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Background: A phase III trial was conducted to determine whether neoadjuvant chemotherapy (NACT) before radical surgery (RS) improves overall survival., Methods: Patients with stage IB2, IIA2, or IIB squamous cell carcinoma of the uterine cervix were randomly assigned to receive either BOMP (bleomycin 7 mg days 1-5, vincristine 0.7 mg m(-2) day 5, mitomycin 7 mg m(-2) day 5, cisplatin 14 mg m(-2) days 1-5, every 3 weeks for 2 to 4 cycles) plus RS (NACT group) or RS alone (RS group). Patients with pathological high-risk factors received postoperative radiotherapy (RT). The primary end point was overall survival., Results: A total of 134 patients were randomly assigned to treatment. This study was prematurely terminated at the first planned interim analysis because overall survival in the NACT group was inferior to that in the RS group. Patients who received postoperative RT were significantly lower in the NACT group (58%) than in the RS group (80%; P=0.015). The 5-year overall survival was 70.0% in the NACT group and 74.4% in the RS group (P=0.85)., Conclusion: Neoadjuvant chemotherapy with BOMP regimen before RS did not improve overall survival, but reduced the number of patients who received postoperative RT.

Background: The present study was conducted to determine the frequency and clinicopathological features of ovarian metastasis in a large population of patients with stage Ib-IIb cervical cancer., Methods: The study population consisted of 3471 patients with stage Ib to IIb cervical cancer who underwent radical hysterectomy, including pelvic lymphadenectomy and bilateral salpingo-oophorectomy, at our six institutions between 1981 and 2000. To our knowledge, this study is the largest review of patients with ovarian metastasis from cervical cancer. We reviewed the patients' medical records to determine clinicopathological features., Results: Fifty-two patients (1.50%) had ovarian metastases: 6 in stage Ib1, 12 in stage Ib2, 5 in stage IIa, and 29 in stage IIb. The mean age of patients with ovarian metastasis was 49.9 years (range: 29-73 years). The incidence of ovarian metastasis in patients with cervical cancer was 0.22% for stage Ib, 0.75% for stage IIa, and 2.17% for stage IIb with squamous cell carcinoma, and 3.72%, 5.26%, and 9.85%, respectively, in adenocarcinoma. Ovarian metastasis occurred more frequently among patients with adenocarcinoma than among those with squamous cell carcinoma (5.31% vs. 0.79%). Outcome for patients with ovarian metastasis was very poor and not related to FIGO stage and histological type. The presence of ovarian metastasis did not correlate with lymph node involvement or parametrial invasion., Conclusion: Study results indicate that ovaries can be preserved in patients with stage Ib-IIa squamous cell carcinoma but removed in all patients with adenocarcinoma.

Objective: In this study, genetic polymorphisms, XRCC1 Arg399Gln and OGG1 Ser326Cys were examined with reference to cervical cancer risk in a population-based incident case-control study in Japan., Methods: The cases comprised 131 cervical cancer patients: 87 cases with squamous cell carcinoma (SCC) and 44 with adenocarcinoma (ADC) or adenosquamous carcinoma (ADSC). Controls were sampled from 320 healthy women who underwent a health checkup., Results: The frequency of the XRCC1 399GlnGln genotype was higher in individuals with adenocarcinoma/adenosquamous carcinoma than in the healthy controls (OR = 2.98, 95% CI = 1.11-8.01, P = 0.030). However, no association was demonstrated in SCC. Analysis of OGG1 Ser326Cys polymorphism showed no significant differences between cervical cancer patients and controls. In stratification analysis, significant elevated risk of adenocarcinoma/adenosquamous carcinoma was associated with the XRCC1 399GlnGln genotype among nonsmokers (OR = 3.85, 95% CI = 1.28-11.59, P = 0.017), but not among smokers. No gene-gene interaction was observed in our case subjects., Conclusion: This is the first report that the XRCC1 Arg399Gln polymorphism might be important in relation to the risk of adenocarcinoma/adenosquamous carcinoma of the cervix.

