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PubMed1996

Trends in cervical cancer mortality in South Africa.

BACKGROUND: Cervical cancer is an important cause of death throughout the world, especially in less developed countries. Reports of trends in cervical cancer mortality from less developed countries have been limited by poor data quality and inaccurate population estimates. This paper examines trends in cervical cancer mortality in South Africa from 1949 to 1990 and discusses the impact of cytology screening on these trends. METHODS: Analysis of national mortality statistics and reconstructed population data. RESULTS: The age-standardized mortality rates for Whites declined after the mid 1960s, while that for Coloureds rose, particularly before the 1970s. These trends were affected predominantly by trends among women in the 35-64 age range. CONCLUSIONS: The pattern of mortality in successive birth cohorts for Whites is consistent with a reduction in age-specific mortality following the advent of cytological screening. The same pattern is not evident in trends for Coloureds, among whom screening has apparently had a minor impact if any at all. The apparent lack of impact of screening in those groups of women most at risk of cervical cancer lends weight to demands for the implementation of equitable and rational screening programmes for cervical cancer in South Africa and internationally.

Adult↗
PubMed2005

Advances in the management of cervical cancer.

This review presents key advances in the management of cervical cancer. Traditionally, cervical cancer is staged clinically and has been treated either by radical hysterectomy or by radiotherapy. Improvements in imaging have led to more accurate therapeutic decision making and treatment planning. The evidence on fertility-preserving surgery for cervical cancer and chemoradiotherapy for locally advanced cancer is summarized here. An improved understanding of the viral aetiology of cervical cancer has led to the development of therapeutic vaccination, with limited success. There is increasing recognition of the psychosexual needs of women who have survived cervical cancer.

Combined Modality Therapy↗
PubMed1993

[Clinical application of extraperitoneal ovarian transposition in cervical cancer].

Ten young patients with cervical cancer were treated by extraperitoneal ovarian transposition. All patients received pelvic irradiation post operatively. Sex hormone were analysed after treatment. 10 cervical cancer patients who were irradiated only were analysed as control. Our data suggested that extraperitoneal ovarian transposition has definite significance for reserving ovarian function in young patients with cervical cancer and improve the quality of operation. This operation is chiefly suited for young patients with early cervical cancer who were operated extra-peritoneally, also for young patients who are irradiated alone or before operation.

Adult↗
PubMed2006

[Cervical cancer prevention: the impact of HPV vaccination].

Cervical cancer remains a critical public health problem that is second only to breast cancer in overall disease burden for women throughout the world. In spite of the success of cervical cancer screening, Pap cytology screening is yet to be effectively implemented or has failed to reduce cervical cancer rates to an appreciable extent. Screening appears to benefit only a small fraction of women although a much larger percentage endures the inconvenience of the Pap test in order to avoid cervical cancer. The establishment of Human Papillomavirus (HPV) infection as the necessary cause of cervical precancers and cancers provides a tremendous opportunity for cervical cancer prevention through vaccination. HPV 16 and 18 which cause 70% of cervical cancers worldwide. Thus a prophylactic vaccine to prevent HPV related precancerous lesions and cancers would save lives, reduce the need for costly medical procedures and provide both women and communities throughout the world with substantial benefits. Based on the induction of neutralizing antibodies by non infectious Virus Like Particles (VLP) of L1 capside protein, prophylactic HPV vaccines have consistently induced high titter of neutralizing antibodies with minimal side effects and induce more than 90% protection from persistent HPV 16-18 infection and HPV 16 and 18 associated high-grade Cervical Intraepithelial Neoplasia (CIN) in proof of concept efficacy trials. HPV 16-18 vaccination will prevent HPV16-18 incident infection, and subsequently decrease in 90% the frequency of abnormal Pap attributable to these types and in about 50% overall abnormal Pap. HPV vaccination will reduce the number of women who require colposcopy, biopsy and cervical treatment for precancerous cervical lesions. The level of protection from death due to cervical cancer could exceed 95%. Three large phases prophylactic HPV VLP trials are now in progress and will form the basis for licensing of candidate vaccines in 2006. HPV vaccination targeting young female adolescents, aged 11 to 16 years, with a catch-up of those aged 17-25 years, would be a strategy to be addressed. Cervical cancer screening strategies, that will be cost-effective for the proper surveillance of women protected by HPV vaccination, are under analysis.

Adolescent↗
PubMedDate not supplied

Barriers to cervical cancer screening in rural Mexico.

