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PubMed2005

Management of recurrent cervical cancer.

Treatment for cervical cancer is very successful, especially in early stages. However, most patients presenting in late stages of disease will experience recurrence. The prognosis of recurrent disease is very poor and treatment options are limited. The diagnosis of recurrence may be apparent or difficult, but determining the extent of disease is always complex. Routine follow-up of asymptomatic patients has other objectives and is not a reliable way to detect recurrences. Symptomatic patients require extensive investigation to detect the extent of the disease. For patients with central pelvic recurrences, exenteration offers the prospect of survival in more than one-third of cases. Newer developments include laterally extended endopelvic resection that may become an option for patients with more extensive pelvic recurrence. For patients with recurrences of cervical cancer, the roles of second-time radiotherapy or postradiation chemotherapy are very limited. Palliative treatment is important for all patients with untreatable disease. Pain relief forms a central part of palliative care. Caregivers also experience emotional feelings and probably function best in a system offering strong colleageal support.

Female↗
PubMed2003

Phase I study of combined radiation, hyperthermia and intra-arterial carboplatin for local recurrence of cervical cancer.

BACKGROUND: Patients with cervical cancer who develop pelvic recurrence after primary surgery are usually treated with radiation-based therapy. However, their prognoses are dismal. We conducted a phase I study of combined radiation, hyperthermia and intra-arterial (IA) carboplatin for local recurrence of cervical cancer. PATIENTS AND METHODS: Patients with local recurrence of cervical cancer without extrapelvic recurrence were included in this study. Carboplatin was given as a 5-min IA infusion without hydration just before pelvic radiation every day. External pelvic irradiation (1.8 Gy/day for 28 days) was performed according to local standard schedules. After 20 Gy had been administered, hyperthermia was performed once a week with a radio frequency heating system for four cycles. RESULTS: Fifteen patients were entered through the four dose levels of carboplatin. The maximum tolerated dose was determined to be 25 mg/m(2 )and the dose-limiting toxicities were leukocytopenia, neutrocytopenia and diarrhea. Grade 3/4 leukocytopenia and diarrhea were observed in nine (60%) and three (20%) of 15 patients. Tumor responses included five complete responses and nine partial responses, and the overall response rate was 93.3% (14 of 15) (95% confidence interval 59.4% to 100%). Tumor reductions were observed only at 20 Gy in 10 cases of 14 responders (71.4%). CONCLUSION: The combination therapy of radiation, hyperthermia and IA carboplatin is safe and well-tolerated for locally recurrent cervical cancer.

Adult↗
PubMed2005

Pre-exenterative chemotherapy, a novel therapeutic approach for patients with persistent or recurrent cervical cancer.

BACKGROUND: Most cervical cancer patients with pelvic recurrent or persistent disease are not candidates for exenteration, therefore, they only receive palliative chemotherapy. Here we report the results of a novel treatment modality for these patients pre-exenterative chemotherapy- under the rational that the shrinking of the pelvic tumor would allow its resection. METHODS: Patients with recurrent or persistent disease and no evidence of systemic disease, considered not be candidates for pelvic exenteration because of the extent of pelvic tumor, received 3-courses of platinum-based chemotherapy. Response was evaluated by CT scan and bimanual pelvic examination; however the decision to perform exenteration relied on the physical findings. Toxicity to chemotherapy was evaluated with standard criteria. Survival was analyzed with the Kaplan-Meier method. RESULTS: Seventeen patients were studied. The median number of chemotherapy courses was 4. There were 9 patients who responded to chemotherapy, evaluated by bimanual examination and underwent pelvic exenteration. Four of them had pathological complete response. Eight patients did not respond and were not subjected to surgery. One patient died due to exenteration complications. At a median follow-up of 11 months, the median survival for the whole group was 11 months, 3 months in the non-operated and 32 months in those subjected to exenteration. CONCLUSION: Pre-exenterative chemotherapy is an alternative for cervical cancer patients that are no candidates for exenteration because of the extent of the pelvic disease. Its place in the management of recurrent disease needs to be investigated in randomized studies, however, its value for offering long-term survival in some of these patients with no other option than palliative care must be stressed.

