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PubMed2001

The role of human papillomavirus in screening for cervical cancer.

PURPOSE: To review the options for effectively screening for cervical cancer, including human papilloma virus (HPV) identification, cytologic screening, colposcopy, or a combination approach. Current pathophysiology, diagnostic criteria, treatment approaches, and patient preparation and education related to cervical cancer screening and prevention are also included. DATA SOURCES: Comprehensive review of current literature, including research and review articles. CONCLUSION: Because the Papanicolau (Pap) smear is a screening tool, not a diagnostic tool, further studies must be done to identify the actual nature of discovered abnormalities. Of particular concern is the classification of atypical squamous cells of undetermined significance (ASCUS), which may simply indicate inflammation, or may be the first indicator of serious pathology. Following ASCUS Pap smears with HPV screening will allow for a clarification of the best approach to treatment. A screening algorithm supported by a review of the literature is proposed. IMPLICATIONS FOR PRACTICE: Cervical cancer is a preventable disease caused by certain forms of HPV. Current screening protocols are based on the use of the Pap smear; and in areas where this test is routine and available, morbidity and mortality rates have dropped dramatically. Many women throughout the world and in underserved regions of the U. S. do not have adequate access to routine screening with Pap smear technology. As long as women continue to die needlessly of cervical cancer, more comprehensive and accessible screening methods must be explored. (Cutting the unnecessary worldwide and in the U. S.).

Adult↗

PubMed2005

[Significance of pelvic lymph node human papillomavirus DNA detection in cervical cancer].

OBJECTIVE: To assess the significance of human papillomavirus (HPV) DNA detection in the pelvic lymph nodes in cervical cancer. METHODS: HPV L1 gene fragment was amplified by HPV-specific PCR with general consensus primers from cervical cancer tissues. The types of HPV were identified by sequencing of the PCR product. The relationship between HPV positivity and pathological findings in metastatic pelvic lymph nodes of cervical cancer was analyzed. RESULTS: The positivity rate of HPV DNA was 40% in the pelvic lymph nodes in 40 cases of cervical cancer. HPV DNA was detected in the pelvic lymphatic nodes of all the 10 cases with pathologically confirmed lymph node metastasis of cervical cancer. HPV18 was detected in both of cervical and pelvic lymph nodes in some cases. CONCLUSIONS: HPV DNA can be detected in the pelvic lymph nodes before pathological identification of lymph node metastasis and indicates early pelvic lymph node metastasis of cervical cancer. The presence of HPV18 often indicates high likeliness of lymph node metastasis and suggests poor prognosis of the patients.

Base Sequence↗

PubMed1999

Predictors of compliance with recommended cervical cancer screening schedule: a population-based study.

BACKGROUND: The prevalence of routine cervical cancer screening and compliance with screening schedules are low compared to the Year 2000 objectives. Identifying predictors of routine screening and screening schedule compliance will help achieve these objectives. METHODS: We analyzed data from probability samples of 1,609 Missouri women responding to both the 1994 Behavioral Risk Factor Surveillance System (BRFSS) and the Missouri Enhanced Survey (ES). We generated prevalence odds ratios to identify predictors of non-compliance to cervical cancer screening guidelines. Also, among a sample of women reporting a reason for last Pap test, we estimated the relative odds of a screening v. diagnostic exam. RESULTS: In the combined probability sample, compliance with screening schedule was likely among women younger than 50 years of age and women who had either a recent mammography or a clinical breast exam. Being African-American, not experiencing a cost barrier when seeking medical care, having at least a high-school education and health coverage were each associated with an increased compliance with a screening schedule in the combined probability sample. Among women in the combined probability sample, whites, those who experienced no cost barrier to seeking medical care, the non-obese, and those who had a recent mammography were each more likely to have had a screening as opposed to a diagnostic exam. DISCUSSION: Cancer control and cardiovascular (CVD) prevention programs should consider jointly targeting those at high risk for cervical cancer and CVD because of aging and associated high-risk behavior such as non-compliance with cervical cancer screening, smoking, and obesity. Also, further research is needed to examine whether the increased compliance with cervical cancer screening guidelines among African American women may be in part due to higher occurrence of diagnostic Pap smears.