Doses of nedaplatin (CDGP) were established for concurrent chemoradiation therapy (CCRT) for cervical cancer, and a collaborative dose escalation study involving 8 hospitals was conducted to investigate the safety and efficacy of this therapy. Radiotherapy was performed according to the standard treatment described in the Regulations of Cervical Carcinoma Treatment. CDGP at 80 mg/m2 as Level 1 or at 90 mg/m2 as Level 2 was administered on Days 1 and 29 of treatment. Dose-limiting toxicity (DLT) was observed in 1 of 6.patients receiving 80 mg/m2 of CDGP and in all 2 patients receiving 90 mg/m2 of CDGP; therefore, Level 2 was regarded as the maximum tolerated dose (MTD), and Level 1 as the recommended dose. DLT signs consisted of delayed improvement in the leukocyte count in 2 patients and anorexia in 1 patient, suggesting that delayed improvement in the leukocyte count is the main DLT of this combination therapy. The main side effects were digestive disorders such as nausea and anorexia and bone marrow suppression, such as leukopenia, neutropenia, and thrombopenia. Side effects in the Level 1 group were more mild than in the Level 2 group. The efficacy was PR or better in all patients. The CR rates were 60% (6/10) in the Level 1 group and 50% (1/2) in the Level 2 group; there was no marked difference between the two groups. These results suggest that CCRT involving administration of CDGP at 80 mg/m2 on Days 1 and 29 is safe and effective.

Objective: In this study, genetic polymorphisms, NQO1 C609T, GSTM1 positive/null, and GSTT1 positive/null, were examined with reference to cervical cancer risk in a population-based incident case-control study in Japanese., Methods: The cases comprised 131 cervical cancer patients: 87 cases with squamous cell carcinoma (SCC) and 44 with adenocarcinoma (ADC) or adenosquamous carcinoma (ADSC). Controls were sampled from 320 healthy women who underwent a health checkup., Results: The cervical cancer risk was substantially elevated with smoking for all cases, SCC cases, and ADC/ADSC cases (OR = 4.50, 95% CI = 2.48-8.17, P < 0.001; OR = 5.68, 95% CI = 2.99-10.78, P < 0.001; and OR = 2.57, 95% CI = 1.09-6.08, P = 0.032; respectively). The frequency of the NQO1 609TT genotype, reported to be associated with null enzyme activity, was higher in individuals with all cases and SCC than in the healthy controls (OR = 1.97, 95% CI = 1.06-3.66, P = 0.032; and OR = 2.42, 95% CI = 1.21-4.82, P = 0.012; respectively), but not in ADC/ADSC cases. Analysis of polymorphisms for GSTM1 and GSTT1 showed no significant differences between cervical cancer patients and controls. In stratification analysis, significant elevated risk of all cases and SCC was associated with the NQO1 609TT genotype among nonsmokers (OR = 2.15, 95% CI = 1.08-4.30, P = 0.030; and OR = 2.83, 95% CI = 1.21-6.31, P = 0.011; respectively), but not smokers. No gene-gene interaction was observed in our case subjects., Conclusion: This is the first report that the NQO1 gene might be important in relation to the risk of squamous cell carcinoma of the cervix.

To examine the possible association between cervical cancer and Lymphotoxin-alpha (LT(alpha)) polymorphisms, C804A and A252G, an incident case-control study was conducted in Japanese. The cases were 131 cervical cancer patients. Controls were 320 healthy women. Risk estimation was conducted by an unconditional logistic model. Complete linkage disequilibrium was seen between LT(alpha) C804A and LT(alpha) A252G. We found that, compared with the 804CC genotype, 804CA and 804AA were associated with a decreased risk of cervical cancer (OR = 0.64, 95% CI = 0.40-1.02; and OR = 0.45, 95% CI = 0.21-0.95, respectively), especially of SCC (OR = 0.54, 95% CI = 0.32-0.91; and OR = 0.39, 95% CI = 0.16-0.92, respectively).

