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Downstaging of cervical cancer.

Globally cervical cancer is the fifth most common cancer and of estimated 460,000 new cases each year three quarters occur in developing countries. In India annually 16% of the world's total cases occur and only 5% are reported in the early stages. Downstaging is defined as a process of screening for cancer using clinical approaches for early detection of this disease. This is distinct from screening test and results in detection of the disease at a less advanced stage in the absence of screening. This experimental approach is applicable in developing countries where cytological screening is not possible in the near future. In this method paramedical staff trained for minimum period will be able to identify any abnormality including suspicious cervix and refer the case early to centres where facilities exist for treatment of premalignant and malignant lesions, including educating the women regarding risk factors, symptoms of the disease and prophylaxis. This experimental methodology recommended by WHO for developing countries like India has to be evaluated by monitoring various ongoing projects where visual inspection screening method is used. The results are collected which include feasibility, compliance, costing, referral methodology, difficulties in implementation, specificity, sensitivity, positive predictive value and drawbacks. The methodology of visual inspection and modified aided visual inspection, frequency and results of various studies in the Indian scenario is for recommendation of downstaging in MCH care. This is to be implemented in rural areas taking into consideration their cultural background and available infrastructure since cytology screening is not possible to cover even 20% of the existing cases in the near future.

Developing Countries↗

Serum retinol level and risk of subsequent cervical cancer in cases with cervical dysplasia.

We followed up on 134 women who had been diagnosed with cervical dysplasia to examine the relationship of dietary and serum vitamin A to subsequent cervical cancer. The subjects were women attending the Papanicolaou test screening for residents in Miyagi, Japan and histologically diagnosed as having cervical dysplasia between October 1987 and September 1988. Personal interviews were carried out, and blood samples were taken on the date of diagnosis of cervical dysplasia. The subjects were followed-up with cervical smear and colposcopy at about 3-month intervals from the date of interview until the end of February 1995. During the follow-up, 8 women (5.9%) developed cancer in situ or invasive cervical cancer and 106 (79.1%) reverted to normal. The rate of progression of the cancer in situ or invasive cervical cancer was 4.5 times higher in women with lower serum retinol levels than those with higher serum retinol levels (p = 0.08). The results suggest an association of low serum retinol level with development of cervical cancer.

Adolescent↗

Human papillomavirus and p53 polymorphism in Lithuanian cervical cancer patients.

BACKGROUND: Cervical cancer is the fourth most common cancer for women in Lithuania. One of the important cervical cancer risk factors is human papillomavirus (HPV) infection. Recent literature has considered p53 allelic polymorphism to be a putative predisposing factor for cervical carcinoma development. OBJECTIVE: The aim of this study was to elucidate the prevalence of HPV, especially HPV 16, in cervical cancer patients and in healthy women, to investigate the distribution of p53 gene 72 codon polymorphism and to correlate these to cervical cancer risk in Lithuanian women. METHODS: 588 women were included in the study: 212 women with primary diagnosed cervical cancer (case group) and 376 healthy volunteers (control group). RESULTS: A high prevalence of HPV DNA was detected in cervical cancer patients, 92.0%, and in control women, 23.6% (P < 0.0001). HPV 16 is the most frequent HPV type in cervical cancer patients. In the case of squamous cell carcinoma, this type was detected in 55.8%, in adenocarcinoma - 35.3%. In the control group, this type was detected in 19.0%. A statistically significant difference in the distribution of p53 alleles between the case and the control groups was found. CONCLUSIONS: Cervical cancer risk in Lithuanian patients is associated with HPV infection (OR = 75.39; 95% CI 33.61-192.98), especially HPV 16 type (OR = 100.3; 95% CI 46.05-238.59) and p53 homozygous Arg/Arg allele (OR = 2.10; 95% CI 1.10-4.19).

Adolescent↗

Acculturation and cervical cancer: knowledge, beliefs, and behaviors of Hispanic women.

In a community-based sample of Hispanic women, this study examines differences in relation to level of acculturation in knowledge about the Pap examination, fear/fatalism towards cancer, and cervical cancer screening behaviors. Respondents were randomly chosen from 11 churches in the Phoenix metropolitan area (n = 566) and were categorized into three acculturation levels: low (35.2%), bicultural (26.3%), and high (38.5%). Interviews focused on family history of cancer as well as knowledge about cancer and utilization of screening techniques for breast and cervical cancers. OLS regression and probit analyses were conducted to examine the role of acculturation in differentiating. Hispanic subgroups in relation to knowledge, beliefs, and behaviors regarding cervical cancer. Findings of the present study indicate that Hispanic women in the Phoenix metropolitan area are utilizing cervical cancer screening services with over 90 percent of women in all three acculturation groups ever having had a Pap exam and more than 50 percent having had the examination during the past year. However, results also indicate that of the Hispanic subgroups examined, lower acculturated Hispanic women have less knowledge about Pap smears and exhibit lower utilization rates for cervical cancer screening. These results suggest that lower-acculturated Hispanic women comprise the subgroup of Hispanics that is at greatest risk of presenting with advanced stages of cervical cancer. Results have implications for cancer screening and education programs for Hispanic women as well as implications for health care professionals who serve this population.