Cervical cancer is a major health problem in Mexico. The national mortality rate due to cervical cancer was estimated at 21.8 per 100,000 among women over 15 years of age in 1994. Reasons for this high prevalence have not been defined, although it may be influenced by lack of access to health care, lack of knowledge about the Pap procedure, or cultural beliefs. While some studies have examined barriers to Pap screening, most have focused on urban samples. We conducted a pilot study using direct interviews to learn about factors that may influence cervical cancer screening among rural Mexican women. We interviewed 97 rural women between the ages of 16 and 66 and found that 52% had not received a Pap smear within the last 2 years (of that group, 62% had never received a Pap smear). In our sample, the most frequent reason for not obtaining a Pap smear was anxiety regarding physical privacy (50%). Less frequent reasons were lack of knowledge (18%) and difficulty accessing health care (14%). Women who had delivered children were significantly more likely to have received a Pap smear (71%) than women who had no children (10%), P < 0.05. The responses of many women suggest that compliance with cervical cancer screening would be enhanced by addressing cultural beliefs, encouraging conversations about women's health issues, and increasing the number of female health care providers.

Adolescent↗
PubMed2005

Clinical potential of inhibitors of survival pathways and activators of apoptotic pathways in treatment of cervical cancer: changing the apoptotic balance.

Cervical cancer is the most common gynaecological malignant disorder worldwide. The best possible treatment of locally advanced cervical cancer is a combination of radiation and cisplatin-based chemotherapy. However, 5-year overall survival is still only 52%. To improve treatment results, research should focus on the discovery of innovative drug strategies. Drugs directed at inducing tumour-cell apoptosis are regarded as important treatment modalities. Here, we present an overview of the molecular options that can change the apoptotic balance in cervical cancer, through increasing death-receptor-mediated apoptosis, the use of proteasome inhibitors, short interfering RNAs, or non-steroidal anti-inflammatory drugs (NSAIDs). Furthermore, the potential of attacking prosurvival signalling through the epidermal-growth-factor receptor and insulin-like-growth-factor receptor to support the apoptotic process is discussed. Additional research is needed to elucidate the clinical potential of these compounds in the treatment of cervical cancer.

Antineoplastic Agents↗
PubMed2003

TAP1, TAP2, and HLA-DR2 alleles are predictors of cervical cancer risk.

OBJECTIVE: The likelihood of developing cervical cancer has been shown to be increased in persons with certain HLA alleles. We evaluated immune response genes in the HLA region of chromosome 6 to see if individual or interactive associations with cervical cancer risk could be identified. METHODS: Tissue was obtained from 127 women undergoing surgical treatment for cervical cancer. Blood samples were obtained from 175 control subjects. A combination of polymerase chain reaction (PCR), sequence-specific PCR, and DNA sequencing was used to evaluate polymorphic alleles, including HLA class I B7, TNF alpha, HLA class II DR2, TAP1, and TAP2 genes. Fisher's exact test and logistic regression modeling were used for statistical analysis. RESULTS: A significantly greater proportion of the patients with cervical cancer were found to have the HLA class II DR2 1501 allele (P = 0.023) and the TAP2 A/B heterozygous pattern of alleles (P = 0.0006) than were women without cervical cancer. A proportion of patients with cervical cancer significantly smaller than that of the control women had a polymorphism at the -238 position of the TNF promoter and the TAP1 C/C homozygous pattern of alleles. With logistic modeling, the markers that showed consistent association with the occurrence of cervical cancer were TAP2 A/B, HLA-DR2 1501, and TAP1 C/C. CONCLUSIONS: We demonstrated a significant association between immune response genes and the risk of cervical cancer. Our data create a compelling argument for a gene or a cluster of genes in the HLA region of chromosome 6 that regulates host immune responses to human papillomavirus infection in a manner that results in inherited susceptibility or resistance to the transforming properties of oncogenic papillomaviruses.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Functional analysis of bladder cancer-related protein gene: a putative cervical cancer tumor suppressor gene in cervical carcinoma.

Our previous study has suggested thatthe bladder cancer-associated protein gene (BLCAP) was among the differentially expressed genes in cervical cancer. We confirm here that BLCAP is expressed in all noncancerous cervical tissues (10/10), but it is greatly lost in primary cervical cancer tissue (31/39). In order to further investigate the functional roles of BLCAP, we stably transfected BLCAP cDNA into HeLa cells. The HeLa cells expressing BLCAP show reduced cell growth and clone genicity compared to the vector-transfected cognate cells. BLCAP expression in HeLa cells leads to growth arrest and significantly enhanced apoptosis in vitro and reduced tumor formation in vivo. Thus, BLCAP might be a potential tumor suppressor gene in cervical carcinoma.

