[The cancer patient - illustrated by cervical cancer].
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Female↗
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Management of cervical cancer.
AIMS: The aim of the article was to review the current approach to management of cervical cancer. METHODS: The relevant literature has served as a source for review of different options applied in the management of cervical cancer. RESULTS: Treatment of invasive cervical cancer is affected by the stage of the disease, which is based on clinical evaluation. Microinvasive carcinoma of the cervix has limited metastatic potential and therefore is most likely curable by non-radical treatment. There is no standard management of stage Ib-IIa cervical carcinoma. Both radical surgery and radical radiotherapy have proven to be equally effective, but differ in associated morbidity and complications. Most often, stage Ib1 cervical cancer is treated by radical hysterectomy with pelvic lymphadenectomy. Laparoscopically assisted radical vaginal hysterectomy has shown similar efficacy and recurrence rates. Radical vaginal trachelectomy with laparoscopic pelvic lymphadenectomy may be an option in small cervical cancer where preservation of fertility is desired. There is lot of conflicting published work regarding the treatment of bulky stage Ib-IIa cervical cancer. While some centers are performing primary surgery as for Ib1 disease followed by tailored postoperative radiation with or without chemotherapy, the others are in favor of primary chemo-radiation therapy. Neoadjuvant chemotherapy followed by radical surgery has emerged as a possible alternative, which may improve a survival in patients with stage Ib2 disease. Concomitant chemoradiation is becoming a new standard in treatment of advanced disease, because it has been clearly shown to improve disease-free, progression-free and overall survival. Management of recurrent disease depends on previous treatment, site and extent of recurrence, disease-free interval and patient's performance status. CONCLUSIONS: Treatment decisions should be individualized and based on multiple factors including the stage of the disease, age, medical condition of the patient, tumor-related factors and treatment preferences, to yield the best cure with minimum complications.
Antineoplastic Agents↗
Therapeutic potential of an adenovirus expressing p73 beta, a p53 homologue, against human papilloma virus positive cervical cancer in vitro and in vivo.
Human papilloma virus (HPV) infection is the most important risk factor for cervical cancer development. p53 based gene therapy is not suitable for cervical cancer because HPV oncoprotein E6 inactivates p53 protein by targeting it for ubiquitin mediated degradation. Here we evaluated the efficiency of Ad-p73, a replication deficient adenovirus expressing p73beta a p53 homologue, to inhibit the growth of HPV positive cervical cancer cells in vitro using tissue culture system and in vivo using human xenografts in nude mice. Ad-p73, but not Ad-p53 (p53 adenovirus), inhibited the growth in vitro of three different HPV positive cervical cancer cell lines, HeLa, ME180, and SiHa, efficiently, which correlated with stable expression of functional p73 protein. However, the growth of a HPV negative cervical cancer cell line, C33A, was inhibited equally by both Ad-p73 and Ad-p53. In addition, we show that Ad-p73 preinfected HeLa cells and HCT116 E6 cells, an E6 stable cell line, failed to form tumors in nude mice unlike Ad-p53 or Ad-LacZ preinfected cells. Moreover, Ad-p73, but not Ad-p53, inhibited completely the growth of already established tumors of HeLa or HCT116 E6 cells. Furthermore, the ability of p73 to inhibit the growth of these tumors correlated with the stable expression of p73 protein with the concomitant induction of its target gene p21(WAF1/CIP1) and induction of apoptosis in tumor cells. These results suggest that Ad-p73 inhibits efficiently the growth in vitro and tumorigenicity and tumor growth in vivo of HPV positive cervical cancer cells and that p73-based approach should be explored as a potential therapeutic model for the treatment of cervical cancer.
Adenoviridae↗
Invasive cervical cancer in the 1990s.
The death rate from invasive cervical cancer has decreased by 70% since the classic work by Papanicolaou and Traut in 1941 on the use of cytologic evaluation to detect cancer of the uterine cervix in the preinvasive in situ stage--a nearly 100% curable disease. Unfortunately, the survival stage for stage of invasive cervical cancer has remained static over the nearly 5 decades since their report. However, discoveries in the decade of the 1970s of the natural spread of cervical cancer, not only to the known pelvic lymph nodes, but the increasing incidence of paraaortic lymph node metastasis with advanced stages, the higher dose of radiation required to sterilize pelvic lymph node metastasis discovered at the time of radical hysterectomy or for locally advanced cervical cancer treated solely by radiation therapy, and the use of radiation potentiators, such as hydroxyurea, should lead to the significant reduction in the annual 7,000 deaths from this disease in the decade of the 1990s.
Female↗
Coexpression of Notch1 and NF-kappaB signaling pathway components in human cervical cancer progression.
