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PubMed2003

[Factors associated with non-participation in screening for cervical cancer in Southern Brazil].

Early detection of cervical cancer substantially increases the probability of cure. The aim of this study was to determine the prevalence and factors associated with non-participation in cervical cancer screening among women 15 to 49 years of age in Rio Grande, Southern Brazil. A representative survey was carried out using a systematic sample based on a census tract. Trained interviewers used standard, individualized, household questionnaires to interview the women. Data analysis used logistic regression according to a previously determined hierarchical framework. Among 1,302 women interviewed, 57% had never had a Pap smear. The risk factors most closely associated with non-participation in screening were black or brown skin color, young age, low family income, low schooling, living alone, and first childbirth after 25 years of age. Coverage for early detection of cervical cancer was very low. In addition, women at high risk of developing cervical cancer were shown to have a significantly higher risk of non-participation in this type of screening.

Adolescent↗
PubMedDate not supplied

Cervical cancer screening in Japan. A case-control study.

OBJECTIVE: To prove the effectiveness of mass screening for cervical cancer with the cervical cytologic smear in Japan. STUDY DESIGN: The cases consisted of 109 patients with invasive carcinoma who were identified by mass screening for cervical cancer between 1984 and 1989. For each case, two age-matched controls were chosen from females who underwent mass screening in the same district during the same period. The odds ratio (OR) for invasive cervical cancer and that of each histologic type for the previously screened vs. unscreened females were calculated. In addition, the OR for invasive cervical cancer according to the screening interval was calculated. RESULTS: The OR of invasive cervical cancer for the previously screened vs. unscreened females was significant (P < .16). According to the histologic type, the OR of squamous cell carcinoma for the previously screened vs. unscreened females was significant (P < .14), while that for adenocarcinoma was not significant (P < .45). According to screening interval, the OR for screening at a one- or two-year interval was significant (P < .11 and .33, respectively). CONCLUSION: This case-control study statistically showed the usefulness of screening for cervical cancer in Japan.

Adenocarcinoma↗
PubMed1990

A cohort analysis of cervical cancer in Israeli Jewish women.

The incidence of squamous cell cervical cancer was studied in Jewish Israeli women between 1961 and 1981. The 1052 cases and the 27,832,272 women-years of observation were divided according to continent-of-origin, year-of-birth, and immigration-wave cohorts. Age-adjusted odds ratios were calculated for each cohort and compared. The incidence of cervical cancer was shown to have changed according to cohort year of birth, most significantly in women born in Europe and America. The highest risk in this group was seen in women born in 1891-1895 and 1941-1945 and the lowest in women born between 1926 and 1935. A high risk was also observed in all cohorts of North African women. There was a sharp rise in risk for women of all origins born after 1940. Immigration to Israel at a younger age was correlated with reduced risk for cervical cancer. It has been shown that epidemics of sexually transmitted diseases (STDs) are followed in time by epidemics of cervical cancer. Since there was an epidemic of STDs in Israel between 1967 and 1970, our results also suggest that there is a rise in the risk for cervical cancer in women who were sexually active during the epidemic of STDs. Because of the low rates for cervical cancer traditionally observed in Israeli women, routine screening was not done in Israel in the past. Should the relative risk for cervical cancer in women exposed during the 1967-1970 epidemic continue to be high, screening may prove worthwhile.

Adult↗
PubMed2004

Molecular genetics of human cervical cancer: role of papillomavirus and the apoptotic cascade.

Cervical cancer is rated the second most common malignant tumour globally, and is aetiologically linked to human papillomavirus (HPV) infection. Here the cellular pathology under consideration of stem/progenitor cell carcinogenesis is reviewed. Of the three causative molecular mechanisms of cervical cancer, two are associated with HPV: firstly, the effect of the viral oncogenes, E6 and E7; and secondly, integration of the viral DNA into chromosomal regions of tumour phenotype. The third process involved is the repetitive loss of heterozygosity in some chromosomal regions. HPV can be classified into high- and low-risk types; the high-risk types encode two oncoproteins, E6 and E7, which interact with tumour suppressor proteins. The association results in the inactivation of tumour suppressor proteins and the abrogation of apoptosis. Apoptosis is referred to as programmed cell death, whereby a cell deliberately commits suicide, and thus regulates cell numbers during development and maintenance of cellular homeostasis. This review attempts to elucidate the role of apoptotic genes, and considers external factors that interact with HPV in the development and progression of cervical cancer. Therefore, an in-depth understanding of the apoptotic genes that control molecular mechanisms in cervical cancer are of critical importance. Useful targets for therapeutic strategies would be those that alter apoptotic pathways in a manner where the escape of HPV from surveillance by the host immune system is prevented. Such an approach directed at the apoptotic genes maybe useful in the treatment of cervical cancer.

