Pretreatment levels of serum squamous cell carcinoma antigen and urine polyamines in women with squamous cell carcinoma of the cervix.

OBJECTIVES: To investigate whether pretreatment levels of serum squamous cell carcinoma antigen (SCCA) and urine polyamines can predict lymph node metastases in patients with early stage cervical carcinoma. METHODS: Pretreatment measurement of serum SCCA and urine polyamine levels was carried out for 419 women. Of those women, 104 with stage IB and IIA cancer received radical surgery and had tumor size reassessed postoperatively. RESULTS: The women had increased levels of serum SCCA (>2.0 ng/mL) and elevated urine polyamines (>45 micromol/g of creatinine) with advanced cancer stage (P<0.01). The median SCCA level was significantly higher in women with metastatic disease than that in those without lymph node involvement (3.9 vs. 1.1; P<0.01). Women with nodal involvement also had significantly higher median levels of urine polyamines than those without nodal disease. CONCLUSIONS: Pretreatment measurement of SCCA and urine polyamine levels may help in predicting lymph node metastases in women with early stage cervical carcinoma.     

血清SCCAg及CA125在诊断宫颈鳞癌及评价预后中作用的研究

目的:探讨血清SCCAg及CA125用于宫颈鳞癌诊断、手术治疗及预后的价值。方法:选取ⅠA2～ⅡA期宫颈鳞状细胞癌为研究组,20例CIN及20例慢性宫颈炎分别为对照组1和对照组2。采用固相夹心法酶联免疫吸附实验(ELISA)检测血清SCCAg的数值,采用化学发光免疫分析法(CLIA)检测血清CA125数值。比较分析血清SCCAg及CA125与宫颈鳞癌临床病理特征、手术疗效及预后的关系。结果:宫颈鳞癌组术前血清SCCAg及CA125水平均高于慢性宫颈炎组,差异均具有统计学意义(P<0.01)。宫颈鳞癌组术前SCCAg水平高于CIN组,差异有统计学意义(P<0.001);宫颈鳞癌组术前CA125水平与CIN组的差异无统计学意义(P=0.049,P>0.0167)。血清SCCAg、CA125诊断宫颈鳞癌的临界值分别为1.03ng/ml、8.16U/ml。血清SCCAg、CA125及两项联合诊断宫颈癌的ROC曲线下面积分别为0.954、0.718、0.960,两项联合后诊断性能无明显增加。宫颈鳞癌术前血清SCCAg随临床分期增加具有线性增加的趋势。脉管有否癌栓、盆腔淋巴结有否转移也与术前血清SCCA水平有关,差异有统计学意义(P=0.011,P=0.043)。宫颈鳞癌组手术治疗后的血清SCCAg及CA125水平均有逐渐降低趋势,差异有统计学意义(P均<0.001)。结论:血清SCCAg对宫颈鳞癌有较高的诊断价值,可考虑作为诊断及手术疗效评估指标之一,有助于初步判断脉管及盆腔淋巴结转移。血清CA125对于宫颈鳞癌诊断、手术评估及随访的价值均低于SCCAg,与SCCAg联合不能增加诊断的敏感度和特异度。     

The clinical values of squamous cell carcinoma antigen and carcinoembryonic antigen in patients with cervical cancer treated with concurrent chemoradiotherapy

The objective of this study was to determine the prognostic significance of the pre- and posttreatment serum levels of the squamous cell carcinoma antigen (SCC-Ag) and carcinoembryonic antigen (CEA). From 2001 to 2005, 211 patients were treated with concurrent chemoradiotherapy (CCRT). The SCC-Ag and CEA levels were measured before treatment, 1 month after treatment, and during the follow-up. The association between the pretreatment tumor marker levels and the clinical prognostic factors was evaluated. The frequency of complete remission (CR) and the normalization of the posttreatment tumor marker were also analyzed. The pretreatment serum levels of CEA and SCC-Ag were elevated in 68 (32.2%) and 148 (70.1%) patients, respectively. The number of patients with an elevated pretreatment SCC-Ag level was associated with the FIGO stage, tumor volume, and pelvic lymph node status. The pretreatment CEA was only significantly related to the tumor volume and pelvic lymph node involvement. One month after completing CCRT, the CEA and SCC-Ag levels were normalized in almost all patients with an incidence of 88.2% (60/68) and 93.2% (138/148), respectively. Among the patients who gained CR with a previously elevated pretreatment CEA and SCC-Ag, the values were normalized in 92.1% (58/63) and 96.4% (134/139) at 1 month, respectively. Combination assays of the pre- and posttreatment serum CEA and SCC-Ag levels appear to be useful for both predicting the prognosis and estimating the clinical response in cervical cancer. However, the routine combined measurement with SCC-Ag of CEA in all patients had limited additional effect in predicting the prognostic significance.     