Acculturation↗

Candidate tumor suppressor, HCCS-1, is downregulated in human cancers and induces apoptosis in cervical cancer.

To identify the genes involved in cervical carcinogenesis, we applied the mRNA differential display method and identified a candidate tumor suppressor gene, HCCS-1, which was present in normal cervical tissue but absent in cervical cancer, metastatic lymph node and CUMC-6 cervical cancer cell line. HCCS-1 transcripts were expressed in many normal tissues including leukocyte, lung, spleen, liver, heart and uterine cervix. Its expression was absent in 8 human cancer cell lines. HCCS-1-transfected HeLa cells exhibited growth inhibition by about 50%. This inhibitory effect of HCCS-1 on cervical cancer cells was associated with apoptotic process including DNA fragmentation. HCCS-1-transfected HeLa cells were shown to release cytochrome c from mitochondria, which activates caspase-9 and -3 and finally results in cleavage of poly(ADP-ribose) polymerase. Apoptosis formation was detected by propidium-iodide/annexin V. HCCS-1-transfected HeLa cells were more sensitive to adriamycin or UVC ray triggered apoptosis. These results suggest that HCCS-1 is downregulated in multiple human tumor types and may serve as a candidate tumor suppressor gene through apoptotic pathway against human cervical cancer.

Amino Acid Sequence↗

Screening for squamous cervical cancer: duration of low risk after negative results of cervical cytology and its implication for screening policies. IARC Working Group on evaluation of cervical cancer screening programmes.

A collaborative study of screening programmes in eight countries was performed to estimate the risks of cervical cancer associated with different screening policies. Most of the data came from centrally organised screening programmes. Relative protection was higher in women who had had two or more negative results of screening tests than in those who had had only one negative smear, particularly in the first five years after the last test. There was little difference in the protection afforded by screening every year compared with every three years, but screening only once every five or 10 years offered appreciably less protection. The age of the women did not affect the sensitivity of the test or the sojourn time of the disease (the length of the detectable preclinical phase during which abnormal cytology could be picked up if a smear were taken); invasive cancer in women under 25 was rare. Centrally organised screening programmes were more effective than uncoordinated screening. Screening programmes should be aimed principally at women aged 35-60 but should start some years before the age of 35, and the intervals between screening should be three years or less.

Adult↗

Occurrence of second primary cancers among patients with cervical cancer in Osaka, Japan.

Using the data accumulated in the Osaka Cancer Registry, we conducted a study on the effect of radiotherapy for cervical cancer in causing second primary cancers. Two groups of patients with cervical cancer, 1,767 who were given radiotherapy and 1,377 who were not, were followed for 7-9 years on average. In the radiotherapy group, 79 women had second primaries, and in the nonradiotherapy group, 23 did. These figures were compared with the expected cancer incidence for all sites. In the radiotherapy group, a significantly high observed-to-expected ratio was noted in cancers of the rectum, lung, and bladder. The nonradiotherapy group showed no site with a significantly high observed-to-expected ratio. Factors causing the increased level of lung cancer were studied. Some evidence indicated the excess was probably not related to smoking but to radiation, although the mechanism is unknown.

Adult↗

Up-regulation of epidermal growth factor-receptors (EGF-R) by nicotine in cervical cancer cell lines: this effect may be mediated by EGF.

PROBLEM: Over-expression of epidermal growth factor-receptors (EGF-R) has been described in a variety of cancers, including cervical cancer. Nicotine may increase cellular proliferation rates through a mechanism involving EGF or EGF-R. In this study, we ascertain the effect of EGF antibodies on nicotine-enhanced proliferation rates in two cervical cancer cell lines. METHOD OF STUDY: We studied (a) nicotine-induced increase in the cellular expression of EGF-R in human papillomavirus (HPV)-positive ME-180 and HPV-negative HT-3 cervical cancer cell line cultures, using a semi-quantitative immunofluorescent antibody assay; (b) alterations in cellular proliferation in association with changes in EGF-R levels; and (c) the EGF-R mediation by EGF. RESULTS: Nicotine exposure at physiologically attainable plasma concentrations caused increased expression of EGF-R in both cervical cancer cell lines. Up-regulation of EGF-R was associated with increased cellular proliferation. Decreased expression of EGF-R was associated with decreased cellular proliferation. These data were consistent with EGF-R expression as a mechanism for the control of proliferation of the cervical cancer cells. The action of nicotine was abrogated when antibodies to EGF were added, implying that nicotine up-regulation of EGF-R may be mediated by EGF. CONCLUSIONS: Our data show that nicotine-induced proliferation of cervical cancer cells is mediated through EGF-R over-expression and that this action of nicotine utilizes EGF.