Apoptosis↗
PubMed1996

Trends in cervical cancer mortality in the Americas.

This article presents an assessment of cervical cancer mortality trends in the Americas based on PAHO data. Trends were estimated for countries where data were available for at least 10 consecutive years, the number of cervical cancer deaths was considerable, and at least 75% of the deaths from all causes were registered. In contrast to Canada and the United States, whose general populations had been screened for many years and where cervical cancer mortality has declined steadily (to about 1.4 and 1.7 deaths per 100,000 women, respectively, as of 1990), most Latin American and Caribbean countries with available data have experienced fairly constant levels of cervical cancer mortality (typically in the range of 5-6 deaths per 100,000 women). In addition, several other countries (Chile, Costa Rica, and Mexico) have exhibited higher cervical cancer mortality as well as a number of noteworthy changes in this mortality over time. Overall, while actual declining trends could be masked by special circumstances in some countries, cervical cancer mortality has not declined in Latin America as it has in developed countries. Correlations between declining mortality and the intensity of screening in developed countries suggest that a lack of screening or screening program shortcomings in Latin America could account for this. Among other things, where large-scale cervical cancer screening efforts have been instituted in Latin America and Caribbean, these efforts have generally been linked to family planning and prenatal care programs serving women who are typically under 30; while the real need is for screening of older women who are at substantially higher risk.

Adult↗
PubMed1999

Risk factors for rapid-onset cervical cancer.

OBJECTIVES: The current study was designed to elucidate risk factors associated with the development of cervical cancer during the course of routine Papanicolaou smear screening (rapid-onset cervical cancer). STUDY DESIGN: Four hundred eighty-three women diagnosed with invasive cervical cancer, representing 73% of all such tumors diagnosed in Connecticut between 1985 and 1990, were studied. Papanicolaou smear screening and risk factor information was obtained by questionnaire and physician record review. Results from human papillomavirus deoxyribonucleic acid testing by polymerase chain reaction of tumor samples were available for 278 study participants. Prediagnostic Papanicolaou smear slides were reviewed for 67% of cases with a screening history. Screening history information, slide review, and questionnaire data were used to classify women as having rapid-onset cervical cancer (n = 43), possible rapid-onset cervical cancer (n = 111), or normal-onset cervical cancer (n = 329). RESULTS: Compared with normal-onset cases, rapid-onset cases tended to be younger (P =.001) and were more likely to be white (P =.002), diagnosed with adenocarcinomas or adenosquamous carcinomas (P =.001), and diagnosed with early-stage disease (P =.001). Cases diagnosed as possible rapid-onset disease tended to have a profile that was intermediate to that observed for rapid-onset and normal-onset cases. Human papillomavirus deoxyribonucleic acid was detected in 75.2% of cases tested. Compared with women who tested positive for human papillomavirus type 16 or other, those positive for human papillomavirus type 18 had a relative risk for rapid-onset disease of 1.6 (95% confidence interval 0.52-4.9). No significant association was observed between type 18 and possible rapid-onset disease when possible rapid-onset cases were compared with women diagnosed with normal-onset cervical cancer (relative risk 0.67, 95% confidence interval 0.29-1.6). Oral contraceptive use, cigarette smoking, number of pregnancies, and a maternal history of cervical cancer were not significantly associated with rapid-onset disease. CONCLUSIONS: Results from this study suggest that the risk factors associated with the development of rapid-onset cervical cancer are similar to those for normal-onset disease.

Adenocarcinoma↗
PubMed2005

Primary care physicians' awareness and adherence to cervical cancer screening guidelines in Texas.