Adult↗

PubMed2006

[Prognostic factors of uterine cervical cancer].

The large majority of gynecologic malignancies are comprised of uterine cervical cancer, endometrial cancer and ovarian cancer. Prognostic factors for each disease are based on various clinical pathological features, including clinical stage, tumor size, and lymph node metastatis for uterine cervical cancer. In addition to these factors, recent studies have investigated the role of various molecules including tumor markers and Hb level, apoptosis-related molecules as well as various genetic abnormalities as prognostic factor or indicators for uterine cervical cancer. This molecular background of uterine cervical cancer will shape future directions in the increasingly individualized basis of treatment.

Antigens, Neoplasm↗

PubMed2006

What happens when organization of cervical cancer screening is delayed or stopped?

OBJECTIVES: Many countries rely on opportunistic screening, and data on its effectiveness are asked for. We assessed the impact on cervical cancer incidence and mortality of opportunistic screening compared with organized screening. SETTING: Women aged 30-64 in Denmark, 1973-2002; 16 counties with different screening strategies. METHODS: Cumulative incidence and mortality rates for women aged 30-64 by county. Poisson regression of incidence and mortality rates by age, calendar period and county. Interaction between type of county and calendar period measured the difference between counties with screening organized early versus late in time. RESULTS: A statistically significant interaction was found between type of county and calendar period (P=0.0151) for cervical cancer incidence, but not for cervical cancer mortality (P=0.9593). The interaction terms were not statistically significant when a comparison was made between a single county in which an organized programme was interrupted for an 11-year period and other counties. There was, however, a statistically significant increased incidence and mortality rates at the restart of the organized programme. CONCLUSION: Organization of cervical cancer screening accelerated the decline in cervical cancer incidence, compared with the trend in areas relying on opportunistic screening. No impact could be measured of the screening organization on cervical cancer mortality. A decade long stop of an organized screening programme was associated with a temporary increase in cervical cancer incidence and mortality. Coverage remains a key quality indicator in the ongoing modernization of screening technology.

Adult↗

PubMedDate not supplied

Anti-cancer effect of adenovirus p53 on human cervical cancer cell growth in vitro and in vivo.

To evaluate anti-tumor effects of recombinant adenovirus p53, time-course p53, E6 expression, and cell growth inhibition were investigated in vitro and in vivo using cervical cancer cell lines such as CaSki, SiHa, HeLa, HeLaS3, C33A, and HT3. The cell growth inhibition was studied via cell count assay, MTT assay and neutral red assay. After transfecting AdCMVp53 into SiHa cells-xenografted nude mice, the transduction efficiency and anti-tumor effect were investigated for a month. The results showed that adenoviral p53 expression induced significant growth suppression on the cancer cells, in which E6 transcript was strongly repressed, and that the expression of p53 and E6 were remarkably dependent on each cell type. The transduction efficiency was highly maintained in vivo as well as in vitro, and the size of tumor was remarkably decreased in comparison with AdCMVLacZ control. The results suggest that the adenovirus-mediated p53 gene transfection was done very effectively in vitro and in vivo experiment, and the cell growth was suppressed via p53-dependent apoptotic cell death, and that the anti-tumor effect could be related to E6 and p53 expression pattern.

Adenoviruses, Human↗

PubMed1995

Development of a cervical cancer education program for native American women in North Carolina.