Cell Division↗

[Effect of 5'-DFUR used concurrently in radiotherapy and immunotherapy uterine cervical cancer--pilot study. Study of 5'-DFUR for Uterine Cervical Cancer].

We conducted a preliminary controlled study in order to evaluate 5'-DFUR dose dependency in efficacy and safety in combination therapy of radiotherapy, 5'-DFUR and SPG for patients with uterine cervical cancer, which was regarded as suitable for cases of radiotherapy. The patients were randomly allocated into group A (5'-DFUR 600 mg/body/day) and group B (5'-DFUR 800 mg/body/day), who underwent radiotherapy with simultaneous administration of 5'-DFUR and SPG (20 mg twice/week or 40 mg/ week). Those enrolled were 33 patients in stage II, III or IV a with histologically diagnosed primary squamous cell carcinoma of uterine cervix. CR was shown in 19, PR in 7, NC in 1, and PD in 2 out of 29 efficacy-evaluable cases, so the overall response rate was 89.7% (26/29, 95% CI 72.7%-97.8%). Regarding safety, some side effects were observed in 26 out of 33 safety-evaluable cases (81.3%, 95%, CI 63.6%-92.8%), but no serious cases. No significant difference in efficacy and safety was observed between the two treatment groups. These results suggested that the combination therapy of radiotherapy, 5'-DFUR and SPG might be one of the therapies whose effectiveness must be confirmed for advanced squamous cell carcinoma of uterine cervix. To confirm dose dependency of 5'-DFUR, it seems further consideration with more patients is needed.

Adjuvants, Immunologic↗

Primary care residents' characteristics and motives for providing differential medical treatment of cervical cancer screening.

BACKGROUND: Cervical cancer screening rates in the United States are sub-optimal. Physician factors likely contribute to these lower rates. Previous studies provide inconclusive evidence about the association between physician characteristics and the likelihood of addressing cervical cancer. This report assesses potential mechanisms that explain why certain providers do not address cervical cancer screening. METHODS: One hundred primary care residents from various specialties were asked to indicate the preventive topics they would address with a hypothetical white female in her early 20s, who was portrayed as living a "high risk" lifestyle, and visiting her provider only for acute care reasons. RESULTS: Among the provider characteristics assessed, only residents' ethnicity was associated with the likelihood of and time spent addressing cervical cancer screening. In particular, Asian-American residents were least likely to address cervical cancer, while African-American residents were most likely. A mediation analyses revealed that perceived barriers for addressing cervical cancer accounted for this difference. CONCLUSIONS: Study results suggest that there may be cultural factors among health care providers that may account for differential referral and treatment practices. Findings from this study may help identify factors that explain why cervical cancer screening rates are not higher.

Ethnicity↗

The prevalence of human papillomavirus type 16 and 18 DNA in cervical cancer in different age groups: a study on the incidental cases of cervical cancer in Norway in 1983.

In a study carried out to estimate the prevalence of genital Human Papilloma Virus (HPV) infection among cervical cancer patients in Norway, the following values were recorded using the southern blot hybridization method: 54.1% HPV 16, 9.5% HPV 18, 0% HPV 11, and 1.4% HPV 16 and 18 coinfection, yielding a total of 62.2% HPV positive cases in the study. An attempt to include a normal biopsy as "internal control" from each patient failed, as macroscopically normal tissue was often histologically abnormal. HPV infection did not relate to stage of disease, age, or 5-year survival, whereas the classic relationship between stage and survival was observed. A very high percentage of HPV positive cases occurred among older women, a fact which does not support the existence of a new HPV epidemic. The studied population is unique, as it represents 75 cases which comprise a representative sample of the 372 incidental cases of cervical cancer in Norway in 1983. To our knowledge this is the first study of its kind.

Adult↗

Cancer in husbands of cervical cancer patients.