BACKGROUND: Cervical cancer screening guidelines were created to help healthcare professionals in appropriate screening utilizing the PAP test. However, significant variation in cervical cancer screening among primary care physicians has been noted. Knowledge of the awareness of and adherence to cervical cancer screening guidelines by primary care physicians will help determine how best to disseminate and educate these physicians regarding the guidelines in hopes of reducing unnecessary screening and improving screening for under screened populations. METHODS: A cross-sectional, mailed survey involving Family Medicine (FP), Community Internal Medicine (CIM), and Obstetrics/Gynecology (OB) physicians practicing in a large University-affiliated, multi-specialty group practice associated with an 186,000-member HMO in Central Texas (n = 177) was conducted in 2001-2002. RESULTS: Most physicians performed PAP testing (50.4%). PAP screening was noted to vary significantly by specialty (P < 0.0001). All OBs were aware of at least one published guideline, compared to 96% of FPs and 91% of CIMs (P < 0.05). A wide variation was reported regarding adherence to published guidelines. In addition, there was significant intraspecialty variation regarding adherence to the physicians' own specialty's guidelines. CONCLUSIONS: While most physicians in the primary care setting perform PAP tests and are aware of published guidelines for PAP screening, adherence to the published guidelines varies considerably even in the same clinical setting.

Adult↗
PubMedDate not supplied

Homozygous arginine at codon 72 of p53 has no prognostic significance in cervical cancer.

Mutation of p53, a tumour suppressor gene, is uncommon in cervical cancer but the detection of human papillomavirus (HPV) DNA in cervical cancer is common. The findings of increased susceptibility to degradation of p53 by E6 protein of HPV16/18 in cervical cancer with homozygous arginine at codon 72 (HA72) of p53 led to this study on whether cervical cancers with HA72 were more aggressive with the increase in the rate of loss of p53 function. In 102 cervical cancers, 76.5% were HPV16/18 positive and 30% had HA72. No survival difference was detected between HA72 and non-HA72 tumours irrespective of HPV16/18 status. Furthermore, the detection of HPV16/18 in cervical cancer was found not to be of prognostic significance in this study.

Adenocarcinoma↗
PubMed1984

Genital warts and cervical cancer. III. Subclinical papillomaviral infection and cervical neoplasia are linked by a spectrum of continuous morphologic and biologic change.

Human papillomaviral (HPV) infection is now widely advanced as an important etiologic factor in cervical cancer. This study was undertaken to clarify morphologic relationships within the biologic spectrum linking subclinical papillomaviral infection (SPI) to cervical intraepithelial (CIN). Two pathologists analyzed 72 colposcopic biopsies, using a semi-objective rating scheme that scored 24 different histologic criteria. Each individual criterion was checked for reproducibility, and validated against an objective measure of papillomaviral infection (immunoperoxidase staining) or premalignant change (microspectrophotometry). The individual criteria were then combined into histologic indices of benign warty change, presumed viral atypia, abnormal cell phenotype, and disturbed tissue maturation. Histologic expression of papillomaviral infection decreased with increasing degrees of premalignant change. Plotting the index of abnormal cell phenotype against that of disturbed tissue maturation produced a linear plot in which cases clustered into four diagnostic groups. The histologic indices of papillomaviral infection displayed significant curvilinear correlations with genotypic distortion, benign warty change being maximal in the CIN 1 range and presumed viral atypia in the CIN 2 range. Disturbance of nuclear DNA content also increased with worsening diagnosis; diploidy being most common in SPI (67%), polyploidy in CIN 1 (59%), and aneuploidy in CIN 2 (65%) and CIN 3 (82%). Conversely, capsid antigen production decreased from 36% in SPI to 9% in CIN 3. Three aneuploid epithelia were immunoperoxidase positive. These inverse relationships between late viral expression and nuclear distortion fit experimental models of viral oncogenesis. The gradual transition and morphologic overlap between diagnostic groups support the postulate that SPI and CIN are a single disease spectrum, in which differences are those of degree rather than of kind.

Adolescent↗
PubMed1999

Determining costs of health care services for cost-effectiveness analyses: the case of cervical cancer prevention and treatment.

OBJECTIVES: To estimate costs for the prevention and treatment of cervical cancer based on resource utilization and to compare those costs to published estimates and to local charges and reimbursements. DESIGN: Cost estimates for cervical cancer prevention services were based on clinic staff time, use of specialized equipment and supplies, laboratory costs, and clinic overhead. Cost estimates for cervical cancer treatment were based on HMO expenditures for cervical cancer patients and control patients. These costs were adjusted for stage distribution and survival rates. Published cost estimates were obtained from a systematic review of the medical literature between 1990 and 1996. SETTING: Three family planning clinics (for prevention costs) and a staff-model HMO (for treatment costs). PATIENTS: For treatment costs: 98 cervical cancer patients and 133,058 female control patients, matched by age and chronic disease score. MAIN OUTCOME MEASURES: Estimated costs for prevention and treatment of cervical cancer. Cost-to-charge and cost-to-reimbursement ratios. RESULTS: Costs of cervical cancer prevention and treatment services have been determined using a variety of methods. We found substantial variation in these estimates, even for studies with similar methodologies. Detailed resource-based estimation suggests that prevention costs are generally lower than those previously published in the literature, whereas the costs of cervical cancer treatment are generally higher. CONCLUSIONS: It is practical and desirable to employ resource use-based estimates of medical costs in cost-effectiveness analyses. Failure to do so for cervical cancer may affect policy recommendations by understating the relative benefits of prevention programs.