Adult↗
PubMed2002

Postmodern cancer: the role of human immunodeficiency virus in uterine cervical cancer.

The association between cervical cancer and human papillomavirus (HPV) is well known, but its association with human immunodeficiency virus (HIV) is controversial. Coinfection with HPV and HIV is to be expected and recent epidemiological data from Africa show that cervical cancer is the most common AIDS defining neoplasm in women. Unlike other AIDS defining neoplasms, the occurrence of cervical cancer is not dependent on immune compromise. HIV alters the natural history of HPV infection, with decreased regression rates and more rapid progression to high grade and invasive lesions, which are refractory to treatment, requiring more stringent intervention and monitoring. The more aggressive behaviour is mirrored by a different molecular pathway. HIV associated cervical cancers are thought to progress through the microsatellite instability pathway, whereas HIV negative ones progress through loss of heterozygosity. Interaction is probably via viral proteins, with HIV proteins enhancing effectiveness of HPV proteins, and perhaps contributing to cell cycle disruption. Dysregulation of the cellular and humoral arms of the local and systemic immune systems may ensure disease progression. Furthermore, HPV infection may predispose to HIV infection and facilitate its progression.

Female↗
PubMed2005

The role of viral integration in the development of cervical cancer.

The development of invasive cervical cancer is associated with human papillomavirus (HPV) infection and subsequent integration into the host epithelium. More than 99% of cervical cancers contain HPV sequences, and many of these contain a truncated HPV genome integrated into a single position within the host genome. Studies examining the role of viral integration in cervical cancer development have found that the sites of integration appear randomly distributed throughout the genome. This, and the observation that it frequently takes years after HPV infection for cervical cancer to develop, has led to the current paradigm that the site of HPV integrations is unimportant to the invasive cervical cancer that eventually develops. In our previous studies of HPV16 and HPV18 integration in cervical cancers, we also found integrations throughout the genome, but observed as well that more than half of the integrations occurred within common fragile site regions. To determine if HPV integration might play an important role in cervical cancer, we conducted two complementary studies. We first localized 40 new HPV16 integration sites from cervical tumors from women in Hong Kong; this, together with previous integration studies, provided a better picture of the distribution of integration sites throughout the genome. We then analyzed the sites of viral integration in an in vitro model of HPV integration. By comparing the sites of HPV integration in vivo (in multiple primary cervical tumors) to those obtained in vitro, the data can help to determine if HPV integrations observed in vivo are the result of random and nonselected integrations.

Base Sequence↗
PubMed1992

The epidemiology of cervical cancer and its precursors.

Cervical cancer is considered to be a preventable disease because of its lengthy preinvasive state, the effectiveness of screening programs, and the availability of effective treatment options for preinvasive lesions. Thus, identifying women with a greater probability of developing the disease is important to promoting early detection and instituting prompt treatment. Questions concerning risk factors that influence a woman's chances of developing cervical cancer are being addressed through research. Nurses who understand the epidemiology of cervical cancer and who are skilled in taking comprehensive health histories can play a major role in early detection and prompt treatment of cervical cancer by educating all women, including sexually active teenagers, about obtaining regular gynecologic screening exams.

Clinical Protocols↗
PubMed2001

Cervical cancer in Latin America.

Cervical cancer is a common cause of morbidity and mortality in developing countries. In Latin America, the incidence rates in several cities are among the highest worldwide, probably due to a high frequency of risk factors and/or a low screening coverage for cervical cancer. Epidemiologic studies conducted in Latin America (and some in the Caribbean), that have investigated the main risk factors for the disease, as well as screening coverage by Papanicolaou (Pap) smear, were reviewed. The prevalence of human papillomavirus (HPV) infection among women with negative Pap smears does not seem to explain the risk observed in Latin American countries. Results of some studies have suggested that reproductive factors and male sexual behavior might be responsible, at least partially, for the high occurrence of cervical cancer in Latin America. Concerning cytology screening, many women have a smear taken regularly (some every year). However, a significant proportion of women, probably those with a high risk of cancer of the cervix, have never had a Pap test. To reduce cervical cancer in these countries, screening programs in Latin America should have a wider coverage, especially reaching those women at higher risk. Semin Oncol 28:188-197.

