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。     

HPV DNA Presence and HPV Genotypes as Prognostic Factors in Low-Stage Squamous Cell Cervical Cancer

Sixty-four patients with FIGO stages IB and IIA squamous cell carcinoma of the uterine cervix were studied to assess the prognostic potential of the presence of HPV DNA and HPV genotypes in the tumor, as detected by a general primer-mediated polymerase chain reaction followed by a type-specific PCR on paraffin-embedded tissue sections of the primary tumor. The prevalence of various HPV types in 32 patients with positive lymph nodes was compared to the prevalence found in 32 age-matched controls with negative lymph nodes. In both patient groups HPV DNA was found in all cases. The prevalence rates of HPV types 16, 18, and X in the positive and negative lymph node group were 78% versus 72%, 13% versus 9%, and 3% versus 16%, respectively. These differences were not statistically significant. HPV genotypes 6, 11, and 31 were not found. Differences in recurrence rate and 5-year survival rate between the patient groups with different tumor-containing HPV genotypes were not statistically significant. Nor was there any statistically significant relationship between HPV type and other well-know prognosticators. In conclusion, in our study a 100% HPV DNA prevalence was found in squamous cell cervical carcinomas. Neither the presence of HPV DNA nor the HPV genotype appeared to be related to either the presence of lymph node metastases at the time of initial treatment or to 5-year survival.     

HPV status in sentinel nodes might be a prognostic factor in cervical cancer

OBJECTIVE: Although there have been studies that focused on the correlation between the HPV presence of pelvic lymph nodes and pathological metastasis in patients with cervical cancer, the biologic role of HPV DNA in lymph nodes still remains uncertain. We performed this study to investigate the correlation between the sentinel-node HPV status and pelvic lymph node metastasis in patients with cervical cancer. The patients were followed up for 3 years to evaluate the clinical role of HPV in sentinel nodes as a prognostic factor. METHODS: From August 2001 to July 2003, 57 patients affected by stages IB-IIA cervical cancer had sentinel-node biopsies performed during radical hysterectomy and pelvic and paraaortic lymphadenectomy. Each detected sentinel node was divided into two parts. One part of them was submitted for frozen section examination and the other was submitted for HPV typing by oligonucleotide microarray. After follow-up, we analyzed the outcome of the patients with respect to the influence of sentinel-node HPV. RESULTS: Sentinel nodes were identified in all patients. A total of 79 nodes from 57 patients were detected as sentinel nodes. Metastasis in the sentinel nodes were found in 10 patients (17.6%) by frozen section and 11 patients by pathologic examination. The results of sentinel lymph node frozen biopsy were statistically significant for predicting the metastasis of the pelvic lymph nodes (P<0.05), but showed one false-negative case. HPV DNA was detected in the cervical cancer lesions of 55 patients (96.5%) and 80.0% (44/55) of them were found to have HPV DNA in the sentinel nodes as well. HPV DNA was detected in sentinel nodes of 10 patients among 11 patients with lymph node metastasis. Disease recurred in five patients and one of them did not show pelvic lymph node metastasis at surgery. But, all of these patients had HPV in sentinel nodes. The combination of sentinel-node frozen biopsy and HPV typing showed a negative predictive value of 100% in predicting non-metastasis of lymph node and no recurrence of disease. CONCLUSION: Our results suggested the possibility that sentinel-node HPV typing could play a supportive role to reduce the false-negative rate of the sentinel-node biopsy. All of five patients with recurrence had HPV infection in the sentinel nodes. Absence of HPV in sentinel nodes showed reliable negative predictive value for lymph node metastasis and recurrence. Additional study will be needed to confirm the clinical application of the sentinel-node procedure and to determine whether there is a correlation of HPV status of sentinel nodes to lymph node metastasis and recurrence in cervical cancer patients.     

Invasive cervical cancer in young women. Clinicopathologic correlation and demonstration of human papillomavirus by in situ hybridization.

