewhat lower specificity than Pap cytology. In combination with the latter, HPV testing has the potential to improve the negative predictive value of cytology, thus allowing for increased testing intervals, which would lower program costs with acceptable safety. Advances in cytology processing and automation have also led to new screening approaches that are increasingly gaining acceptance in high and middle income countries. For low income countries, visual inspection with acetic acid has proven to be an effective alternative to conventional Pap cytology, especially in settings where no screening programs have been implemented. Concerning primary prevention of cervical cancer, recent research on the safety and efficacy of candidate prophylactic vaccines against HPV have shown very promising results with nearly 100% efficacy in preventing persistent infections and development of cervical cancer precursors. However, policy makers are strongly cautioned to avoid deferring decisions concerning the implementation of cervical cancer screening under the expectation that a successful vaccine could obviate the need for secondary prevention strategies. This paper is available too at: http://www.insp.mx/salud/index.html.
Female↗
Assessment of chromosome 8 copy number in cervical cancer by fluorescent in situ hybridization.
Cervical carcinoma is a malignancy which typically occurs at the transformation zone between squamous and glandular epithelium. The vast majority falls into two histologic types, squamous cell and adenocarcinoma. In an effort to identify a subset of cervical cancer characterized by chromosome 8 trisomy, a biomarker extensively explored by this laboratory, we conducted a study of formalin-fixed, paraffin-embedded materials of cervical cancer. A total of 24 cases of cervical cancer were identified from the archives of the Rhode Island Hospital. Fluorescent in situ hybridization (FISH) using a chromosome 8 centromere enumeration probe was conducted to assess the chromosome 8 copy number in these specimens. Hybridization signals were scored among tumor cells in a blinded fashion. Tumors with >/=15% of cells with three signals were scored as trisomic. Of 24 cases studied, 23 were informative. Of the 23 informative cases, 12 (52.2%) were found to be trisomic. Eleven cases (47.8%) were disomic. The frequency of trisomy in a control chromosome 17 probe was 13.0% (3/23). Selected clinicopathologic characteristics of the tumors were also reviewed. The frequency of trisomy 8 among cases of invasive squamous cell carcinoma was 44.4% (8 of 18 tumors) and that of invasive adenocarcinoma was 80% (4 of 5 tumors). The sole tumor which was both trisomic 8 and amplified for the HER-2/neu oncogene was found to be an invasive adenocarcinoma. While the sample size in this pilot study is not large, the data obtained thus far clearly demonstrate that FISH is an appropriate technique for detecting chromosomal trisomies and that a subset of cervical cancer exists that is characterized by chromosome 8 trisomy. Further exploration of this biomarker is warranted.
Adenocarcinoma↗
Comparative analysis of invasive cervical cancer incidence rates in three Appalachian states.
BACKGROUND: Invasive cervical cancer (ICC) rates remain elevated in the Appalachian region of the United States. We investigated patterns of invasive cervical cancer incidence rates in three Appalachian states (Kentucky, West Virginia, Pennsylvania) to uncover specific high-risk subgroups within this large and heterogeneous region. METHODS: The analysis was conducted for the three states combined and individually. Invasive cervical cancer rates were characterized by individual and county-level sociodemographic variables, including age, race, poverty, education, Appalachian status, and rural/urban status. Bivariate analyses and multivariable Poisson regression models were conducted to address the relative contributions of each variable to the risk of invasive cervical cancer. RESULTS: The three states differed in the contribution of each factor to the risk of invasive cervical cancer. The overall invasive cervical cancer incidence rates for Kentucky, West Virginia, and Pennsylvania were 13.4, 13.9, and 10.2 per 100,000/yr, respectively. After controlling for other demographic variables, the effect of Appalachian status on invasive cervical cancer was weaker, while rural status, education, and race were stronger, significant predictors. CONCLUSIONS: This study illustrates the heterogeneity of population demographics and invasive cervical cancer risk, and the need to identify subregions and subgroups within Appalachia at highest risk for this disease.