Post-treatment serial serum squamous cell carcinoma antigen (SCC) in the monitoring of squamous cell carcinoma of the cervix

Serum squamous cell carcinoma antigen (SCC) was raised in 62% of 308 patients with squamous cell carcinoma of the cervix before treatment. Post-treatment SCC levels were raised in 69 patients (22.4%). Retrospective review showed that persistently raised SCC level after treatment was significantly associated with persistent or recurrent disease in squamous cell carcinoma of the cervix. The specificity of persistently raised SCC level in association with recurrent disease was 98.2%. The sensitivity in association with recurrent disease was 74.7%. The positive predictive values was 94.2%. The median lead time for recurrence was 4 months. SCC was raised in 38% of patients with clinical evidence of disease in the vagina. One patient had raised SCC one month prior to clinical detection of vaginal metastasis and was salvaged by an exenterative procedure. SCC was raised in 71–91% of patients with metastatic disease in the lung, lymph nodes or other distant sites. Thus, persistently raised SCC level after treatment of squamous cell carcinoma should alert the clinician to look for recurrent disease especially in distant metastatic sites. Post-treatment raised SCC level was associated with less than 5% 5-year survival rate whereas in patients with normal SCC level, the 5-year survival rate was 87%.     

Raised serum squamous cell carcinoma antigen levels in malignant transformation of mature cystic ovarian teratoma

Mature cystic ovarian teratoma with malignant transformation to squamous cell carcinoma was diagnosed in four patients. Squamous cell carcinoma (SCC) antigen serum levels were elevated at diagnosis and during progression of the disease, but normal in complete remission. Elevated serum SCC antigen levels were also found in four out of 19 patients with mature cystic teratoma of the ovary. Cystic fluid from mature cystic teratoma could contain very high levels of the SCC antigen (> 1000 µg l⁻¹) without any sign of malignant transformation.     

宫颈癌患者淋巴结HPV16/18感染及血清鳞状细胞癌抗原检测的临床意义

目的:探讨宫颈癌患者淋巴结HPV16/18感染及术前血清鳞状细胞癌抗原(SCCA)水平与临床病理参数的相关性,以及宫颈分泌物及淋巴结中HPV16/18感染和术前血清SCCA水平三者之间的关系。方法:采用实时荧光定量PCR法检测35例宫颈癌患者的宫颈分泌物及淋巴结HPV16/18阳性率,同时用ELISA法检测术前血清SCCA水平。结果:宫颈癌患者宫颈分泌物及淋巴结HPV16/18阳性率分别为80%(28/35)和20%(7/35)。7例组织学阳性淋巴结及28例阴性淋巴结HPV16/18阳性率分别为85.71%(6/7)和3.57%(1/28)。SCCA阳性率为37.14%(13/35)。淋巴结HPV16/18阳性感染与术前SCCA水平相关(r=0.650,P0.01),两者均与淋巴结转移、间质浸润深度及脉管累及有关(P0.05),而和宫颈分泌物HPV16/18阳性感染无关(P0.05)。结论:HPV16/18在组织学阳性淋巴结中感染率高,与宫颈癌患者淋巴结转移密切相关。而阴性淋巴结中的HPV16/18检出提示微转移。术前SCCA水平与淋巴结转移相关。     

Use of squamous cell carcinoma antigen as a biomarker of chemotherapy response in patients with metastatic cervical carcinoma

Objective

To examine the use of squamous cell carcinoma antigen (SCCA) as a biomarker of chemotherapy response in patients who underwent chemotherapy for metastatic cervical carcinoma.