Developing Countries↗
PubMed2000

Management of stage I cervical cancer in pregnancy.

UNLABELLED: Although cervical carcinoma is the most common gynecologic malignancy associated with pregnancy, its occurrence is rare with an incidence of approximately 1 per 1,200 to 10,000 pregnancies. There are inadequate data addressing both the obstetric implications of the diagnostic evaluation and the impact of intervention on maternal and infant outcomes. Certain conclusions and recommendations, however, can be drawn from the available data. Diagnostic evaluation includes cytological screening, colposcopy and if necessary, biopsy, and selective conization. Staging of the pregnant patient is modified to minimize radiation exposure to the developing fetus. The treatment schema for patients with stage I cervical cancer in pregnancy varies with the stage of disease and gestational age at diagnosis. With close surveillance, deliberate delay of therapy to achieve fetal maturity is a reasonable option for patients with microinvasive and early stage IB cervical cancer. Tumor characteristics and maternal survival are not adversely affected by pregnancy. Conversely, cervical cancer does not seem adversely to affect pregnancy. However, timing and type of therapy may have a significant influence on the fate of the fetus. In counseling patients with cervical cancer during pregnancy, many factors must be considered, including the patient's desire for the pregnancy, stage of disease, and gestational age at diagnosis. Pregnant patients with stage I cervical cancer should be fully informed of all possible treatment options and consequences. The care of these patients should be closely coordinated by experts in perinatology and gynecologic oncology. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the signs and symptoms of cervical cancer during pregnancy and the indications for conization during pregnancy, as well as being able to outline management strategies for the various stages of cervical cancer during pregnancy.

Adult↗
PubMed2006

Radiosensitizers in cervical cancer. Cisplatin and beyond.

Cervical cancer continues to be a significant health burden worldwide. Globally, the majority of cancers are locally advanced at diagnosis; hence, radiation remains the most frequently used therapeutical modality. Currently, the value of adding cisplatin or cisplatin-based chemotherapy to radiation for treatment of locally advanced cervical cancer is strongly supported by randomized studies and meta-analyses. Nevertheless, despite these significant achievements, therapeutic results are far from optimal; thus, novel therapies need to be assayed. A strategy currently being investigated is the use of newer radiosensitizers alone or in combination with platinum compounds. In the present work, we present preclinical information on known and newer cytotoxic agents as radiosensitizers on cervical cancer models, as well as the clinical information emanating from early phase trials that incorporate them to the cervical cancer management. In addition, we present the perspectives on the combined approach of radiation therapy and molecular target-based drugs with proven radiosensitizing capacity.

Journal Article↗
PubMed2006

The health-care practices of Vietnamese-Canadian women: cultural influences on breast and cervical cancer screening.

Breast and cervical cancer are major contributors to morbidity and mortality among Vietnamese-Canadian women. Vietnamese women are at risk due to their low participation rate in screening programs for these cancers. The purpose of this exploratory qualitative study, informed by Kleinman's Exploratory Model of Health and Illness, was to explore the participation of Vietnamese-Canadian women in screening for breast and cervical cancer; the appropriateness of current cancer-prevention services for Vietnamese women; and the influence of social, cultural, political, historical, and economic factors, shaped by race, gender, and class, on the screening practices of Vietnamese-Canadian women. Fifteen Vietnamese-Canadian women and 6 health-care providers were interviewed. Analysis revealed that several factors influenced the women's participation in cancer screening. This paper reports on the process by which cultural knowledge and beliefs contributed to the women's health-care practices. The study revealed that the following cultural factors influenced the women's level of participation in screening programs for breast and cervical cancer: cultural knowledge and values with regard to women's bodies, conceptualization of health and illness, and beliefs and values concerning the patient/health-care provider relationship. The author offers recommendations on the promotion of screening for breast and cervical cancer among Vietnamese-Canadian women.

Aged↗
PubMed2004

Health care disparities and cervical cancer.