It has been suggested that invasive cervical carcinoma is biologically more aggressive in young patients than in older patients. The clinicopathologic characteristics and human papillomavirus (HPV) status of women < or = 35 years of age with invasive cervical carcinoma treated at Emory University Hospital from 1985-1989, were evaluated in a retrospective study. The group consisted of 23 patients, 35% of all patients with invasive cervical carcinoma. Age at diagnosis, clinical stage, histologic classification, lymph node status, treatment and clinical follow-up were obtained from medical records. HPV status was evaluated by colorimetric in situ hybridization for HPV types 6, 11, 16, 18, 31, 33 and 35 in archival formalin-fixed paraffin-embedded tumor material available from 16 of the patients. This study found that the young patients had lower survival and greater extent of disease than predicted by clinical staging. The rate of detection of HPV (69% positive) and HPV typing (type 16 predominated) in these young patients showed no difference from other series of cervical carcinomas from all age groups. Although a higher proportion of patients who died of disease had HPV-negative tumors (3/7, 43%) than those patients who were alive and free of disease (2/9, 22%), this difference was not statistically significant (P = .73, Fisher's Exact T-Test).     

Prognostic significance of high-risk HPV status in advanced cervical cancers and pelvic lymph nodes

OBJECTIVE: In this study, we investigated the presence of high-risk (HR) HPV types most prevalent in the Hungarian population in surgically removed cervical cancers and pelvic lymph nodes. The aim of our work was to determine the prognostic significance of HPV status in the lymph nodes draining the tumor. METHODS: Primary tumor specimens from 150 patients and 900 lymph node samples (six per case) were studied. Fifty-six/150 were early (FIGO IA-IB) stage, while 94/150 were advanced (FIGO IIA-IIIB) stage cancers. Beside histopathological evaluation, DNA extracted from the tissue samples was subjected to nested PCR to detect characteristic type-specific sequences of HPVs 16, 18 and 33. Moreover, clinicopathological data were collected for an average 48-month postoperative follow-up period for the purposes of statistical analysis. RESULTS: The presence of HR-HPV types in the lymph nodes shows no correlation with disease-free survival, whereas the presence of lymph node metastases significantly decreases life expectancy (P = 0.002). Lymph nodes with metastases more frequently carry HR-HPV than nodes with no evidence of tumorous infiltration (65% versus 36%, P < 0.001); however, a high number of metastases surrounding HR-HPV-positive tumors were found negative for the viruses (42/120). CONCLUSIONS: HR-HPV status of pelvic lymph nodes draining cervical cancers has no noticeable influence on the life expectancy of the patients. HR-HPV-positive tumor cells do not necessarily have a selective advantage in forming metastases. Presumably, a number of alterations in cellular genes rather than the presence of papillomavirus DNA may have a decisive role in the progression of cervical cancers.     

Modified radical hysterectomy in the treatment of early squamous cervical cancer

OBJECTIVE: The aim of this study was to evaluate the results of modified radical hysterectomy in the treatment of early cervical cancer. MATERIAL AND METHODS: A retrospective chart review of 56 patients with stage I (IA in 35, IB in 21) squamous cervical carcinoma treated with modified radical hysterectomy and followed for a minimum of 5 years (mean, 12 years; range, 5.1-29) was conducted. All pathology slides were reviewed for tumor size, grade, depth of invasion, and lymph-vascular permeation. RESULTS: The mean depth of invasion was 0.5 cm (range, 0.1-2.5 cm), and the mean tumor size was 1.1 cm (range, 0.1-7 cm). Only 3 patients (5.4%) had positive nodes. None of the patients with tumors 2 cm or less in size had positive nodes, whereas 33.3% of the patients with tumors more than 2 cm in size had positive nodes. A recurrence developed in 2 patients (5-year recurrence rate of 3.6%). There were 10 deaths during the entire follow-up period, but only 2 were related to cervical cancer. The disease-specific and overall 5-year survival rates were 96.4 and 94.6%, respectively. The disease-specific 5-year survival rate was 100% among the 47 patients with tumors 2 cm or less and 75% for the 9 patients with tumors larger than 2 cm. Univariate analysis identified stage, lymph node status, and tumor size as statistically significant prognostic factors for overall survival. Tumor grade, lymph-vascular permeation, and depth of invasion (1-3 mm vs >3 mm) were not statistically significant for overall survival. CONCLUSIONS: Modified radical hysterectomy appears to be effective surgical therapy for patients with squamous cervical carcinoma 2 cm or less in size.     