California↗
PubMed2003

Circulating levels of insulin-like growth factor-II and IGF-binding protein 3 in cervical cancer.

OBJECTIVE: We aimed to further document that elevated levels of circulating insulin-like growth factor II (IGF-II) are associated with cervical cancer and to test the hypothesis that there may be an inverse association between IGF-II and IGF-binding protein 3 (IGF-BP3). METHODS: Serum IGF-II and IGF-BP3 levels were measured, using ELISA kits (Diagnostic Systems Laboratories), in 23 controls; 16 ASC-US with normal biopsies; 14 ASC-US with advanced CIN; 2 pretherapy CIN-I; 8 successfully treated CIN-I; 24 persistent CIN I; 14 pretherapy CIN II/III; 10 posttherapy CIN II/III with normal biopsies; 18 persistent CIN-II/III; 7 with pretherapy cervical cancer; 19 with posttherapy cervical cancer under remission; 15 with posttherapy persistent/recurrent cervical cancer; 10 with persistent ovarian or endometrial cancer; and 3 with endometrial or vulvar with cervical cancer. Student's t test and linear regression analysis were used. RESULTS: Compared to controls (493 +/- 90 ng/ml) and women with other gynecological cancers, serum IGF-II levels were significantly increased in women with ASC-US, with advanced CIN on biopsy (P < 0.0001), persistent CIN-I (993 +/- 262 ng/ml; P < 0.0001), pretherapy advanced CIN (1086 +/- 240; P < 0.0001), pretherapy cervical cancer patients (1746 +/- 318 ng/ml; P < 0.0001) and posttherapy persistent/recurrent CIN (1094 +/- 300; P < 0.0001); and cervical cancer (1395 +/- 189; P < 0.0001). After therapy, the IGF-II levels returned to normal in both CIN and cervical cancer patients under remission. Elevated serum IGF-II levels had 100% sensitivity and 87% specificity for cervical cancer and 81% sensitivity and 82% specificity for CIN. The levels of IGF-BP3 were significantly reduced in women with CIN before and after therapy (P < 0.0001) and in cervical cancer patients before and after therapy (P < 0.001). There was an inverse relationship between serum IGF-II and BP-3 levels (P < 0.01). Decreased serum IGF-BP3 levels had a sensitivity of 72% and specificity of 75% for cervical cancer and 81% sensitivity and 83% specificity for CIN. When both markers were considered together the sensitivity was 72% and specificity 84% for cervical cancer, while for CIN, the sensitivity was 57% and specificity 81%. CONCLUSION: Serum IGF-II may be a reliable marker for early diagnosis and monitoring therapy efficacy (sensitivity and specificity of 100% versus normal controls), while IGF-BP3 levels can be reliably used to predict prognosis.

Biomarkers, Tumor↗
PubMed2004

hTERT-promoter-based tumor-specific expression of MCP-1 effectively sensitizes cervical cancer cells to a low dose of cisplatin.

Cervical cancers at advanced stages or with recurrent status are mainly treated by platinum-based chemotherapy, such as cisplatin. However, a novel strategy to reduce the minimally effective dose is required to prevent severe adverse effects that limit the effectiveness of the treatment. Monocyte chemoattractant protein-1 (MCP-1) is a subtype of chemokines that can promote monocyte/macrophage infiltration and enhance their phagocytosis at not only sites of inflammatory lesions but also of tumors. The present study applies MCP-1-based gene therapy to treat cervical cancers. To achieve tumor-specific expression of MCP-1, retroviral expression vector was constructed using the human telomerase reverse transcriptase gene (hTERT) promoter. Retroviral expression of MCP-1 into cervical cancer ME180 cells did not affect their proliferation either in vitro or in vivo. However, when combined with a suboptimal low dose of cisplatin, tumor formation was obviously reduced in clones transduced with MCP-1, but not in control clones. Histological examination revealed that a substantial number of macrophages infiltrated the tumor sites of MCP-1-transduced cells, but not of controls. These findings suggest that MCP-1 expression sensitizes cervical cancer cells to an otherwise ineffective low dose of cisplatin, possibly by inducing the migration of macrophages to eradicate tumor cells. This system may be a novel strategy for chemotherapy combined with immunogene therapy against otherwise intractable cervical cancers.