OBJECTIVES: Features of deregulated Notch1 signaling and NF-kappaB activation have independently been reported in cervical cancers. Here, we have extended these observations and examined both these pathways simultaneously in human cervical cancer tissue. Further, we have investigated the potential cross-talk between these pathways in a human cervical cancer derived cell line CaSki, which mirrors features of Notch activation as in the majority of human cervical cancers. METHODS: Cervical tissue samples were analyzed for the expression of Notch1, Jagged 1, Hes1, pAKT, NF-kappaB p50, NF-kappaB p65, IkappaB-alpha, Bcl-2, CyclinD1, Cdk9, c-Fos, and p53 by immunohistochemistry. A total of 352 samples were analyzed which included 69 normal cervical tissue, 132 preinvasive lesions and 151 squamous cell carcinomas of the uterine cervix. Dual immunofluorescent analysis was performed to evaluate the coexpression of Notch1 and NF-kappaB. Transcriptional reporter assays and xenografts were undertaken with CaSki cells. RESULTS: Features of Notch1 activation as measured by intracellular Notch1, high levels of Jagged1, Hes1 and Cdk9 were paralleled by nuclear translocation of both NF-kappaB p50 and p65 with target gene expression (IkappaB-alpha, Bcl-2, and CyclinD1) in human cervical cancer sections. Reporter assays in CaSki cells are consistent with Notch being an upstream regulator of NF-kappaB. Further, the xenografts recreate key aspects of human cancer tissue. CONCLUSIONS: Results from this study suggest that there is a co-activation of Notch1 and NF-kappaB signaling pathways at the cellular level in the majority of human cervical cancers, with Notch as an upstream regulator.
Animals↗
Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression.
The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Umeå University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors.
Adult↗
[Recent trend in the treatment of uterine cancer--surgical treatment of cervical cancer].
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Female↗
[Analysis of risk factors for cervical cancer in Xiangyuan County, Shanxi Province].
OBJECTIVES: To investigate the risk factors for cervical cancer in the areas of high incidence, and provide evidence for current intervention of cervical cancer. METHODS: In the areas of Xiangyuan County, Shanxi Provicne with high incidence of cervical cancer, 1 997 women were interviewed using a questionnaire, including baseline information, menstrual, marital and pregnancy histories, sexual behavior, health habits, contraception, medical history and family history of cancer, etc., after its screening with six kinds of methods. All subjects, including 84 cases with pathological diagnosis of greater than cINI, and 1 784 cases with pathological diagnosis of normal, were tested for high-risk HPV. RESULTS: The overall rates of HPV infection were 20.8% (415/1 997) in high-risk subjects, 97.7% and 14.2% in the cases and control groups, respectively. Univariate analysis showed that risk factors with statistical significance included high-risk HPV infection, age at first sexual intercourse, history of pregnancy and abortion, the number of sexual partners and family history of cancer. Analysis with non-conditional logistic regression model revealed high-risk HPV infection, multiple sexual partners and family history of cancer associated obviously with occurrence of cervical cancer. In addition, there was significantly positive relationship between HPV infection, which increased with the number of sexual partners, and extramarital sexual activity both in males or females. CONCLUSIONS: The main risk factor for cervical cancer in this region was high-risk HPV infection, which related to sexual behavior, hygienic habits during menstruation and puerperium. It was particularly important to detect and treat precancerous lesions and to implement behavior modification. In addition, further research on genetic susceptibility was suggested.
Abortion, Induced↗
Risk of cervical cancer following negative smears in Maribo County, Denmark, 1966-1982.
In order to estimate the risk of developing cervical cancer among women who had originally had cytologically normal smears, information has been collected on all smears taken in Maribo County, Denmark, in the years 1966-1982, among women born between 1918 and 1952. A total of 27,811 women are included in the study, and cases of invasive cervical cancer developing in the study population have been identified from the local department of pathology and from the National Cancer Registry. The incidence of cervical cancer has been tabulated by number of previous negative smears and by time elapsed since last negative smear. Women with one previous negative smear have a zero risk of developing cervical cancer during the first year following the negative smear. The incidence among these women increases with length of time since the negative smear and reaches the same level as that of unscreened women during the fifth year of follow-up. Women with two to four previous negative smears also have a negligible risk of developing cervical cancer during the first two years following the last negative smear. The incidence among these women increases less over time than the incidence for women with one previous negative smear. No case of cervical cancer was observed among 7716 women with five or more previous negative smears. The study indicates that the five-year risk of developing cervical cancer is 48% lower in women with one previous negative smear than in an unselected population of unscreened women. The five-year risk for women with two previous negative smears is 62% lower than that for unscreened women.
Adolescent↗
[Analysis on incidence for cervical cancer in Qidong during 1972 - 2000].