OBJECTIVES: We compared cervical cancer incidence, stage at diagnosis, and survival in Medicaid-insured and non-Medicaid-insured populations. METHODS: We stratified the sample by age and used ordered logistic regression to predict stage at diagnosis and used Cox proportional hazards regression to predict survival. RESULTS: Medicaid insured nearly one quarter of women diagnosed with cervical cancer. The likelihood of late-stage disease was greatest for women who enrolled in Medicaid after diagnosis. Women younger than 65 years who enrolled in Medicaid after diagnosis were more likely to die from cervical cancer than were women who were not insured by Medicaid (hazard ratio=2.40, 95% confidence interval=1.49, 3.86). CONCLUSIONS: Our study underscores the importance of cervical cancer screening programs targeted at low-income women.

Adult↗
PubMed2004

Evaluation of a selectively oncolytic adenovirus for local and systemic treatment of cervical cancer.

Treatment options for disseminated cervical cancer remain inadequate. Here, we investigated a strategy featuring Ad5-Delta 24 RGD, an oncolytic adenovirus replication-competent selectively in cells defective in the Rb-p16 pathway, such as most cervical cancer cells. The viral fiber contains an alpha(v)beta(3) and alpha(v)beta(5) integrin-binding RGD-4C motif, allowing coxsackie-adenovirus receptor-independent infection. These integrins have been reported to be frequently upregulated in cervical cancer. Oncolysis of cervical cancer cells was similar to a wild-type control in vitro. In an animal model of cervical cancer, the therapeutic efficacy of Ad5-Delta 24 RGD could be demonstrated for both intratumoral and intravenous application routes. Biodistribution was determined following intravenous administration to mice. Further preclinical safety data were obtained by demonstrating lack of replication of the agent in human peripheral blood mononuclear cells. These results suggest that Ad5-Delta 24 RGD could be useful for local or systemic treatment of cervical cancer in patients with disease resistant to currently available modalities.

Adenoviridae↗
PubMed2003

Immunohistochemical and quantitative competitive PCR analyses of midkine and pleiotrophin expression in cervical cancer.

OBJECTIVE: The aim of this study was to determine midkine (MK) and pleiotrophin (PTN) expression in cervical cancer. METHODS: Prospective study in tertiary teaching hospital. Normal and cancerous cervical tissues were obtained from healthy women (n = 19) and from patients with cervical cancer (n = 42). The expressions of MK and PTN mRNA and protein were examined by quantitative competitive PCR and by immunohistochemistry. MK and PTN mRNA and protein expressions were examined with respect to tumor stage and size. RESULTS: The expressions of midkine and pleiotrophin mRNA in cervical cancer were higher than those in the normal cervix (MK, 175.59 +/- 63.3 vs 1.00 +/- 0.18 fmol, respectively; PTN, 3.18 +/- 1.25 vs. 0.86 +/- 0.12 fmol, respectively, P < 0.05), and their expressions were not correlated with cervical cancer stage or size of the tumor. The expressions of MK and PTN protein in cancerous tissue were higher than those in the normal cervix (P < 0.05). Moreover, the protein expression of MK, but not of PTN, correlated with tumor stage and size. The expressions of MK and PTN were not correlated with vascular density. CONCLUSIONS: Our results suggest that increased midkine mRNA and protein expressions are associated with the carcinogenesis of cervical cancer.

Carrier Proteins↗
PubMed2005

Costs of colposcopy services and their impact on the incidence and mortality rate of cervical cancer in Canada.