Animals↗
PubMed2006

Alternative technologies in cervical cancer screening: a randomised evaluation trial.

BACKGROUND: Cervical cancer screening programmes have markedly reduced the incidence and mortality rates of the disease. A substantial amount of deaths from the disease could be prevented further by organised screening programmes or improving currently running programmes. METHODS/DESIGN: We present here a randomised evaluation trial design integrated to the Finnish cervical cancer screening programme, in order to evaluate renewal of the programme using emerging technological alternatives. The main aim of the evaluation is to assess screening effectiveness, using subsequent cancers as the outcome and screen-detected pre-cancers as surrogates. For the time being, approximately 863,000 women have been allocated to automation-assisted cytology, human papillomavirus (HPV) DNA testing, or to conventional cytology within the organised screening programme. Follow-up results on subsequent cervical cancers will become available during 2007-2015. DISCUSSION: Large-scale randomised trials are useful to clarify effectiveness and cost-effectiveness issues of the most important technological alternatives in the screening programmes for cervical cancer.

Adult↗
PubMed2005

Expression of survivin, cyclinD1, p21(WAF1), caspase-3 in cervical cancer and its relation with prognosis.

The implications of Survivin, CyclinD1, p21(WAF1), Caspase-3 in the development, progression and prognosis in cervical cancer were investigated. By using immunohistochemical SP method, the expression of Survivin, CyclinD1, p21(WAF1), Caspase-3 was detected in 41 cases of cervical cancer, 17 cases of cervical intraepithelial neoplasia (CIN) and 10 cases of normal tissues, and their relation with pathological grade, clinical stage, metastasis and survival time was analyzed. The results showed that the positive expression rate of Survivin, CyclinDl in cervical cancer was significantly higher than in CIN group and normal control group (P < 0.05). The median survival time in the patients with cervical cancer positive for Survivin and CyclinD1 was significantly shorter than in those with negative expression (P < 0.05). The expression of both Survivin and CyclinD1 was not related with tumor grade, clinical stage and metastasis (P > 0.05). The positive expression rate of p21(WAF1) , Caspase-3 in cervical cancer was significantly lower than in CIN group and normal control group (P < 0.05), and had a close relation with tumor grade (P <0.05). The expression of Survivin in cervical cancer in cervical cancer was negatively associated with that of Caspase-3 (P < 0.01), but positively with that of CyclinD1 (P < 0.01). Cox Multivariate analysis revealed that Survivin was the independent prognostic indicator influencing the survival time of the patients with cervical cancer (P < 0.05). It was suggested that the high expression of Survivin or CyclinD1, and low expression of p21(WAF1) or Caspase-3 was closely correlated with the development of cervical cancer. Survivin and CyclinD1 could be used as a useful indicator to predict the prognosis of cervical cancer.

Adenocarcinoma↗
PubMed1996

[Ovarian metastasis in uterine cervical cancer: analysis of 17 cases].

OBJECTIVE: To investigate the incidence of ovarian metastasis in cervical cancer, especially in early FIGO stages. METHODS: Seventeen cervical cancer patients with ovarian metastasis treated at Cancer Hospital, Chinese Academy of Medical Sciences from 1958 to 1994 were retrospectively analysed. The diagnoses of all patients were confirmed by operations and pathologic examinations. RESULTS: The incidence of ovarian metastasis in cervical cancer was 0.07% in squamous cell carcinoma and 1.81% in adenocarcinoma (P < 0.05). In early stages (stage l-I), the incidence of ovarian metastasis in adenocarcinoma was higher than that in squamous cell carcinoma (2.2% VS 0.08%, P < 0.05). In patients treated by surgery, the rate of ovarian metastasis in adenocarcinoma was also higher than that in squamous cell carcinoma (7.8% VS 1.6%, P < 0.05). 10 of the 17 cases had macroscopic metastasis and 7 had microscopic metastasis. 11 patients (58.8%) were with bilateral ovarian involvement. Uterine corpus invasion and retroperitoneal lymph node involvements were high risk factors for ovarian metastasis in cervical cancer. The prognosis of cervical cancer patients with ovarian metastasis was poor, the 5-year survival rate in this study being only 17.6%. CONCLUSIONS: Patients with cervical cancer are threatened with the risk of ovarian metastasis, especially in adenocarcinoma. Conservative treatment of the cervical cancer with reservation of the ovary should be further investigated.