The North Carolina Native American Cervical Cancer Prevention Project is a five-year, NCI-funded public health education program. The project was developed to address the problem of excess mortality from cervical cancer among Native American women by increasing screening and follow-up of abnormal cervical smears. This paper describes the process of developing and implementing the intervention, an individualized health education program. Development of the intervention was guided by the health belief model, social learning theory, self efficacy theory, and PRECEDE, a planning model. Community analysis revealed that the target populations had limited awareness of cervical cancer as a specific type of cancer, and had an experientially-based pessimistic outlook regarding survival with cancer. Steps in developing the cervical-cancer prevention program included 1) development of objectives, 2) selection of strategies and development of cervical cancer education materials, 3) pretesting and revision, and 4) implementation, monitoring, and further revision. Native American lay health educators were recruited and trained to deliver the program. The experience of developing and implementing the individualized health education program suggests that the design of health education programs for Native Americans should begin with examination of basic assumptions regarding the nature of health and illness in the target population. The unique cultures and the diversity of Native American populations are critical factors in the development of health education programs for them.

Adolescent↗

PubMed1991

Invasive cervical cancer and intrauterine device use.

Although the hypothesis that intrauterine device (IUD) use might promote cervical cancer has been considered since the introduction of IUDs in the early 1900s, previous studies are inconclusive. Data collected in interviews with 481 invasive cervical cancer cases and 801 general population controls from Birmingham, Chicago, Denver, Miami and Philadelphia were used to address this issue. These data were analysed to determine the relationship between IUD use and the risk of cervical cancer, with consideration of the type of IUD (copper and inert) and duration of use. A non-significant reduced risk of cervical cancer was associated with copper IUD use, indicated by an adjusted odds ratio (OR) of 0.6 (95% Cl: 0.3-1.2), but virtually no effect was found for inert IUD use (OR = 1.1, 95% Cl: 0.9-1.7). Decreased risk with increased duration of copper IUD use supports a possible protective effect of copper IUD use on the development of invasive cervical cancer.

Adult↗

PubMed2000

Cervical cancer suppressor gene is within 1 cM on 6p23.

We previously showed loss of heterozygosity at 6p to be a common genetic alteration in cervical cancer and cervical intraepithelial neoplasia. To characterize this critical area of deletion in chromosome 6, we evaluated 107 invasive cervical cancers, using 23 polymorphic markers. Genomic DNA from microdissected frozen or paraffin-embedded cervical tumors and corresponding normal tissue was analyzed. Fifty-three percent (57/107) of the cervical tumors showed loss in 6p. Deletions were found in all stages and histologic types. Ninety-one percent (52/57) of these tumors had a loss at 6p23. One tumor defined the distal area of deletion at marker D6S429. Two tumors defined the proximal area of deletion at marker D6S1578. Genotyping of parental DNA was done on 16 cases to evaluate the origin of chromosomal loss. The deletion occurred in the paternal chromosome in 10 tumors and in the maternal in six. Within each tumor, the same parental chromosome was lost at all tested heterozygous 6p markers. The order of the polymorphic markers and estimate of distances in the critical region were confirmed by generation of a yeast artificial chromosome (YAC) contig and pulse-field gel electrophoresis. Our data strongly suggest that a gene important in cervical cancer tumorigenesis is located within a 1-cM region of 6p23, and it is not imprinted.

Adult↗

PubMed2000

Parametrial resection for invasive cervical cancer.

Removal of the parametrium represents the greatest technical challenge and is the main source of treatment related morbidity during radical surgery for carcinoma of the cervix. The move away from radical en bloc strategies, seen in breast and vulvar cancer surgery, has not taken place in cervical cancer; rather an increase of radicality has been advocated. One important reason is uncertainty about the pattern of lymphatic drainage in the parametrium, in particular the existence or absence of parametrial lymph nodes. According to classic anatomic studies and more recent lymphangiographic studies, the parametrium is viewed as a lymph collecting trunk interposed between the organ of drainage (the cervix) and the regional nodes located on the pelvic wall. In contrast to this view, studies in cervical cancer patients using the giant section technique have reported nodes that may be involved early in spread of cervical cancer and which are distributed randomly throughout the parametrium. Based on this observation a strategy of uncompromised radicality regarding parametrial resection has evolved in preference to an individualized strategy with the degree of radicality tailored according to the need for safe margins around the central tumor. This review presents an overview of current knowledge about the parametrium and a discussion about decision making regarding parametrial resection in cervical cancer.