Study design

The study population consisted of patients who underwent first-line chemotherapy for metastatic cervical carcinoma between 1999 and 2009. SCCA levels were serially measured before, during and after chemotherapy. Radiographic responses were evaluated according to the criteria of the World Health Organization. A logistic model was used to determine the best prediction model, and internal and external validation of the prediction model were performed to compare the areas under the receiver operating characteristic curves (AUCs).

Results

In total, 55 patients were included in the analysis. Data for 32 patients enrolled in various clinical trials were used to develop the prediction model. Patients who achieved a radiographic response showed a significant decline in SCCA levels between the second and third cycles of chemotherapy, whereas patients who did not achieve a radiographic response showed constant SCCA levels over the same period. The prediction model was developed on the basis of changes in the SCCA level between the second and third cycles of chemotherapy (AUC = 0.832) and the baseline SCCA level. The AUC after external validation, calculated using the data of the clinical practice population (n = 22), was 0.871.

Conclusions

A response to chemotherapy was possible for patients in whom SCCA levels declined between the second and third cycles of chemotherapy.     

The role of pretreatment squamous cell carcinoma antigen level in locally advanced squamous cell carcinoma of the uterine cervix treated by radiotherapy

The purpose of this study was to determine the pretreatment serum squamous cell carcinoma antigen (SCC-ag) level as a generally applicable measurement in predicting and estimating the treatment outcome of patients with locally advanced SCC of the cervix. Three hundred fifty-two patients with stage IIB-IVA SCC of the cervix were managed with both external irradiation and high-dose rate intracavitary brachytherapy. A significantly higher median SCC-ag was seen in association with increasing stage, tumor size, and lymph node involvement. The difference in disease-free survival (DFS) between stages IIB and III patients was not statistically significant with SCC-ag level <2 ng/mL. In multivariate analysis, median SCC-ag level (> or =6.0 ng/mL) and lymph node metastases had significant independent effects on absolute survival and DFS. A direct linear relationship (y=-2.932x+ 84.896) existed between the median SCC-ag of groups distributed by pretreatment prognostic factors and the 5-year DFS rate. The 5-year DFS rate as a function of SCC-ag level defined by cervix size, lymph node status, and hydronephrosis was obtained from a formula combining risk scores and the baseline survival function. From the obtained formulas, we can objectively estimate the treatment outcome in patients with locally advanced squamous cell cervical cancer.     

Simultaneous diagnosis and therapy of invasive cervical carcinoma and invasive vulvar carcinoma. A case report

Invasive squamous cell carcinoma of the vulva is predominantly a disease of postmenopausal woman with a mean age of approximately 65 years. After treatment for cervical cancer patients have an increased risk of developing second squamous cell malignancy of the lower genital tract. This study reports the case of a patient with double malignancy—invasive cervical cancer and invasive vulvar cancer. She underwent radical hysterectomy, bilateral adnexectomy and pelvic bilateral lymphadenectomy and at the same time radical vulvectomy and bilateral inguinal lymphadenectomy. After surgery she was referred to radiotherapy. The postoperative course was uneventful and at 14 months of follow-up, the patient showed no evidence of recurrence.     

Smoking cessation counseling in women with genital intraepithelial neoplasia

Objective

Cigarette smoking is a risk factor for cervical, vaginal, vulvar, and anal dysplasia. We will study the prevalence of cigarette smoking in patients with genital dysplasia and effect of counseling on smoking cessation.

Methods

All patients with genital dysplasia were screened for smoking history. One clinician provided smoking cessation counseling using the US Department of Health 5 A's technique: ask patients about their smoking status, advise smokers to quit, assess their readiness to quit, assist with their smoking cessation effort, and arrange for follow-up visits. Patients were informed on how smoking may cause worsening of genital dysplasia and increased risk of progression to cancer. Each patient received 2 counseling sessions, but no pharmacological or psychological interventions. Smoking cessation was evaluated by patient self-report via phone or during clinic visits.