Base Sequence↗
PubMed1995

Using central cancer-registry data to monitor progress in early detection of breast and cervical cancer (Illinois, United States).

Cases of breast and cervical cancer account for almost 40 percent of all cancers diagnosed in Illinois (United States) women. Information on screening rates, however, is not collected routinely for the populations at risk. This paper reports on surveillance indicators designed to identify target populations and evaluate programs. All cases of cancers of the breast (n = 38,824, including in situ) and invasive cervix (n = 2,763) with a known stage, among women aged 40 to 74, were identified through the population-based Illinois State Cancer Registry for 1986 to 1992. The proportion of breast cancer cases with in situ disease-stage and cervical cancer cases with a late invasive stage were selected as surveillance indicators. Differences by age and race were evaluated, as were age- and race-specific trends. The data suggest that Black women, aged 40 to 74 years, and White women, aged 65 to 74 years, should be targeted for breast-cancer-screening interventions. All women, aged 40 to 74, should be targeted for enhanced cervical-cancer-screening interventions. Significant trends in in situ breast cancer diagnoses were apparent in all age-race groups, however no significant decline in invasive cervical cancer was found for any age-race group. The indicators identified the age- and race-specific disparities among potential target populations for breast and cervical cancer screening.

Adult↗
PubMed1999

Clinical significance of telomerase activation and telomeric restriction fragment (TRF) in cervical cancer.

Telomerase activation was examined in 50 cases of cervical cancer, 27 normal cervix and five cervical cancer cell lines using the sensitive polymerase chain reaction (PCR)-based TRAP (telomeric repeat amplification protocol) assay. Telomeric restriction fragment (TRF) length of these specimens was measured by Southern hybridisation. Telomerase activation was common in cervical cancers and was detected in 46/50 cases (92%). Telomerase activity was weak in normal cervix and was detected only in 2/27 cases (7.4%). Telomerase activity was detected in all stages of cervical cancer suggesting that it is an early event in cancer progression. The clinical significance of telomerase activation was analysed in 47 squamous cell carcinoma of the cervix. High telomerase activity was more frequently detected in advanced diseases (100% in stage III and stage IV cervical cancers combined) compared with early diseases (68.6% in stage I and stage II cancers combined). The difference was statistically significant (P < 0.02). Telomerase activity was not statistically correlated with other clinical parameters examined. This is the first report of telomeric length in human cervical cancer. Both shortening and elongation of TRF length in cervical cancers was observed. Advanced cervical cancers tended to have a wider range of variation of TRF length compared with early disease and normal cervix. There was no obvious relationship between TRF length and the clinical parameters examined including clinical staging, differentiation status of tumour, human papilloma virus (HPV) infection, recurrence rate, tumour size and invasion depth. The clinical significance of TRF length appears to be limited in cervical cancers. Our results indicate that telomerase activity is closely associated with tumour cells and may be useful as a marker for detection of tumour cells in cervical biopsies.

Adenocarcinoma↗
PubMed2006

[Cervical cancer screening: current status and perspectives].

Cervical cancer screening with Pap cytology has effectively reduced the incidence of morbidity and mortality from invasive cervical cancer. However, Pap cytology has important limitation and is not completely protective. Invasive cervical cancers are still diagnosed and main reasons are an insufficient coverage rate and presence of false-negative results. HPV testing has greater sensitivity than Pap cytology for detecting high-grade lesions and cancer and is clearly one of the most promising new screening tools. It has the potential to improve cervical cancer screening effectiveness. The aim of our study was to discuss the current situation of cervical cancer screening in Switzerland, limitations of Pap cytology as well as the benefice expected with HPV testing and vaccienes.

Europe↗
PubMed1993

[Hematometra in patients with cervical cancer--its CT presentation and clinical significance].