OBJECTIVE: Organized cervical cancer screening services consisting of conventional Papanicolaou cervical smears, colposcopy, and related treatment modalities are readily available in all provinces. The purpose of this report was to study the impact of colposcopy usage and costs on cervical cancer incidence and mortality rates in several Canadian provinces. Knowledge of such information is essential before newer technology such as liquid-based cytology and human papillomavirus testing is introduced or replaces the traditional systems used. MATERIALS AND METHODS: The Ministries of Health of five provinces were contacted and asked to furnish information on the number of colposcopic services and fee-for-service costs for these and for cryosurgery, carbon dioxide laser vaporization, loop electrosurgical excisions, and cold-knife conizations for the year 2000. Canadian Cancer Society estimates of incidence and mortality rates for cervical cancer were also obtained. RESULTS: All provinces had similar incidence and mortality rates for cervical cancer; however, the number of colposcopic services on a per-capita basis varied substantially, with Manitoba and Ontario having rates that were approximately two or three times higher. Fee-for-service payments for colposcopy were similar in the Provinces studied but unit costs for surgical treatment services were highest in Ontario and British Columbia. CONCLUSIONS: Although both the incidence and mortality rates for cervical cancer in Canada fell dramatically after the Walton Report in 1976, these rates have plateaued over the past decade despite widespread availability of colposcopy and related ambulatory treatment services. Higher rates of colposcopy usage do not seem to result in lower incidence rates for this disease. Unit costs for colposcopy are similar among the provinces reviewed, but substantial difference exists for certain treatment services. Additional studies are recommended before the widespread introduction or replacement of existing methods with newer, more costly techniques.

Canada↗
PubMed2003

Effect of bitter melon (Momordica charantia Linn) on level and function of natural killer cells in cervical cancer patients with radiotherapy.

Cervical cancer patients have a defective immune system. There is a decrease of total white blood cell count including lymphocytes and natural killer (NK) cells. NK cells, one type of lymphocytes, play a role to eliminate cancer cells by antibody dependent cell mediated cytotoxicity (ADCC) mechanism. Previous studies have shown that P-glycoprotein (170 kDa, transmembrane protein) may be a transporter for cytokine releasing in ADCC mechanism. This study proposed to explore the role of bitter melon intake in cervical cancer patients undergoing normal treatment (radiotherapy). Subjects were divided into three groups: 1) normal control (women 35-55 years, n = 35), 2) patient control (n = 30) and 3) patient treatment (n = 30) groups. Patient control and patient treatment groups were cervical cancer patients (stage II or III) treated with radiotherapy (without or with bitter melon ingestion). Blood samples of patient control and patient treatment groups were analyzed for NK cells percentage and P-glycoprotein level. Bitter melon is a Thai herb. Previous studies have shown that bitter melon can stimulate lymphocyte activity in vitro and in vivo (mouse). The authors hope that bitter melon could stimulate the increase of NK cells percentage and P-glycoprotein level on the membrane in blood samples from cervical cancer patients who ingest bitter melon. The results showed an increased percentage of NK cells in patient control and patient treatment groups. The increase in each group is significant (p < 0.05) when compared with the percentage of NK cells from second and third blood sampling time (after radiation with of without bitter melon intake for 45 and 90 days) with first blood sampling time (before treatment). The results also show a significant decrease of P-glycoprotein level (p < 0.05) in second and third blood sampling times when compared with first blood sampling time of the patient treatment group. There was no significant difference of P-glycoprotein (P-gp) level from first, second and third blood sampling times in patient control group. Bitter melon ingestion did not affect NK cell level but it affected the decrease of P-gp level on NK cell membrane.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Human secreted frizzled-related protein is down-regulated and induces apoptosis in human cervical cancer.

To identify genes involved in cervical carcinogenesis, the mRNA differential display method was used. A 220-bp cDNA fragment called CA11 was present in normal cervical tissue but not in primary cervical cancer tissue or cervical cancer cell lines. CA11 exhibited 98% homology with the recorded human secreted frizzled-related protein (hsFRP) sequence. A dominant hsFRP mRNA transcript of approximately 4.6 kb was present in three normal cervical tissues examined. Expression of the transcript was nearly absent from three cervical cancer tissues and from five human cervical cancer-derived cell lines. Results from in situ hybridization showed that the hsFRP transcript was confined to the normal cervical epithelial layer. When hsFRP-transfected HeLa and CUMC-6 cervical cancer cells were cultured in serum-free medium, most of the cells died within 8 days. This effect is associated with the apoptotic process. The caspase-3 inhibitor 1, Ac-DEVD-CHO, blocked hsFRP-induced apoptotic cell death. Additionally, cleavage of poly (ADP-ribose) polymerase in hsFRP-transfected cells was confirmed by colorimetric assay. These results indicate that the hsFRP gene probably functions as a tumor suppressor in normal cervical epithelium and down-regulation of hsFRP contributes to development of cervical cancer.

Animals↗