Human papillomavirus genotype as a prognostic indicator in carcinoma of the uterine cervix

The clinical implications of specific human papillomavirus (HPV) types in invasive cervical carcinomas are only beginning to be appreciated. In this series of 100 women with cervical cancers analyzed for the presence of HPVs 6, 11, 16, 18, and 31 by Southern blot hybridization, a more aggressive clinical behavior was demonstrated for tumors containing HPV 18 than for those with HPV 16 or those in which no HPV was identified. Among 69 stage Ib tumors, no significant differences were found in the size of tumor, presence of parametrial involvement, or lymph node metastasis among patients whose tumor contained HPV 16, HPV 18, or no HPV DNA; however, 45% of the women with HPV 18-containing tumors (five of 11) had recurrence, as compared with only 16% of those with HPV 16 (five of 31) during the 20-month mean follow-up period. This tendency for HPV 18-containing tumors to recur was seen with all histologic subtypes of cervical cancers and with all grades of tumor. In addition, patients with HPV 18-containing tumors were more likely to give a history of recent normal Papanicolaou smears than were those whose tumors contained HPV 16. Forty-four percent of women with HPV 18 in their tumors had a history of three class I Papanicolaou smears in the 3 years before the diagnosis of cancer, whereas a similar history was elicited in only 16% of those with HPV 16 in their tumors, suggesting that HPV 18-containing tumors might progress to invasion without a prolonged preinvasive period.     

Human papillomavirus (HPV) DNA in primary cervical cancer and in cancer free pelvic lymph nodes--correlation with clinico-pathological parameters and prognostic significance

OBJECTIVE: To assess whether the presence of human papilloma virus (HPV) DNA and/or several genotypes of HPV DNA in primary cervical cancer and cancer free pelvic lymph nodes are correlated with several clinicopathological parameters of well-defined prognostic significance and whether virological parameters are predictors of long-term survival in cancer patients. PATIENTS AND METHODS: 223 cases of cervical cancer patients included in this retrospective study underwent follow-up evaluation. Survival and cause of death were examined for 204 (91.4%) patients, with a mean follow-up time of 4.4 years. HPV DNA was detected using the high sensitive polymerase chain reaction (PCR) method followed by HPV DNA sequencing for HPV genotyping. These results were correlated with well-defined clinicopathological parameters and survival data. RESULTS: HPV DNA was detected by PCR in 150 of 203 (73.4%) tissue specimens of cervical cancer patients. DNA sequence analysis revealed the presence of HPV 16 (n = 68, 45.3%), HPV 18 (n = 49, 32.6%) and rare HPV types (n = 33, 22.1%). HPV genotypes correlated significantly with histological tumor types, node status, blood vessel invasion and lymph space involvement. The presence of HPV DNA in cervical cancer as well as the genotype of HPV 16 could also be confirmed as significant prognostic factors in the univariate Cox Regression Analysis (RR 2.856, p < 0.003 resp. RR 3.444, p < 0.0001). The presence of HPV DNA in cancer free pelvic lymph nodes was significantly correlated to the concomitant manifestation of pelvic lymph node metastases (RR 3.1, p < 0.0001). In the multivariate analysis, however, HPV DNA in primary tumor and in negative pelvic lymph nodes failed to be of prognostic relevance. Exclusively, HPV 16 appears to impact independently on the overall survival in cervical cancer patients (RR 3.653, p < 0.002). CONCLUSION: The detection of HPV 16 genotype may play an important adjunct role in assessing prognosis of cervical cancer patients. The clinical impact of the presence of HPV DNA in primary tumors and cancer free pelvic lymph nodes remains to be investigated in further studies. The exact mechanisms by which HPV influence the prognosis of cervical cancer patients have to be defined.     