Adult↗
Oral and cervical temperatures as marker variables for chronoradiotherapy of patients with cervical cancer.
Oral and cervical temperatures were measured every 30 min during the time the patients were awake (0800-2200) and hourly during the night in 28 women with stage II-III cervical cancer. Data series averaged over all patients were analyzed to determine the circadian rhythmic pattern of temperatures from both sites as well as of the difference in temperature between the two sites. The characteristics of the 24-hr component, notably the amplitude-acrophase pair, were found to differ between the two sites (P less than 0.001). Harmonics of the 24-hr component were found to contribute with statistical significance to the circadian waveform. Accordingly, the acrophase is compared to the macrophase (time of maximal value) and orthophase (time of maximal value assumed by a multiple component model). The relative merits of these different endpoints should be assessed as a function of clinical outcome.
Body Temperature↗
Chemotherapy of cervical cancer.
Chemotherapy of cervical cancer is a difficult problem. The cancer is chemosensitive but the ability to express that chemosensitivity may be modified by previous radiotherapy and inadequate renal function. Regimens are available which will produce remissions with increase in survival in patients with advanced disease. The use of cisplatin-containing regimens is limited to a select group of patients in whom renal function is adequate. Details of recommended regimens have been given within this chapter. When all else has failed, bromocriptine 2.5 mg twice daily may produce long remissions but unfortunately only in a small percentage of patients. In the future chemotherapy will be used more frequently in the initial management of the patient prior to potentially curative surgery or radiotherapy in the hope of improving overall survival.
Antineoplastic Agents↗
Combined-modality therapy of locally advanced cervical cancer.
Six randomized trials of chemoradiotherapy in cervical cancer have demonstrated improvement with cisplatin-based chemoradiotherapy compared with radiation alone or radiation with hydroxyurea. Only one randomized trial (Gynecologic Oncology Group [GOG] 120) compared different cisplatin-based regimens and demonstrated significantly more hematologic and gastrointestinal toxic effects with the combination of cisplatin, fluorouracil, and hydroxyurea than with weekly cisplatin alone. The use of fluorouracil and mitomycin as radiation sensitizers for cervical cancer is based on their activity in chemoradiotherapy for anal carcinoma. However, a three-fold increase in serious late bowel toxicity was seen in patients treated with fluorouracil and mitomycin compared with fluorouracil alone when combined with radiation therapy for cervical cancer. Another randomized trial demonstrated improvement in survival with fluorouracil infusion compared with radiation alone only in early-stage disease. However, the most recently completed randomized trial by the GOG, which compared continuous fluorouracil infusion with weekly cisplatin, was closed when interim analysis demonstrated no potential superiority to the fluorouracil arm. Uncontrolled studies have evaluated the use of carboplatin on several different schedules, but no controlled trials have yet been performed. In metastatic and recurrent cervical cancer, a number of newer agents, including paclitaxel, gemcitabine, topotecan, and vinorelbine, have demonstrated modest single-agent activity and even greater activity in combination with cisplatin. An expanding series of trials will define the role of these new agents combined with cisplatin and radiation therapy for locally advanced cervical cancer. The potential role of biologic agents in combination with chemoradiotherapy also needs to be examined in locally advanced cervical cancer.
Antineoplastic Combined Chemotherapy Protocols↗
Better late than never: reflections on the delayed prioritization of cervical cancer in international health.
Cervical cancer has disproportionately affected the world's most vulnerable women for generations, yet only recently has the disease become an international health priority. Using ethnographic evidence from a study in Iquitos, Peru, I identify three factors that have contributed to a historic blind spot regarding cervical cancer in underdeveloped regions: (a) transition theories predicting the emergence of cancer with increasing societal development, (b) chronic vs. infectious disease categories that miss the significance of infectious-associated cancers, and (c) dependence on epidemiologic statistics from underdeveloped regions for determining health care priorities. Implications for theory and education are discussed.
Attitude to Health↗