Adenocarcinoma↗
PubMed1997

Social differences in sexual behaviour and cervical cancer.

In this chapter we first describe the variation of cervical cancer in relation to social class. Thereafter we examine the causes for the occurrence of socioeconomic differences in invasive cervical cancer, using data from two case-control studies carried out in Colombia and Spain. Cervical cancer is the most common cancer in developing countries and the sixth most common in developed countries. In all areas, it is more frequent among women of low socioeconomic status, it is associated with multiple sexual partners and early age at first sexual intercourse, and both incidence and mortality are reduced by screening. According to population-based surveys in industrialized countries, men of low socioeconomic status report fewer sexual partners than men of high socioeconomic status but there is no clear indication that the same is true of women of low socioeconomic status. In the case-control studies in Spain and Colombia, the human papillomavirus and all other sexually transmitted diseases were more prevalent among women in low socioeconomic strata. Number of sexual partners and particularly contacts with prostitutes were higher among husbands of women of low socioeconomic status. Other potential risk factors for the disease, such as smoking and oral contraceptive use, and also cervical cancer screening (Pap smears), were more common in women of high social strata. Women with no schooling had a threefold higher risk in Spain and a fivefold higher risk in Colombia of having cervical cancer compared with women who had achieved a higher educational level. After adjustment for sexual behaviour, HPV DNA status, history of Pap smears and husband's contact with prostitutes, this association was considerably reduced. These results are indicative that socioeconomic differences in the incidence of cervical cancer can be partly explained by differences in the prevalence of HPV DNA. Men's sexual behaviour and particularly contacts with prostitutes might be a major contributor to the higher prevalence of HPV DNA among the poor.

Adolescent↗
PubMed1995

Occurrence of the antibody against human papillomavirus type 16 virion protein L2 in patients with cervical cancer and dysplasia.

Infection with HPV 16 is believed to be a major risk factor for cervical cancer. To correlate HPV 16 infection and carcinogenesis in the cervix, we examined by ELISA 326 sera from healthy females and patients with cervical cancer, cervical intraepithelial neoplasia, or dysplasia, for the presence of IgG antibodies against HPV 16 virion protein L2 expressed in Escherichia coli. Whereas 2 of 208 were positive in the healthy females, 4 of 23 and 6 of 90 were positive in the patients with cervical cancer and dysplasia, respectively. The findings indicate that infection with HPV 16 is related to cancer and dysplasia of the cervix. The anti-L2 antibody did not occur coincidentally with the antibodies against the HPV 16 early proteins E4 and E7, which are specifically but independently associated with patients with cervical cancer.

Adolescent↗
PubMed2004

p73 expression is associated with the cellular radiosensitivity in cervical cancer after radiotherapy.

Apoptosis is one of the causes of cell death in cervical cancer following radiotherapy. By studying the gene expression profile with cDNA apoptotic array, the p73 gene was found overexpressed in radiosensitive cervical cancers when compared with radioresistant ones. To investigate the role of the p73 gene in relation to clinical assessment of radiosensitivity in cervical cancer based on the findings of residual tumor cells in cervical biopsies after completion of radiotherapy, we studied the protein expression of p73 in 59 cervical cancers after radiotherapy and 68 normal cervices using immunohistochemistry. The expression of p73 was found to be significantly increased in cancer samples and, more importantly, in those samples sensitive to radiotherapy (P < 0.001). The overexpression of p73 actually predicted a better prognosis in cervical cancer patients (P < 0.001). To investigate the possible involvement of p73 downstream genes, the protein expressions of p21 and Bax were studied. The expression of p21, but not Bax, was found to be positively correlated with the expression of p73 (P = 0.001). Furthermore, the epigenetic regulation of p73 expression via DNA methylation was also investigated in 103 cervical cancers and 124 normals. Hypermethylation of p73 gene was observed in 38.8% of cervical cancers, and it was significantly associated with reduced or absent p73 expression (P < 0.001). Reactivation of p73 expression in two cervical cancer cell lines by demethylation treatment supported the role of methylation in the regulation of p73 expression. Our findings suggested that p73 expression was related to the radiosensitivity of cervical cancer cells and may play an important role in the regulation of cellular radiosensitivity.

Adult↗