Evaluation of the scalene lymph nodes in primary and recurrent cervical carcinoma

Open biopsy of the left scalene lymph nodes has been utilized to identify distant spread of cervical carcinoma in selected groups of patients who do not have other clinical evidence of disseminated disease. Twenty-one patients with primary cervical carcinoma and histologically proven para-aortic lymph node metastases and 10 patients with centrally recurrent tumors underwent scalene lymph node biopsy at Walter Reed Army Medical Center or the Naval Hospital, Bethesda, Maryland, between July 1, 1979 and June 30, 1985. All patients undergoing scalene node biopsy had clinically negative physical examinations. There were no surgical complications. All 31 biopsies were negative for metastatic tumor. Combined with previously reported data from this institution, 3 of 28 patients (11%) with primary cervical carcinoma and involved para-aortic nodes, and 6 of 35 patients (17%) with centrally recurrent disease had subclinical scalene node metastases. Patients with clinically suspicious scalene lymphadenopathy had fine needle aspiration cytology performed to document metastatic disease. The success of this technique has eliminated the need for open biopsy in these patients. Scalene node biopsy provides valuable prognostic information in patients with cervical cancer who have positive para-aortic lymph nodes. It also obviates surgical exploration in some patients felt to have resectable recurrent disease who actually have subclinical distant spread.     

宫颈癌盆腔淋巴结微转移分子检测及其意义

目的:研究宫颈癌患者盆腔淋巴结人乳头状瘤病毒(HPV)和端粒酶活性的表达及其临床意义。方法:应用FQ-PCR和PCR-ELISA方法检测61例Ia~IIb期宫颈癌组织和盆腔淋巴结HPV载量和端粒酶活性表达,并与常规病理结果比较。同时取15例良性疾病患者的淋巴结作为阴性对照组;分析宫颈癌淋巴结转移与各种病理因素的关系。结果:宫颈癌淋巴结HPV16/18和端粒酶阳性率显著高于常规病理阳性率(P<0.01),对照组淋巴结HPV16/18和端粒酶均为阴性。常规病理阳性的淋巴结HPV16/18拷贝数和端粒酶活性高于病理阴性的淋巴结,但低于原发灶,差异有统计学意义。淋巴结HPV16/18和端粒酶表达呈显著正相关(r=0.60,P<0.01)。临床分期晚和癌灶浸润深的患者易发生淋巴结转移。结论:与常规病理相比,采用FQ-PCR和PCR-ELISA技术检测HPV和端粒酶活性表达能显著提高宫颈癌淋巴结微转移的检出率。     

Parametrial spread of cervical cancer in patients with negative pelvic lymph nodes.

OBJECTIVE: We studied the incidence and prognostic implications of parametrial involvement according to tumor volume in a series of cervical cancer patients with negative pelvic lymph nodes. METHODS: We reviewed a series of 351 node-negative patients with stage IB, IIA, or IIB cervical cancer treated with class III radical hysterectomy. The surgical specimens were processed as step-serial giant sections and tumor volume was calculated. Overall, 180 patients had tumors <5 mL, 120 had tumors of 5-20 mL, and 51 had tumors >20 mL. Parametrial involvement was classified as continuous, discontinuous, or involvement of blood vessels or lymph nodes and according to location as medial or lateral. A total of 302 patients had squamous cell tumors and 49 had adenocarcinomas. The mean duration of follow-up was 9.3 years. RESULTS: Overall, 44 of 351 patients (12.5%) had parametrial involvement. The rate of parametrial involvement in patients with tumors <5, 5-20, and >20 mL was 6.7, 12.5, and 33%, respectively. Isolated involvement of the medial parametrium increased with tumor size (3.8, 8.3, and 27.5%, respectively), whereas isolated involvement of the lateral parametrium was seen in 2.2, 1.6, and 0% of the cases. Involvement of both the medial and the lateral portions of the parametrium was seen in 0.5, 2.5, and 5.9% of the specimens, respectively. There were no differences in the rate of parametrial involvement between squamous cell carcinomas and adenocarcinomas. The 5-year disease-free survival rates in patients without or with parametrial involvement were 90.2% vs 90%, 91.7% vs 92.9%, and 84.7% vs 67%, respectively. CONCLUSION: The lateral portion of the parametrium can be involved in patients with cervical cancer and negative pelvic lymph nodes, but this is uncommon. In this series of patients treated with type III radical hysterectomy, parametrial involvement had no influence on disease-free survival.     