The conventional local treatment methods (surgery and radiation) for cervical cancer have reached a plateau in terms of survival benefit and, therefore, in this review, new treatment strategies (combined chemotherapy [CT] and local therapy) to overcome the poor prognosis were examined in high-risk groups. The effectiveness of neoadjuvant chemotherapy (NAC) administered prior to radiotherapy (RT) has not been confirmed for any disease stages. But NAC followed by surgery may improve survival in patients with stage Ib2 compared with surgery alone; and in patients with stage Ib2 to IIB compared with RT alone. Five large randomized clinical trials (RCTs) demonstrated a significant survival benefit for patients treated with concurrent chemoradiotherapy (CCRT), using a cisplatin (CDDP)-based regimen, with a 28%-50% relative reduction in the risk of death. In addition, the results of a metaanalysis of 19 RCTs of CCRT (1981-2000) involving 4580 patients showed that CCRT significantly improved overall survival (OS) hazard ratio ([HR] 0.71; P < 0.0001), as well as progression-free survival (PFS; HR 0.61; P < 0.0001). In line with these results, CCRT is currently recommended as standard therapy for advanced cancer (stage III/IVA) in the United States. However, there remains much controversy and uncertainty regarding the optimal therapeutic approaches, especially for patients with advanced cancer. Additional RCTs should be conducted to find the optimal CT regimen and RT for Japanese patients, considering acute and late complications, as well as differences in pelvic anatomy, total radiation dose, and RT procedures between Japan and other countries. Evidence obtained from such studies should establish the optimal CCRT treatment protocol and define the patient population (disease stage) that the protocol really benefits.

Endocrine tumor of the uterine cervix is rare, as only nine cases have been reported as patients who troubled by the ectopically endocrine hormone. Five of these patients afflicted by ectopic ACTH secretion which caused Cushing's syndrome, two suffered by insulin which resulted hypoglycemia, one distressed by PTH, and the other troubled by G-CSF. Seven of the nine patients were diagnosed histologically as small cell carcinoma, which was famous for neuroendocrine tumor, high incidence of vascular invasion and lymph node involvement, clinical behavior of hematogenously dissemination, and poor prognosis. Age of six patients was less than 50 years old, and metastatic tumor was confirmed in six of the nine patients.

Background: This study evaluated the results of resection of pulmonary metastases from cervical cancer., Methods: A total of 7,748 patients with primary stage Ib or II cervical cancer underwent curative initial treatment consisting of radical hysterectomy or radiotherapy in 22 hospitals. Of the 7,748 patients, 29 (0.37%) patients had pulmonary metastases, which were detected after a disease-free period after initial treatment (radical hysterectomy or radiotherapy) and were resected with the intention to cure by June 30, 1998., Results: The 5-year disease-free survival rate after pulmonary metastasectomy for all patients was 32.9%. Patients with one or two pulmonary metastases had a 5-year disease-free survival rate of 42.2% compared with 0% for patients with three or four metastases (p = 0.0003). Patients with squamous cell cancers had a 5-year disease-free survival rate of 47.4% compared with 0% for patients with adenosquamous cell cancers or adenocarcinoma (p = 0.0141). On multivariate analysis, the significant prognostic variables for disease-free survival were two or fewer metastases (p = 0.0232) and squamous cell cancer (p = 0.0168)., Conclusions: Cervical cancer patients with pulmonary metastases after initial treatment (radical hysterectomy or radiotherapy) could expect to achieve long-term disease-free survival by pulmonary metastasectomy when there are two or fewer metastases diagnosed as squamous cell cancer.

We performed retrospective analysis to classify the risk hazard of patients with stage I-II cervical cancer with lymph node metastases treated with postoperative radiotherapy. From 1981 to 1995, 106 patients with early stage cervical carcinoma who received adjuvant pelvic radiation were entered in the analysis. The median patient age was 53.0 years (range 21-73). The median dose of 45.3 Gy (range, 32.1-56.4 Gy) was delivered over the whole pelvis. Seventy patients also received prophylactic paraaortic radiation (median 44 Gy; range 22-46 Gy). The 5/10-year overall survival (OAS), disease-free survival (DFS), pelvic control, and distant metastasis-free survival rates were 69.1/63.5%, 62.4/58.1%, 85.7/84.3%, and 74.1/71.6%, respectively. In the uni-/multivariate analyses, the significant prognostic factors of OAS and DFS proved to be disease stage, duration period between operation and radiotherapy, histology, and presence or absence of common iliac lymph node metastasis. Using the results of these analyses, we devised a predictive model for DFS. In this model, the 5-year DFS rates of patients with low (N = 35), intermediate (N = 59), and high-risk factors (N = 12) were 88.1%, 56.7%, and 16.7%, respectively (p < 0.0001). The majority of analyzed patients did not have adequate DFS estimates in this series. High-risk patients should receive a more intensive strategy, such as concurrent chemoradiotherapy. On the other hand, the effort to reduce toxicity should be considered carefully.