Results

From January 2007 to December 2010, 344 patients were referred to our gynecologic oncology clinic for evaluation of genital dysplasia. Patients who were smokers (n = 125, 36%) were counseled to cease smoking in 2 counseling sessions, with 100% compliance for attendance. At study analysis (July 2011), 83 patients still smoke and 40 patients quit smoking (smoking cessation rate of 32%). Caucasian patients (P = .0013) and patients with vulvar dyplasia (P = .411) seemed to smoke more than other races and patients with cervical/vaginal dysplasia respectively.

Conclusion

Smoking cessation counseling for the genital dysplasia patients who smoked was associated with smoking cessation in 32% of the patients.     

A comparative analysis of human papillomavirus types 16 and 18 and expression of p53 gene and Ki-67 in cervical,vaginal, and vulvar carcinomas

This study aimed to investigate the correlation between HPV positivity, p53 overexpression, and cell proliferative activity in cervical, vaginal, and vulvar squamous cell carcinoma. METHODS: Sixteen vaginal and 31 vulvar squamous cell carcinomas were examined retrospectively for overexpression of p53 gene and Ki67 antigen by immunohistochemistry and for the presence of HPV types 16 and 18 DNA using a polymerase chain reaction (PCR) method. The results were compared with those obtained from 40 cervical squamous cell carcinomas. RESULTS: HPV type 16 or 18 DNA was detected in 21 (52.8%) of 40 cases of cervical carcinomas and p53 overexpression in one (2.5%), while HPV DNA sequences were detected in seven (43.7%) of 16 cases of vaginal carcinoma and p53 overexpression in three (18.7%). With regard to vulvar carcinoma, HPV was harbored in four (12.8%) of 31 cases and p53 overexpression in 19 (61.2%). These results indicated statistically significant inverse correlations between HPV positivity and p53 overexpression (R = -0.999, P < 0.0001). Overexpression of Ki-67 was detected in 28 (70.0%) of 40, 12 (75.0%) of 16, and 21 (67.7%) of 31, cervical, vaginal, and vulvar carcinomas, respectively. There was no significant difference among the three groups. CONCLUSIONS: In cervical carcinoma, HPV types 16 and 18 might play a common causal role, and in vulvar carcinoma, p53 gene mutations might be a main causal factor for carcinogenesis. Vaginal carcinoma, on the other hand, is considered to have transitional characteristics between cervical and vulvar carcinoma.     

Serum squamous cell carcinoma antigen levels in patients with invasive squamous vulvar and vaginal cancer: a preliminary report

Pretreatment serum squamous cell carcinoma antigen (SCC) levels were obtained in 12 patients with invasive vulvar and 5 patients with invasive vaginal squamous cancer. Only 4 of 12 (33%) patients with vulvar cancer and 1 of 5 (20%) patients with vaginal cancer, usually those with more advanced disease, had elevated serum SCC levels at the time of diagnosis.     

Bleomycin-mitomycin C in advanced squamous cell carcinoma of the female genital tract

Bleomycin and mitomycin C have been reported to be active against advanced squamous cell carcinoma of the uterine cervix. Miyamoto et al reported a total response rate of 93% and complete response in 80% of the first 15 patients treated by sequential combination of bleomycin and mitomycin C. Updated results by Miyamoto reveal an 88.3% total response rate with a 65.3% complete response. However, others have reported poor results using the protocol outlined by Miyamoto. Using this protocol, 11 patients with advanced squamous cell carcinoma were treated at the authors' institution. There were no complete responses: one patient with partial response (9%), four with stable disease (36%), and six (55%) with progressive disease.     

Expression of indoleamine 2,3-dioxygenase predicts shorter survival in patients with vulvar squamous cell carcinoma (vSCC) not influencing on the recruitment of FOXP3-expressing regulatory T cells in cancer nests

Objective

Regulatory T cells (Tregs), and the enzyme indoleamine 2,3-dioxygenase (IDO), have potential regulatory properties for immune escape in cancer. Inhibitors of IDO are available and could potentially be used in vulvar cancer if IDO was proved to drive progression of the disease. The aim of this study was to evaluate the expression of factor forkhead boxP3 (FOXP3), a marker of Tregs, and IDO in vulvar squamous cell carcinoma (vSCC), and to verify their prognostic significance.