Journal Article↗

PubMed1987

Conservation of E6 and E7 regions of human papillomavirus types 16 and 18 present in cervical cancers.

The E6 and E7 regions of human papillomavirus (HPV) type 16 were present in the DNA samples from cervical cancer cell lines, SKG-IIIa and SKG-IIIb, and those from cervical cancer tissues of three different patients. T601 cells, an NIH3T3 transformant obtained by transfection of DNA from a surgical specimen of a cervical cancer, also contained the E6 and E7 regions. The E6 region of HPV type 16 was expressed as mRNA in SKG-IIIa, SKG-IIIb and T601 cells. The E6 and E7 regions of HPV type 18 were present in the DNA samples from cervical cancer cell lines, SKG-I and SKG-II, and those from cervical cancer tissues of two different patients. SKG-I and SKG-II cells expressed the E6 region of HPV type 18 as mRNAs. These results strongly suggest that the E6 and E7 regions or the sequence surrounding these regions are important for maintaining malignant phenotype of cervical cancer cells.

Cell Line↗

PubMed2006

Review of cervical smears from 76 women with invasive cervical cancer: cytological findings and medicolegal implications.

OBJECTIVE: To review cervical smears from 76 women which were taken prior to the diagnosis of invasive cervical cancer and to determine the appropriateness of the cytology reports issued on the smears. METHODS: Cervical smears, clinical records, cervical smear history and cytology reports from 76 women with invasive cervical cancer were reviewed. After microscopic review of the cervical smears, the cases were divided into two groups: Group 1 comprised 50 women who were found to have had at least one false-negative (F/N) smear report prior to the diagnosis of invasive cervical cancer. Group 2 comprised 26 women for whom no evidence of F/N reporting was found. RESULTS: A total of 209 cervical smears from the 50 women in group 1 were available for review (range 2-12 smears per woman); 100 of the 209 smears were considered to have been reported appropriately. Ninety-seven smears which had been reported originally as negative or inadequate were found, on review, to contain numerous severely dyskaryotic cells and were reclassified as F/N smears. All of the 50 women had at least one F/N smear and 29 had two or more. Twelve smears from eight women contained only a few (<200 severely dyskaryotic cells). Forty women developed invasive squamous carcinoma and 10 developed invasive adenocarcinoma. The stage at diagnosis ranged from 1A to stage 4. Seventy-one smears from the 24 women in group 2 were available for review (range 1-15 smears per woman). In two cases included in group 2, no smears were provided for review as the smears had been lost or mislaid. Review of the 71 smears confirmed the accuracy of the original cytological classification of the smear. Nineteen women were diagnosed with squamous cancer, two microinvasive cancer, one glassy cell, two adenocarcinomas, and one with adenosquamous carcinoma. One women was found to have an embryonal rhabdomyosarcoma of the corpus uteri involving the cervix. DISCUSSION/CONCLUSION: The medicolegal implications are discussed in the light of the above findings. Evidence of breach of duty of care was presented in all 50 cases in group I although causation was not established in every case. There was no evidence of failure of duty of care in terms of the standard of the cervical cytology reports issued or standard of clinical management in 17 of the 26 cases in group 2. However, in seven of the 26 cases in group 2, clinical management of the case was substandard due to failure to investigate symptoms of irregular bleeding regardless of a negative cytology report (two cases), failure to act upon a suspicious smear report or consecutive inadequate smear reports (two cases), failure of follow-up after treatment of CIN3 (two cases) and histological misdiagnosis (one case).

Adult↗

PubMed2001

Interleukin-6 in cervical cancer: the relationship with vascular endothelial growth factor.