To examine the possible association between cervical cancer and p73 G4C14-to-A4T14 in exon 2 and p53 Arg72Pro polymorphisms, an incident case-control study was conducted in Japanese. The cases were 112 cervical cancer patients. Controls were 320 healthy women and 122 non-cancer female outpatients. Risk estimation for each genotype by an unconditional logistic model demonstrated a possible association between the p73 A4T14 variant and the risk of cervical cancer in our Japanese population (OR = 1.57; 95%CI, 0.99-2.48, P = 0.053). There was no significant difference in the p53 Arg72Pro genotype frequency between the controls and cases.

To evaluate the ability of magnetic resonance imaging (MRI) to predict the clinical outcome, we perform retrospective multicenter analysis of patients with stage III disease treated with radiation alone. From three institutions, 80 patients with stage III disease diagnosed with MRI were entered in the study. Seventy-eight patients received intracavitary brachytherapy with external beam radiotherapy. Univariate and multivariate analyses were performed to identify the prognostic factors for overall survival (OAS), disease-free survival (DFS), pelvic control (PC), and distant metastasis-free survival (DMFS). The 5-year OAS, DFS, PC, and DMFS rates were 59.5%, 48.7, 74.2%, and 62.5%, respectively. Bilateral pelvic fixation to the pelvis (p = 0.001) and patient age 50 years or less (p < 0.0001) were significant adverse factors for OAS. As a function of DFS, these were positive lymph nodes (p = 0.02), bilateral fixation to the pelvis (p = 0.03), and younger patient age (p < 0.0001), respectively. Patient age 50 years or less proved to be the only significantly unfavorable factor for PC (p < 0.0001). Larger size/volume (p < 0.05), positive lymph nodes (p = 0.03), bilateral pelvic disease (p = 0.02), and younger patient age (p = 0.004) were significantly adverse factors for DMFS. Using multivariate analysis, patient age 50 years or less, disease with bilateral fixation, and calculated volume more than 100 ml proved to be significantly adverse factors for OAS and DFS. In the analysis of PC, only patient age 50 years or less was a significantly adverse factor (p = 0.0014, relative risk [RR] = 14.93). Bilateral fixation to the pelvis (p = 0.0055, RR = 4.032), positive lymph nodes (p = 0.0494, RR = 2.637), and large calculated volume (>100 ml; p = 0.0057, RR = 4.831) proved to be significantly adverse factors for DMFS. For patients with stage III disease, size/volume and lymph node status derived from MRI showed a significant correlation with the development of distant metastasis, but failed to predict locoregional control. In addition, size/volume analysis showed no apparent relationship with disease-free survival. For patients with stage III disease, MRI may provide beneficial information predicting distant metastasis, but not for local control.

Purpose: To compare the efficacy of MRI and FIGO stage, we performed retrospective multicenter analysis of patients with Stage II-III disease treated with radiation alone., Methods and Materials: From three institutions, 164 patients diagnosed with cervical carcinoma were entered into the study. The majority of this cohort received intracavitary brachytherapy combined with external beam radiotherapy (n = 161). Uni- and multivariate analyses were performed to identify the prognostic factors for overall survival (OAS), disease-free survival (DFS), pelvic control (PC), and distant metastasis-free survival (DMFS)., Results: The 5-year OAS, DFS, PC, and DMFS rates were 68.8%, 60.4%, 77.4%, and 71.7%, respectively. Using uni- and multivariate analyses, both large tumor size/volume and positive lymph node enlargement (LN) showed a significantly unfavorable influence on survival and local and/or distant failure (p < 0.05). Using these two prognostic factors, patients were divided into three subgroups; the 5-year DFS rates of patients with risk 0 (volume 50 cc or positive LN), and 2 (volume >50 cc and positive LN) were 72.9%, 53.3%, and 26.1%, respectively (p < 0.0001). Among patients with volume 0.05)., Conclusion: MRI will provide more useful and practical information than will FIGO stage classification for patients with bulky disease, although this will remain a prognostic factor for patients with nonbulky disease (volume