We used the Swedish Family-Cancer Database to analyze the spectrum of cancers diagnosed in husbands of women with in situ or invasive cervical cancer, and we compared these to second carcinogenic events in women presenting with these cancers. Our hypothesis was increased cancer susceptibility from human papilloma virus (HPV). When the wives had in situ or invasive cervical cancer, the standard incidence ratios (SIRs) for anal cancer in husbands were 1.75 (95% CI = 1.05-2.62) and 1.92 (95% CI = 0.69-3.76). Anal cancer was also increased as a second primary cancer in women. Other common cancers were related to tobacco smoking. The results indicate that HPV infection is associated with anal cancer in both men and women.

Adult↗

Recent advances and problems in primary therapy for cervical cancer in Taiwan.

Cervical cancer is a serious health problem in Taiwan, with nearly 2700 women developing the disease each year. The estimated incidence of this disease from 1993 to 1997 was 21.8 per 100,000 woman-years. The lack of effective Papanicolaou smear screening systems was the major cause of the high prevalence rate before 1995. Surgery and radiotherapy are the standard treatments for early stage cervical cancer. For women with advanced stage cervical cancer, external-beam pelvic radiation followed by intracavitary radiotherapy is the treatment of choice. Although randomized clinical trials have shown that concurrent chemoradiotherapy should be regarded as the standard treatment for locally advanced cervical cancer (stage IIB to IVA), the impact of the complications associated with this treatment have not been evaluated in Taiwanese studies. Localized bulky (stage IB2 or bulky IIA) tumors are commonly treated with various combinations of chemotherapy, surgery and radiotherapy, despite unresolved concerns about the morbidity and effectiveness of this approach compared with definitive radiotherapy or radical surgery. Although about 60% of Taiwanese women with cervical cancer receive primary surgical treatment, about 20% do not receive treatment or receive non-standard therapies. Efforts are needed to increase the screening rate, to improve access to medical care, and to provide public education for patients to reduce the occurrence and mortality of cervical cancer in Taiwan.

Female↗

A case of invasive squamous cell carcinoma on the surface of pedunculated cervical leiomyoma presenting an exophytic cervical cancer.

BACKGROUND: Cervical cancer on the mucosal surface of a pedunculated cervical leiomyoma has not been reported. CASE: A 54-year-old woman who had a bulky protruding cervical tumor with a history of a vaginal bleeding was diagnosed as having squamous cell cancer of the cervix. She received a total of 45 Gy (1.8 Gy daily using 15MV photons) external pelvic irradiation. However, on the follow-up MRI, the mass showed no response. The pedunculated exophytic mass was excised and the pathologic examination showed a leiomyoma covered by cervical stroma and squamous cell carcinoma. She then received additional intracavitary brachytherapy. CONCLUSION: This is the first case reported in the literature of squamous cell carcinoma on the surface of peduculated cervical leiomyoma that presented as an exophytic cervical tumor.

Carcinoma, Squamous Cell↗

Second primary cancer following treatment for cervical cancer.

A follow-up study of 7535 women in Ontario was carried out to assess the occurrence of second primary cancers following the treatment of invasive carcinoma of the cervix between 1960 and 1975. The study was part of a larger international investigation of late radiation effects in patients with cervical cancer. Data were collected on the date and the type of treatment for cervical cancer and on the occurrence of second primary cancers diagnosed before 1980. Observed and expected numbers of second primary cancers, the latter determined according to Ontario incidence rates, were compared for individual sites and for all sites combined. There were significantly more primary cancers of the lung than expected (64 v. 15.52) but significantly fewer second primary cancers of the breast (56 v. 105.01) and colon (27 v. 43.31). Overall, there were significantly fewer (p less than 0.05) observed second primary cancers than expected (280 v. 394). Although the median follow-up period was less than 10 years there was no marked evidence of an excess of radiation-induced second primary cancers.

Carcinoma↗

Adenovirus-mediated transfer of a wild-type p53 gene and induction of apoptosis in cervical cancer.

In most cervical cancers, the function of p53 is down regulated. To explore the potential use of p53 in gene therapy for cervical cancer, we introduced wild-type p53 into cervical cancer cell lines via a recombinant adenoviral vector, Ad5CMV-p53, and analyzed its effects on cell and tumor growth. The transduction efficiencies of all cell lines were 100% at a multiplicity of infection of 100 or greater. The p53 protein was detected in Ad5CMV-p53-infected cells. Protein expression peaked at day 3 after infection and lasted 15 days. The Ad5CMV-p53-infected cells underwent apoptosis, and cell growth was greatly suppressed. The Ad5CMV-p53 treatment significantly reduced the volumes of established s.c. tumors in vivo. These results indicate that transfection of cervical cancer cells with the wild-type p53 gene via Ad5CMV-p53 is a potential novel approach to the therapy of cervical cancer.

Adenoviridae↗