OBJECTIVE: Interleukin-6 (IL-6), a central proinflammatory cytokine, has been implicated in cervical cancer, though its role remains elusive. This study was an attempt to elucidate the role of IL-6 in the pathogenesis of cervical cancer, with particular emphasis on tumor angiogenesis. METHODS: Cytosolic IL-6, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) levels were determined via enzyme immunoassay in 60 FIGO stage IB-IIA cervical cancer patients. Immunohistochemical staining in tissue sections was performed to analyze the distributions of IL-6 and IL-6 receptors. Meanwhile, human papillomavirus (HPV) DNA was detected by polymerase chain reaction-based survey. In vitro studies of two cervical cancer cell lines, C33A and SiHa, for the interaction between IL-6 and VEGF were also performed. RESULTS: Consistently higher expression of IL-6 and VEGF was evident in cancerous tissues than in adjacent noncancer tissues in early-stage cervical cancer patients (P < 0.01). After recombinant human IL-6 was added, VEGF was induced in a time- and dose-dependent manner in cervical cancer cell line C33A. Correspondingly, interrupting the IL-6 autocrine machinery with either anti-IL-6 or anti-IL-6 receptor antibody markedly reduced the expression of VEGF at the transcriptional level in SiHa cells. Significantly higher levels of IL-6 in cancer tissues were observed in patients older than 45 (P < 0.01), patients with tumors >2 cm (P < 0.01), patients with oncogenic HPV-16 or -18 infections (P < 0.01), and patients with squamous cell carcinoma (P = 0.02). Patients with a deeper stromal invasion, vaginal invasion, lymphovascular emboli, or lymph node metastasis appeared to have higher intratumoral IL-6 levels, although the differences were statistically insignificant. CONCLUSIONS: Substantially high microenvironmental IL-6 levels promote tumor angiogenesis and the development of cervical cancer. Thus, inhibition of the biological activity of IL-6 may be potentially beneficial.

Adult↗

PubMed1995

Trends in cervical cancer incidence in the district of Florence.

The trend in cervical cancer incidence in the District of Florence from 1975 to 1989 was investigated. Tuscany Cancer Registry data were available since 1985. Incidence data from 1975 to 1985 were obtained through a retrospective survey of all the Departments of Pathology and Gynaecology in the district. Cytological screening for cervical cancer has been available in the district since 1973, and since 1980 active invitation of residents aged 25 to 59 years has been in use. A significant trend in decreasing incidence was evident for the overall population (P = 0.003) and for 40-49 (P = 0.028), 50-59 (P < 0.001) and 60-69 (P = 0.002) year age groups, whereas no significant trend was observed for the age group 30-39 years. An association between attendance to screening and reduced incidence was evident, in that a greater reduction was evident for those cohorts (ages 50-59 and 60-69) who had a higher compliance to screening 10-15 years before. If the decrease in cervical cancer incidence was spontaneous, a parallel decrease of CIN3, which is commonly assumed to be the precursor of invasive carcinoma, would be expected. On the contrary, the detection rate of CIN3 at first Pap test showed a significant increase in the study period. All these findings suggest that the observed reduction in cervical cancer incidence was mostly due to the effect of screening, and stress the need for optimising the coverage of the invited population.

Adult↗

PubMed1992

[Primary effect of preoperative intra-arterial infusion chemotherapy in cervical cancer].

In order to obtain better prognoses for cervical cancer, we conducted preoperative intra-arterial (i.a.) infusion chemotherapy of CDDP in combination with AT-II pressor. Two courses of i.a. chemotherapy were performed for 67 patients with cervical cancer in stage IIb containing 54 squamous cell carcinomas and 13 adenocarcinomas before operation every 3 weeks. A histologically desirable effect in cervical lesion was obtained. A group given preoperative i.a. chemotherapy had a significantly lower rate of infiltration beyond uterus in comparison with 156 patients with 145 squamous cell carcinomas and 11 adenocarcinomas treated by surgery alone as the control group. Further, the rate of histological infiltration to parametrial edges after i.a. chemotherapy tended to be lower than the control group. From the above, it was considered that preoperative i.a. infusion chemotherapy of CDDP in combination with AT-II pressor for cervical cancer was effective as a neo-adjuvant chemotherapy.