Background: We performed retrospective analysis to evaluate the outcomes of postoperative radiotherapy for patients with cervical carcinoma without lymph node metastasis., Methods: From 1981 to 1995, 68 stage I-II cervical carcinoma patients without nodal disease who received adjuvant pelvic radiotherapy were entered into the present analysis. Criteria for postoperative radiotherapy were (1) deep stromal invasion (> or = 1/2; n = 63), (2) positive parametrial invasion (n = 38) and (3) close or positive surgical margin (n = 21). The median patient age was 54.0 years (range, 29-69 years). The median dose of 45.3 Gy (range, 43.4-56.4 Gy) was delivered over the whole pelvis median 21.0 days (range 12-68 days) after surgery., Results: The 5/10-year overall survival, disease-free survival, pelvic control and distant metastasis-free survival rates were 89.7/85.7, 85.3/83.2, 95.5/95.5 and 90.7/90.7%, respectively. Histology of adenocarcinoma (n = 4), large tumor size and prolonged period between operation and radiotherapy were significantly adverse prognostic factors of overall and disease-free survival by univariate analysis. The risk score referred from the GOG report correlated well with disease-free survival (P = 0.018), but showed only a tendency for overall survival as a prognostic factor (P = 0.07). Overall treatment time proved to be a significant variable for overall survival (P = 0.02), but not for disease-free survival (P = 0.056). Both risk score and overall treatment time proved to be significant prognostic factors in the multivariate model. Major adverse effects occurred in three patients (4.4%) without mortality., Conclusions: In this analysis, clinical outcome from adjuvant postoperative radiotherapy was thought to be feasible with both satisfactory pelvic control and acceptable lower toxicity.

Purpose: From recent randomized trials, patients with Stage II cervical carcinoma are thought to be candidates for chemoradiotherapy. To refine the strategy for Stage II patients, we performed a retrospective multi-institutional analysis using MRI., Methods and Materials: From three institutions, 84 patients with Stage II cancer diagnosed by MRI were entered into the study. All patients received intracavitary brachytherapy with (n = 83) or without (n = 1) external beam radiotherapy. Uni- and multivariate analyses were performed to identify the prognostic factors for overall survival (OAS), disease-free survival (DFS), pelvic control (PC), and distant metastasis-free survival (DMFS)., Results: The 5-year DFS rate of patients with maximal tumor size (D(max)) > or =50 mm (46.2%) was significantly lower than that for patients with D(max) <50 mm (88.0%; p <0.0001). Large size or volume and lymph node swelling were also significant prognostic factors of OAS, DFS, PC, and DMFS. In the multivariate model, size or volume was a significant prognostic factor of OAS, DFS, PC, and DMFS, and lymph node swelling was a prognostic factor for DFS, PC, and DMFS. Using these two prognostic factors, patients were divided into 3 subgroups. The 5-year DFS rate of patients with risk 0 (D(max) <50 mm and negative lymph node swelling), 1 (D(max) > or =50 mm or positive lymph node swelling), and 2 (D(max) > or =50 mm and positive lymph nodes) was 93.2%, 53.3%, and 25.0%, respectively (p <0.0001)., Conclusion: In this stage-limiting analysis, we clarified the stratification according to clinical risk with the aid of MRI. For patients with low-risk factors, especially for elderly patients, radiation alone would probability be a feasible option. In the future, a randomized trial using criteria with MRI would help to identify the optimal strategy for patients with Stage II disease.

Objective: The purpose of our study was to investigate a possible difference in ovarian metastasis between squamous cell carcinoma and adenocarcinoma of the uterine cervix and to confirm clinicopathological variables associated with the metastases., Methods: Clinical and pathological variables of 1064 patients with invasive squamous cell carcinoma and 240 with adenocarcinoma were studied., Results: Ovarian metastasis was found in 14 patients (1.3%) with squamous cell carcinoma and 15 (6.3%) with adenocarcinoma. The mean age of patients with ovarian metastasis of squamous cell carcinoma was 57.4 years, compared to 50.2 years for adenocarcinoma. Ovarian metastasis of adenocarcinoma was more likely to be visible (40.0%) and present in both ovaries (66.7%), while these two characteristics occurred in only 21.4 and 36.7% of patients with squamous cell carcinoma. A logistic regression analysis with clinical variables indicated that clinical stage beyond IIb was a significant variable of squamous cell carcinoma, and more than 30-mm tumor size was significant in adenocarcinoma., Conclusion: The incidence of ovarian metastasis of adenocarcinoma of the uterine cervix was significantly higher than that of squamous cell carcinoma. The incidence of adenocarcinoma was associated more closely with tumor size than clinical stage, whereas it was more associated with clinical stage in squamous cell carcinoma. The results thus suggested that the differences in ovarian metastases were caused by the different characteristics of the two types of carcinoma., (Copyright 2001 Academic Press.)