Cervical cancer is the most common gynecologic malignancy in Chinese. Clinical staging has been traditionally used in cervical cancer, according to international Federation of Gynecology and Obstetrics (FIGO) staging classification. Computed tomography was an adjunctive modality for detecting paraaortic lymph nodes in preoperative evaluation. But CT has failed to accurately define the extent of parametrial and vaginal invasion. Here, an attempt has been made to define indirect clues alerting to invasive cervical cancer. Hematometra can be seen in CT as a dilated uterine cavity with retention of significant fluid. The incidence of hematometra was 5% (5/101) in control group, and 26% (22/84) in cervical cancer. Hematometra cannot be more specific for cervical cancer, with an accuracy of 64%, sensitivity of 82% and specificity of 61%. Hematometra was found to have a statistically high relationship with high cancer staging and uterine invasion. The Chi-square values were 14.8 (P < 0.005) in high cancer staging, and 19.8 in uterine invasion. The accuracy of hematometra was 65% in high cancer staging, and 74% in uterine invasion. Hematometra was more common in postmenopause women, with accuracy elevated to 80% for uterine invasion. This is probably related to senile atrophy or endophytic growth of the cervix into the uterus as well as to hormone replacement. These were five false positive instances of hematometra, all unrelated to cervical cancer. They presented with marked fluid and a solid mass in the uterine cavity, and included endometrial adenocarcinoma, uterine myoma and leiomyosarcoma. None of cervical cancer showed a solid mass in a dilated uterine cavity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2005

The IARC commitment to cancer prevention: the example of papillomavirus and cervical cancer.

Every year approximately half a million women worldwide develop cervical cancer (CC) of whom 80% live in poor countries where population-based screening programmes are virtually non-existent. The role of sexually transmitted agents in the aetiology of cervical cancer has been suspected for more than a century, but knowledge in this field has rapidly expanded only in the last 20 years, after major improvements were made in detection methods for human papillomavirus (HPV). A dozen types of HPV have been identified in 99% of biopsy specimens from CC worldwide and the relative risk estimates for HPV in case-control studies of CC are in the 50 to 100 range. A meta-analysis done at the International Agency for Research on Cancer (IARC) included a total of 10,058 CC cases from 85 published studies. The most common HPV types identified in CC were, in order of decreasing prevalence, HPV 16, 18, 45, 31, 33, 58, 52, 35, 59, 56, 6, 51, 68, 39, 82, 73, 66 and 70. Over two-thirds of CC cases were associated with an infection of either HPV 16 (51.0%) or HPV 18 (16.2%). Despite the overwhelming importance of HPV, other factors contribute to the rare occurrence of CC after HPV infection. Nine case-control studies from the IARC have confirmed the adverse effect of long-term use of oral contraceptives, high parity, smoking and sexually transmitted infections (i.e. Chlamydia trachomatis and herpes simplex virus-2) after adjustment for, or stratification by, HPV infection. Ten surveys of HPV infection in population-based samples of approximately 15,000 women in four continents have shown that: (1) the prevalence of HPV infection varies greatly (between 2% and nearly 30%); and (2) the age distribution also varies widely, pointing to cohort effects. There is no effective medical treatment for HPV, but a prophylactic vaccine, based on late (L) 1 HPV 16 proteins, has been shown to be safe, highly immunogenic and efficacious in preventing persistent HPV infections. A multivalent vaccine against the most common oncogenic HPV types may thus ultimately represent the most effective way to prevent CC worldwide either alone, or in combination with screening. It may, however, take several years before this approach becomes a reality. Thus, early detection of CC precursor lesions by screening, and their treatment, will remain the most important measures for the control of CC for the foreseeable future.

Female↗
PubMed1991

Review on cervical cancer screening.

This article reviews literature of cervical cancer screening including the following topics: (1) basic conditions concerning screening; (2) consensus on cervical cancer screening; (3) some limitations and problems of cancer screening; (4) intervals of cervical cancer screening; (5) evaluation of cervical cancer screening; (6) methods for cervical cancer screening; (7) target population for screening (participants of both screening and rescreening); (8) selective screening (teenagers, pregnant women, prostitutes, hospital patients, clinic patients, immunosuppressive patients, and referral); (9) reports on screening programs in various countries; and (10) cost and benefit of screening.

Adolescent↗
PubMed2007

Impact of utilizing p16INK4A immunohistochemistry on estimated performance of three cervical cancer screening tests.

The histopathological diagnosis of cervical intraepithelial neoplasia grade 2,3 (CIN 2,3) is subjective and prone to variability. In our study, we analyzed the impact of utilizing a biomarker (p16(INK4A)) together with histopathology to refine the "gold standard" utilized for evaluating the performance of 3 different cervical cancer screening tests: cervical cytology, human papillomavirus (HPV) DNA testing and visual inspection with acetic acid (VIA). Cervical biopsies from 2 South African cervical cancer screening studies originally diagnosed by a single pathologist were reevaluated by a second pathologist and a consensus pathology diagnosis obtained. Immunohistochemical staining for p16(INK4A) was then performed. The estimated sensitivity of some cervical cancer screening tests was markedly impacted by the criteria utilized to define CIN 2,3. Use of routine histopathology markedly underestimated the sensitivity of both conventional cytology and HPV DNA testing compared to an improved gold standard of consensus pathology and p16(INK4A) positivity. In contrast, routine histopathology overestimated the sensitivity of VIA. Our results demonstrate that refining the diagnosis of CIN 2,3 through the use of consensus pathology and immunohistochemical staining for p16(INK4A) has an important impact on measurement of the performance of cervical cancer screening tests. The sensitivity of screening tests such as HPV DNA testing and conventional cytology may be underestimated when an imperfect gold standard (routine histopathology) is used. In contrast, the sensitivity of other tests, such as VIA, may be overestimated with an imperfect gold standard.