Methods

76 primary tumors and 35 lymph node metastases derived from 76 patients with full clinical history were analyzed. The intratumoral infiltration of Tregs and IDO expression within cancer were evaluated by immunohistochemistry.

Results

The number of Tregs in primary tumor and in corresponding lymph node metastasis was significantly correlated. Intensity of Treg infiltrates in the primary and metastatic sites was not correlated to IDO expression and had no influence on the overall patient survival. High IDO expression was associated with significantly worse overall survival among vSCC patients and was found to be an independent prognostic factor similarly to the tumor grade and patient's age.

Conclusions

The degree of intratumoral Treg infiltrates is an individual feature and remains stable throughout the course of the disease without impact on the patient's survival. IDO expression predicts shorter survival of vSCC patients. If immunologic tolerance of the tumor is promoted by the overexpression of IDO it will not influence the number of intratumoral Tregs. IDO expression seems to be an independent prognostic factor in patients with vSCC.     

Squamous cell carcinoma antigen serum levels as prognostic parameter in patients with early stage vulvar cancer

OBJECTIVE: To determine whether SCC-Ag serum levels can be used as a prognostic parameter in surgically treated early stage vulvar cancer. METHODS: SCC-Ag serum levels were measured preoperatively in 61 surgically staged patients with squamous cell vulvar cancer (UICC pT1 and pT2). Results were correlated to clinical data. RESULTS: Mean (standard deviation) SCC-Ag serum levels in patients with vulvar cancer were 1.5 (1.99) ng/mL. SCC-Ag serum levels were significantly higher in patients with pT2 vulvar cancer (2.2 [2.6] ng/mL) compared with patients with pT1 vulvar cancer (1.0 [1.2] ng/mL, P = 0.034). SCC-Ag serum levels were not associated with lymph node involvement (P = 0.1), tumor grade (P = 0.6), and patients' age (P = 0.5). Multivariate Cox regression models considering tumor stage, lymph node involvement, patients' age, and SCC-Ag serum levels as covariates showed that lymph node involvement (P = 0.04 and P = 0.01) and tumor stage (P = 0.006 and P = 0.009), but not SCC-Ag serum levels (P = 0.8 and P = 0.6), and patients' age (P = 0.08 and P = 0.22) are prognostic factors for disease-free and overall survival, respectively. CONCLUSION: SCC-Ag serum levels cannot be used as an additional prognostic parameter in patients with surgically treated early stage vulvar cancer.     

Increased expression level of squamous cell carcinoma antigen 2 and 1 ratio is associated with poor prognosis in early-stage uterine cervical cancer

Squamous cell carcinoma antigen (SCCA) is a tumor marker for patients with squamous cell carcinoma of uterine cervix, lung, and esophagus. It was encoded by two highly homologous genes, SCCA1 and SCCA2. However, the relevance of SCCA genes to squamous cell carcinogenesis and patient outcome remains far from clear. In this study, by using laser microdissection and real-time quantitative polymerase chain reaction procedures, the messenger RNA (mRNA) expression of the SCCA1 and SCCA2 genes in normal, dysplastic, and malignant squamous epithelia from uterine cervical tissues were analyzed and correlated with outcome of cancer patients. We found that the SCCA2/A1 mRNA ratios were progressively increased from normal, dysplastic, to cancer cells, and the mean ratio was significantly higher in cancer tissues than that in normal epithelium (P= 0.02). The SCCA2/A1 mRNA ratios were not significantly associated with types of human papillomavirus infection (P > 0.05). High SCCA2/SCCA1 mRNA ratios (ratio >1) were an independent predictor of disease recurrence (relative risk: 3.58; P= 0.003). Of the 38 patients with cervical cancer, 12 patients with high SCCA2/SCCA1 mRNA ratios had a significant lower 2-year disease-free survival of only 50%, while it was 92% in those with low SCCA2/SCCA1 mRNA ratios (P < 0.001). In conclusion, our study indicated that the ratios of SCCA2 to SCCA1 RNA were increased during the process of cervical carcinogenesis, and patients with elevated SCCA2/A1 ratio carried a higher risk for recurrence in early-stage uterine cervical cancer.     