Objectives: The influence of the histology of adenocarcinoma on recurrence and survival for patients treated with radical hysterectomy and diagnosed as having pathologic stage Ib cervical cancer was investigated., Methods: Five hundred and nine patients (405 squamous cell carcinomas, 104 adenocarcinomas) with pathologic stage Ib cervical cancer treated initially at the Aichi Cancer Center between 1976 and 1995 were studied., Results: Multivariate analysis identified the prognostic variables as histology of adenocarcinoma, number of lymph nodes involved, and tumor size beyond 4 cm. Five-year overall survival and disease-free survival of patients with adenocarcinoma in the presence of lymph node metastasis were 63.2 and 47.4%, respectively, significantly poorer than for squamous cell carcinoma (83.6 and 80.6%; P < 0.001 and P = 0.002, respectively). These were not different in the absence of lymph node metastasis (adenocarcinoma, 93.9 and 92.7%; squamous cell carcinoma, 97.9% and 96.1%; P = 0.067 and P = 0.250, respectively)., Conclusions: The independent significant risk factors for the recurrence and survival of pathologic stage Ib cervical cancer were the presence of lymph node metastasis, large tumor size beyond 4 cm, and histology of adenocarcinoma. The prognosis of patients with adenocarcinoma was poorer than of patients with squamous cell carcinoma in the presence of lymph node metastasis, while the prognosis of pathologic stage Ib cervical cancer was equivalent when there was no metastasis., (Copyright 2000 Academic Press.)

Objective: The prognostic importance of adenocarcinoma of the uterine cervix was investigated. Methods. One hundred ninety-three patients (144 had stage I disease, 41 stage II, and 8 stage III-IV) with invasive adenocarcinoma of the uterine cervix treated initially at the Aichi Cancer Center between 1964 and 1995 were studied., Results: Of all the invasive cervical cancers, 8.8% were adenocarcinomas that had been increasing during the past decade. The overall 5-year survival for stage I was 88.8%, stage II 44.9%, and stage III-IV 0% In univariate analysis, the clinicopathological factors associated with overall survival and disease-free survival were age of patient, stage of disease, presence of nodal metastasis, number of lymph nodes involved, lymph-vascular space invasion, tumor size, and intraperitoneal metastasis. Multivariate analysis performed in all cases identified the clinical stage of disease, the presence of nodal metastasis, number of lymph nodes involved, lymph-vascular space invasion, and tumor size as the independent risk factors for recurrence and survival. In the analysis of stage I disease, lymph node metastasis and tumor size were the significant prognostic factors, while lymph-vascular space invasion and tumor size were the factors in advanced disease. Tumor grade and histological type were not associated with recurrence and survival., Conclusion: These results suggested the association of lymph node metastasis with the prognosis of early stage adenocarcinoma of the uterine cervix and lymph-vascular space invasion with the advanced stage. Tumor size was an independent risk factor throughout all stages., (Copyright 1999 Academic Press.)

The importance of the major risk and protective factors for cervical cancer in women by age group was evaluated with the use of data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. This study included 416 cervical cancer cases and 20,985 referents confirmed as free of cancer. Cases and referents were divided into three age groups: the younger, middle and older age groups (30-44, 45-54 and 55-69 years old, respectively). Logistic model was applied separately to the three groups to estimate odds ratios (ORs) of smoking, beverage and dietary habits with adjustment for marital and reproductive factors. The elevated OR of current smokers was observed consistently in all age groups, while alcohol intake did not show any increased ORs. Dietary control for health lowered ORs for all three age groups, and the effect appeared to be more pronounced among the older age group (OR = 0.49, 95% confidence interval: 0.30-0.80). Higher frequency intake of green-yellow vegetables consistently afforded lower ORs among all three age groups. This risk increment of smoking and risk reduction by dietary control were consistent in all age groups. These findings suggested practicable prevention strategy for the cervical cancer by modifying general life style.