OBJECTIVE: To investigate the trends of incidence for cervical cancer in the years of 1973 - 2000, in Qidong, a city in south China, with a population of 1.16 M. METHODS: Crude incidence rate of cervical cancer was calculated by using incident case data from Qidong Cancer Registry, which was founded in 1972, and age-standardized rates were computed according to China age structure of 1964 (CASR), and world age structure of 1960 (WASR). The epidemiological features and secular change trends of the cancer were described. RESULTS: Six hundred and thirty-one new cases of cervical cancer were reported in Qidong during the years of 1973 to 2000, ranking the eighth and accounting for 3.25% among all sites of cancers in women. The crude annual incidence rate during the period was 3.96 per 100,000 on average, China age-standardized rate (CASR) was 2.67 per 100,000, and world age-standardized rate (WASR), 3.66 per 100,000. The incidence of cervical cancer was 2.97 per 100,000 for the last 14 years, and 5.01 per 100,000 for the first 14 years, showing a decreasing trend (P < 0.01). Age-specific rates showed that the incidents among those aged over 55 in the recent 14 years were markedly lower than that in the first 14 year period (P < 0.01). CONCLUSIONS: Qidong is a relatively low incidence area of cervical cancer, with a decreasing trend among aged women, according to population-based cancer registration data. This incidence data on cervical cancer could be used as a base for strategic treatment and prevention of the disease.
Adult↗
Cervical cancer screening among Cambodian-American women.
Southeast Asian women have higher invasive cervical cancer incidence rates and lower Pap testing frequencies than most other racial/ethnic groups in the United States. However, there is little information about the cervical cancer screening behavior of Cambodian-American women. Cambodian residents of Seattle were surveyed in person during late 1997 and early 1998. The PRECEDE model was used to guide the development of items that assessed predisposing, reinforcing, and enabling factors associated with cervical cancer screening participation. The estimated overall survey response was 72%. Four hundred thirteen women completed our questionnaire. Approximately one-quarter (24%) of the respondents had never had a Pap test, and over one-half (53%) had not been screened recently. The following variables were positively associated with a history of at least one Pap smear: younger age, greater number of years since immigration, belief about Pap testing for postmenopausal women, prenatal care in the United States, and physician recommendation. Women who believed in karma were less likely to have ever been screened for cervical cancer than those who did not. Six variables independently predicted recent screening: age; beliefs about regular checkups, cervical cancer screening for sexually inactive women, and the prolongation of life; having a female doctor; and a previous physician recommendation for Pap testing. The study findings indicate that culturally specific approaches might be effective in modifying the cervical cancer screening behavior of immigrant women. Programs targeting Cambodian-Americans are likely to be more effective if they are multifaceted and simultaneously address predisposing, reinforcing, and enabling factors.
Adolescent↗
Reproductive variables and risk of uterine cervical cancer in Norwegian registry data.
The influence of reproductive variables on cervical cancer incidence, controlling for other sociodemographic factors, was estimated in Norwegian register and census data, using Poisson regression models. Among the 1.3 million women under observation, a total of 2,870 cases of cervical cancer were diagnosed. According to models restricted to parous women, parity level had no independent impact on cervical cancer incidence, but a clear effect of age at first birth was noted. It was most pronounced in the squamous cell carcinomas, where the incidence was reduced by 48 percent from age at first birth < 21 years to age at first birth 27+ years. Women without children had the same cervical cancer incidence as parous women with a first birth after age 24. The sociodemographic variables controlled for exerted a strong net effect on the cervical cancer incidence. Educational level was related inversely to the cancer risk. Moreover, an increased risk was seen for women who had given birth when they were still single (never married) and for those who were divorced/separated at the time of the last previous census. A fairly small excess risk was found to be associated with living in non-rural compared with rural areas.
Adult↗
Cervical cancer screening: are the 1989 recommendations still valid? National Workshop on Screening for Cancer of the Cervix.
Although screening for cervical cancer has been shown to be effective in reducing the morbidity and mortality associated with this disease, and despite many attempts to encourage the development of provincial programs, as of 1995 no province had a comprehensive screening program for cervical cancer. Participants at the Interchange '95 workshop, held in Ottawa in November 1995, reviewed the recommendations of the 1989 National Workshop on Screening for Cancer of the Cervix and identified factors that have impeded their implementation. Participants discussed the need for comprehensive information systems, quality control and strategies to increase recruitment of unscreened and underscreened women. They concluded that the formation of a Cervical Cancer Prevention Network involving key stakeholders will facilitate the development and implementation of provincial programs to ensure optimal screening. They agreed that, in the interim, recommendations for practising physicians should remain as they were following the 1989 workshop.
Canada↗
[Neoadjuvant chemotherapy for advanced cervical cancer].