Clinical significance of combined use of macrophage colony-stimulating factor and squamous cell carcinoma antigen as a selective diagnostic marker for squamous cell carcinoma arising in mature cystic teratoma of the ovary

OBJECTIVES: Mature cystic teratoma of the ovary transforms into malignant tumors, mostly squamous cell carcinomas, at an incidence of approximately 2%. Preoperative diagnosis of squamous cell carcinoma arising in mature cystic teratoma of the ovary is a difficult task. The present study aims to assess whether combined use of two serum tumor markers, macrophage colony-stimulating factor (M-CSF) and squamous cell carcinoma antigen (SCC), is effective in preoperatively diagnosing squamous cell carcinoma arising in mature cystic teratoma of the ovary, distinguishing it from mature cystic teratoma without malignant transformation. METHODS: Serum levels of M-CSF and SCC were assayed using blood samples collected preoperatively from 31 patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary and 133 patients with mature cystic teratoma of the ovary without malignant transformation. RESULTS: In 22 of the 31 (71.0%) patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary, the serum M-CSF levels exceeded the upper limit of the normal level (1056 U/ml). This positive incidence of the elevated serum M-CSF levels was significantly higher compared with that (13.5%, 18/133) observed in patients with benign cystic teratoma of the ovary (P < 0.0001). Regarding the serum levels of SCC, 13 of 31 (41.9%) patients with malignant tumors showed positive values exceeding the cutoff value of 2.0 ng/ml. Again, this incidence of positive cases was significantly higher compared with that (15.0%, 20/133) observed in patients with benign tumors (P < 0.01). There was no correlation between the serum levels of M-CSF and SCC among patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary. Patients with malignant tumors testing positive for elevated M-CSF did not necessarily test positive for SCC. Patients with positive values for excess M-CSF and/or SCC constituted 87.1% of the total (27/31). Even when patients were restricted to those with stage I tumors, a value as high as 83.3% (15/18) was still obtained for those testing positive for elevated M-CSF and/or SCC. CONCLUSION: Serum M-CSF was proven to be useful as a tumor marker for detecting squamous cell carcinoma arising in mature cystic teratoma of the ovary. Combined use of serum M-CSF and SCC as a marker seemed to be useful in the selective diagnosis of mature cystic teratoma of the ovary harboring malignant squamous carcinoma, discriminating it from that without malignant carcinoma.     

Second lower genital tract squamous cell carcinoma following cervical cancer. A clinical study of 46 patients

BACKGROUND: Patients after treatment for cervical cancer have increased risk of developing second squamous cell malignancy of the lower genital tract. MATERIAL AND METHODS: A retrospective study of 46 patients with second lower genital tract epidermoid cancers following previous treatment for invasive cervical carcinoma. RESULTS: Patient age at diagnosis of cervical cancer was 27 to 68 years (median 44 years) and at diagnosis of the second malignancy - 43 to 72 years (median 63 years). There were four cases (9%) of synchronous cancers. Time span between metachronous malignancies ranged from 66 to 406 months (median 206 months). In 32 cases (70%) second lesion was located in the vagina and in 14 (30%) - in the vulva. Out of 35 previously irradiated patients, in 24 (69%) second tumor was located within the high dose volume and in 11 (31%) - outside it. Treatment of second cancer consisted of surgery in 12 patients (26%), radiotherapy in 23 (50%), combined surgery and radiotherapy--in five (11%), chemotherapy in four (9%) and surgery plus chemotherapy - in one case. Median survival was 52 months and five-year survival from the diagnosis of second malignancy - 47.5%. No prognostic factors for survival were identified. CONCLUSION: Treatment outcome in patients with second lower genital tract carcinoma is unsatisfactory due to poor feasibility of another definite treatment after previous radical surgery and/or radiotherapy.