Cyclin-Dependent Kinase Inhibitor p16↗
PubMed1986

Epidemiology of uterine cervical cancer.

The epidemiology of cervical cancer presents a number of unique challenges, mainly with respect to disentangling correlated factors and to elucidating biological mechanisms. The available evidence suggests a complex multifactorial etiology, although the relative contributions of risk factors and their interactions remain obscure. Infectious agents are strongly suspected, but as yet not conclusively identified. It is also unclear whether there are subgroups of women or periods of life that are most susceptible to the action of infectious agents, and the contribution of the "male factor" needs to be defined. Several epidemiologic leads can be pursued through biochemical and molecular techniques. Most promising is the recent evidence linking certain HPV types to cervical abnormalities, including cancer, and newly developed probes can be incorporated into epidemiologic studies to evaluate an array of risk factors. Endocrine and metabolic assays may be helpful in clarifying the role of exogenous and possibly endogenous hormones. The effects of cigarette smoking may be further evaluated by studying constituents of tobacco smoke and their metabolites in cervical mucus. Finally, the relationship of diet to cervical cancer should be assessed by examining the levels of micronutrients, trace minerals, and other nutritional indices in body tissues and fluids, as well as through interview data. An understanding of cervical cancer etiology will require a better identification of risk factors for precursor lesions as well as factors that enhance their progression to invasive cancer. Through studies that focus on disease stage and time-related events, it should be possible to clarify the multi-stage processes involved in cervical carcinogenesis, and those factors that may inhibit as well as promote transition rates. The protective effects of screening programs deserve further attention, and research into dietary factors may lead in time to nutritional intervention. Investigation by cell type should also be pursued to define the epidemiology of the rarely occurring adenocarcinomas and adenosquamous carcinomas of the cervix. Finally, preventive strategies should be targeted to high-risk populations, especially those of the lower socioeconomic classes and with limited access to medical care. The need for a renewed focus on epidemiology and prevention is emphasized by recent increases in exposure to several postulated risk factors, including sexual promiscuity, oral contraceptives, and smoking.(ABSTRACT TRUNCATED AT 400 WORDS)

Epidemiologic Methods↗
PubMed1996

Estimating the efficacy of screening by auditing smear histories of women with and without cervical cancer. The National Co-ordinating Network for Cervical Screening Working Group.

The screening histories of all 348 women with invasive cervical cancer diagnosed in 1992 in 24 self-selected district health authorities and health boards in England, Wales and Scotland were compared with those of 677 age- and residency-matched controls. The controls were randomly selected from the family health services authority (FHSA) register. Screening histories, comprising the dates and results of all smears taken before the date of diagnosis of the patient's cancer, were determined from the FHSA computer and laboratory records. We estimate that the number of cases of cervical cancer in participating districts in 1992 would have been 57% (95% confidence interval 28-86%) greater if there had been no previous screening. In women under the age of 70 it would have been approximately 75% (31-115%) greater. Extrapolation of the results from this pilot suggests that screening prevented between 1100 and 3900 cases of invasive cervical cancer in the UK in 1992. Women with stage 1B cancer or worse were more likely to have no record of previous screening than controls: 47% of these women under the age of 70 had been adequately screened according to current (5 yearly screening) guidelines, compared with 75% of matched controls. Thirteen per cent of all patients under age 70 had screening histories indicative of inadequate follow-up of smears requiring colposcopy. The proportion of microinvasive cases with screening predating diagnosis was similar to the proportion of controls. There was a strong correlation between stage and age: 56% of cancers in women under 35 were microinvasive compared with just 9% in women 65 years or over. The 'relative protection' following a negative smear was greatest in the first 12 months and fell off towards the end of the fifth year. These data suggest that full adherence to current guidelines could perhaps have prevented another 1250 cases, but additional steps would have been required to prevent some of the 2300 remaining cases in women under the age of 70.

Adult↗