Adenocarcinoma↗

PubMed2001

Parity and Illiteracy as Risk Factors of Cervical Cancers in Viet Nam.

The aim of the present study was to examine the risk of cervical cancers with reference to multiparity and illiteracy in Ho Chi Minh City where this neoplasm is a very serious problem but no reports have documented its risk factors. The 5,034 cervical cancer cases treated from 1989-94 in the Central Oncology Clinic of Ho Chi Minh City were derived from published sources. The observed number of children born and the education level among cervical cancer cases were compared with those in the reference group, the general population based on the results of the national census in 1989 and the inter-census in 1994. Among cervical cancer patients, the number of children born was in a wide range from 1-20 children with the mean number being 6.6 children per patient. Most of the patients finished primary or some primary school (54.9%), followed by the illiteracy group (30.0%). Multiparity was found to increase the risk of cervical cancer (RR = 1.31, 95% CI = 1.30-1.32). Illiteracy was also found to be associated with an elevated risk (RR = 3.43, 95 % CI = 2.85-4.14). The significant increase in risk of cervical cancers linked to to multi parity and illiteracy is a very important finding in the south of Viet Nam, where cancer is a very serious problem and there is a lack of information on which to base primary and secondary prevention.efforts.

Journal Article↗

PubMed2004

Screening for HIV infection in women with newly diagnosed cervical cancer.

OBJECTIVE: This study aimed to investigate the prevalence of human immunodeficiency virus (HIV) infection in women with cervical cancer and to decide whether HIV testing should be included as part of the initial work-up of invasive cervical cancer. METHODS: This was a prospective case controlled study. Women with newly diagnosed cervical cancer were tested and age-matched women with benign gynecologic conditions were selected as control. Serum samples were tested for HIV I and HIV II antibodies at diagnosis and 3 months later. RESULTS: Two hundred twenty-five consecutive patients with newly diagnosed cervical cancer and two hundred twenty-three age-matched women with benign gynaecological conditions were tested. In comparison with the control, women with cervical cancer started sexual intercourse at an earlier age and had a statistically significant higher number of sexual partners. All the HIV tests were negative. The HIV prevalence rate was estimated to be 0.0-1.6% for both groups. CONCLUSION: HIV screening should not be a part of the initial work-up for cervical cancer in a population with a low background prevalence.

Adult↗

PubMed1996

Allelotyping of all chromosomal arms in invasive cervical cancer.

The best characterized factor in the development of cervical cancer is the integration, of human papillomavirus into cervical cell chromosomes. In addition to HPV integration, the neoplastic process probably requires the activation of cellular protooncogenes and loss of tumor suppressor gene function. Loss of heterozygosity analysis in a large sample is used to identify regions which harbor putative tumor suppressor genes (TSG) since the deletion of normal alleles unmask mutated alleles. We evaluated tumor tissue from invasive cervical carcinomas, carefully microdissected to eliminate normal stroma and lymphocytes, for LOH at all 41 chromosomal arms with 50 polymorphic markers. We have evaluated tumor and normal DNA pairs from 48 invasive cervical cancers of which 85% of the tumors are confined to the cervix. The mean loss for all chromosomal arms was 12%. Three regions exhibited LOH two standard deviations above the mean: 3p14.1-12 (40%), 11q23.3 (36%), and 6p22-21.3 (32%). Three regions showed loss one standard deviation above the mean: 19q13.4 (30%), 6q21-23.33 (25%), and 2q33-37 (24%). Our results indicate that a significant number of invasive cervical cancers have lost specific chromsomal regions, thereby suggesting that genes involved in the cell cycle regulation or the suppression of tumor development are located in these regions.

Alleles↗