Twenty-five patients with advanced cervical cancer (IIb-IVa) were treated with neoadjuvant chemotherapy followed by radical hysterectomy or radiotherapy. According to the evaluation by MRI, complete response was achieved in 2 cases and partial response in 17 cases. Eventually the response rate was 76%. The response rate was higher in squamous cell carcinomas (85%) than adenocarcinomas or adenosquamous carcinomas (67%). The histological effect is superior in squamous cell carcinomas than adenocarcinomas or adenosquamous carcinomas. Radical hysterectomy was performed in 5 cases of 11 (45%) stage III-IVa cervical cancers. There was no correlation between tumor size and response to NAC. NAC therapy may be useful therapy in advanced cervical cancers, especially squamous cell carcinomas.
Adenocarcinoma↗
Current controversies in high-dose-rate versus low-dose-rate brachytherapy for cervical cancer.
The use of brachytherapy in the treatment of cervical cancer has increased worldwide since its initial introduction over 100 years ago. However, certain aspects of the use of high-dose-rate (HDR) versus low-dose-rate (LDR) brachytherapy continue to be controversial, particularly the role of HDR in FIGO Stage III cervical cancer and the use of HDR with concurrent chemotherapy. This study represents a systematic literature review of prospective and retrospective series of patients with cervical carcinoma treated with external-beam radiation (EBRT) followed by either HDR or LDR radiation. The local control rates, survival rates, and treatment-related complications in patients with Stage III cervical cancer treated with HDR or LDR and those treated with concomitant chemotherapy are examined. Patients with Stage III cervical cancer treated with EBRT and brachytherapy have a local control rate of >50% in most series. Randomized prospective and retrospective studies show overall statistically equivalent local control, overall survival, and complication rates between HDR and LDR. However, LDR may be preferable for large, bulky tumors at the time of brachytherapy. Retrospective studies of HDR and concurrent chemotherapy are limited but have demonstrated toxicity rates similar to those with LDR. Selected patients with Stage III cervical carcinoma who have an adequate response to EBRT and concomitant chemotherapy may be treated with HDR brachytherapy. The existing literature shows no significant increase in complications in patients treated with HDR and concurrent chemotherapy; however, sufficient tumor shrinkage prior to HDR and careful monitoring of the dose to the normal tissues are imperative.
Brachytherapy↗
Hispanic women's perceptions regarding cervical cancer screening.
OBJECTIVE: To examine factors affecting cervical cancer screening behaviors. DESIGN: Qualitative, descriptive. SETTING: Interviews were conducted in participants' homes. PARTICIPANTS: Purposive sample of 20 Hispanic women 18 to 65 years of age. RESULTS: Participants accessed the health care system primarily during times of illness or in association with impending marriage, obtaining birth control, or childbearing. Barriers to screening participation included personal/cultural and provider/ system factors. Motivators included personal experience with others having cervical cancer, perceived importance of the Pap smear in maintaining health, reduction of financial barriers, and access to culturally appropriate health care. CONCLUSIONS: Factors affecting cervical cancer screening behavior among Hispanic women are identifiable and describable. Knowledge of barriers and motivators can be utilized to design effective nursing interventions and community-based programs.
Adolescent↗
Need for guidelines for screening in anal cancer: a lesson from cervical cancer.
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Anus Neoplasms↗
Tumor necrosis factor A and MHC class I chain related gene A (MIC-A) polymorphisms in Swedish patients with cervical cancer.
Human papillomaviruses type 16 and 18 are the major cause of cervical cancer. However, genetic factors contribute to the propensity of persistent HPV infection and cervical carcinoma. Allelic variants of the human leukocyte genes have shown to be associated with cervical neoplasia. The strongest associations have been found with the genes in the HLA class II region. The aim of this study was to analyze the association of two non-HLA class II markers with invasive cervical cancer. Microsatellite polymorphism of the TNFA gene located in the class III region and a short tandem repeat polymorphism of the MICA gene located in the centromeric end of the HLA class I region were analyzed. Eighty-five patients and 120 matched control individuals from a population-based cohort from Northern Sweden participated in this nested case-control study. MICA was not associated with cervical carcinoma. TNFa-11 frequency was increased in the HPV18 DNA positive patients (OR = 2.84, p = 0.0481, CI = 1.04-7.78, pc = NS). TNFa-11 was not associated with susceptibility to HPV16 infection, but it increased the risk for cervical cancer with the HLA DQ6 (DQA 1*0102-DQB 1*0602) haplotype. Our findings indicate that the association of TNFA with cervical cancer is different with CIN. The extended HLA DQ6-TNFa-11 haplotype is increasing the risk for development of cervical cancer significantly (OR = 3.08, p = 0.0104, CI = 1.30-7.31).
Adult↗