In Japan the incidence of cervical cancer has been high, but has recently been decreasing gradually, while the incidence of endometrial cancer is running at lower levels but is gradually increasing. To clarify the common and/or specific risk and/or protective factors of cervical cancer(CC) in contrast with endometrial cancer (EC), a comparative case-control study was conducted at the Aichi Cancer Center Hospital, Japan. In total, 556 CC cases and 145 EC cases were included and 26,751 women, confirmed as free of cancer, were chosen as the common control group. Odds ratio and its 95% confidence interval (95%CI) for each exposure variable were estimated by using an unconditional logistic regression model adjusted for age and first-visit year. Habitual smoking and experience of pregnancy increased the risk of CC, while decreasing the risk of EC. Greater body mass index (>20), daily intake of fruit and more frequent intake of boiled or broiled fish (>1-2 times/week) decreased the risk of CC, whereas they increased the risk of EC. Daily intake of milk decreased the risk of CC. The results obtained from this study suggest that several EC-increasing risk factors are in fact CC-decreasing determinants. The observed risk reduction in both CC and EC by physical exercise and dietary control for health is noteworthy from the public health standpoint and warrants further investigation.

Background: An association of human leukocyte antigen (HLA)-DQw3 alleles with squamous cell carcinoma (SCC) of the cervix has been reported in some European populations, but the significance of HLA-DQw3 has not been examined in other populations to the authors' knowledge. The interaction between HLA-DQw3 and human papillomavirus (HPV) in SCC remains to be clarified., Methods: To elucidate the association of HLA-DQ alleles with SCC of the cervix, DNA samples extracted from blood lymphocytes of 23 patients with SCC were amplified by the polymerase chain reaction (PCR) using specific primers for the DQB1 genes, and then, each HLA-DQB1 genotype was defined by digestion with restriction enzymes. Human papillomavirus typing also was performed in all cases by PCR, using specific primers for the E6 regions of cancer-associated HPV types (HPV 16, 18 and 33)., Results: Twenty patients (87%) carried a DQB1 gene-encoding HLA-DQw3, compared with 49.4% Japanese control subjects in the International Histocompatibility Workshop panel (P = 0.0003). Human papillomavirus 16 or HPV 18 DNA was detected in 86% of the patients. In 13 of the patients with invasive carcinoma with HPV, a high incidence of not only HLA-DQw3 but also of HLA-DQw1 was observed compared with that in control subjects (P = 0.0019, P = 0.047, respectively). The correlation between DQB1*03 alleles and HPV infection was not statistically significant., Conclusion: The frequency of HLA-DQw3 alleles was higher in the authors' patient group than in the control group, suggesting that the HLA-DQw3 molecules may influence the development of SCC of the cervix in young Japanese women. In the patients with HPV-positive invasive carcinoma, the association with HLA-DQw1 molecules suggested that it also may influence the progression of SCC.

OK-432, a streptococcal preparation, was administered to patients with stage Ib and II cervical carcinoma except for adeno- and adenosquamous carcinomas. To evaluate the efficacy of OK-432 precisely, 177 patients were stratified by clinical stage, radiotherapy, and lymph node metastasis after complete radical hysterectomy and pelvic lymphadenectomy. Within each stratum, patients were divided randomly into OK-432 and control groups. 85 patients received OK-432 and 92 patients did not. No significant difference was observed in overall 5-year disease free rates between the OK-432 and the control groups, although the mean diameter of erythema on SU-polysaccharide (SU-PS) skin test was larger in the OK-432 group than in the control group. In stage IIb, a significant difference was observed between the OK-432 and control groups. This difference, however, could be attributed in part to the different incidence of the lymph node metastasis. In stage II without lymph node metastasis, 5-year disease free rate was significantly higher in the OK-432 group.

Poly(ADP-ribose) synthetase activity in human cervical cancer cell nuclei was found to be approximately twice that of normal cervical cell nuclei. Using antipoly(ADP-ribose) antibody, frozen section of normal tissue were stained by indirect-immunofluorescence and it was demonstrated that the fluorescence of nuclei in squamous cells decreased during maturation. Correspondingly, superficial cells appearing in smear specimens had less nuclear fluorescence compared with parabasal cells in the same smear. However, cancer cells in cervical smears had marked nuclear fluorescence using immunostaining and were easily distinguished from normal cells.