Presence of Oncogenic HPV DNAs in Cervical Carcinoma Tissues and Pelvic Lymph Nodes Associating with Proliferating Cell Nuclear Antigen Expression

The presence of oncogenic HPV DNAs (HPV-16/18) in cervical carcinomas and their normal and metastatic pelvic lymph nodes and the expression patterns of proliferating cell nuclear antigen (PCNA) in cervical carcinomas were retrospectively studied to elucidate the possible roles of them in malignant transformation and progression of the disease. HPV-16/18 DNAs were detected by polymerase chain reaction using HPV E6 type-specific primers in 79 patients with cervical cancer: 31 patients who had pelvic lymph node metastasis (group I) and 48 patients without pelvic lymph node metastasis (group II) who were proven by pathologic examination of surgical specimens. HPV-16 or -18 DNAs were detectable in cervical carcinoma tissues in 60 patients from 79 cervical cancer patients (75.9%; HPV-16 was 67.1% and HPV-18 was 8.9%). HPV DNAs were amplified from metastatic pelvic lymph nodes in 13 patients of group I (42%) and from nonmetastatic lymph nodes in 7 group I patients (22.5%). Recurrence was identified in 9 group I patients (29.0%) in 3 years of follow-up. HPV DNAs were amplified from nonmetastatic lymph nodes in 11 group II patients (22.9%). Two group II patients, who had HPV-16 DNA by PCR in nonmetastatic nodes, were recurrent. PCNA was overexpressed in 66.7% of HPV-16- or -18-positive cervical cancers and 16.7% of HPV-16- or -18-negative cervical cancers. However, the expression levels of PCNA in cervical cancers were not influenced by the presence of oncogenic HPV DNA or pathologic metastasis in the pelvic lymph nodes. In conclusion, HPV DNA could be amplified from some metastatic and nonmetastatic pelvic lymph nodes and the detectability of oncogenic HPV DNA in pelvic lymph nodes may represent the poor outcome in the treatment of disease. The expression of PCNA protein which was associated with presence of oncogenic HPV DNAs in cervical cancers, suggesting activation of S phase of cell cycle, may contribute to the malignant progression by HPV-16 or -18.     

Intraoperative lymphatic mapping in cervix cancer patients undergoing radical hysterectomy: A pilot study

OBJECTIVE: Intraoperative lymphatic mapping and sentinel lymph node identification (SLN) have been increasingly evaluated in the treatment of a variety of solid tumors, particularly breast cancer and melanoma. We sought to evaluate the feasibility of these procedures in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. METHODS: Twenty patients with normal-appearing lymph nodes underwent intracervical injection of isosulfan blue dye (lymphazurin 1%) at the time of planned radical hysterectomy and bilateral pelvic/low paraortic lymphadenectomy (40 nodal basins). Regional lymphatic tissue was inspected for dye uptake into lymphatic channels and lymph nodes. Tumor characteristics, surgical findings, and specific locations of lymphatic dye uptake were recorded and correlated with final pathology results. RESULTS: Sentinel lymph nodes were identified in 12 of 20 (60%) patients. A total of 23 sentinel nodes were identified in 17 of 40 (43%) nodal basins dissected (range: 0-2 per basin). Successful SLN identification was less likely in patients with tumors >4 cm compared with those with tumors 相似文献   

Poor clinical outcome in early stage cervical cancer with human papillomavirus-18 positive lymph nodes

Epidemiologic and molecular studies have proven that human papillomavirus (HPV) plays an important role in the development of cervical cancer. However, the role of the virus in the progression of the disease, i.e. in the development of lymph node metastasis and in the adverse clinical outcome is poorly understood. We have been using the polymerase chain reaction (PCR) to study the presence and typing of human papillomavirus DNA since 1980 in cervical cancers and pelvic lymph nodes from the same patients. Out of the series of 47 cervical cancer patients we focused on four women (age: 41, 33, 35 and 56 years) in this article. The follow-up of these patients revealed early recurrences of the disease (7, 7, 17, 22 months) with very short survival (9, 10, 21, 24 months). Although we detected HPV-18 positivity both in the cervical tumors and in the regional lymph nodes too in all four cases, lymph nodes were negative by routine hystology in case of the three young patients (21, 33, 35 years of age). Our observations suggest that HPV type 18 positive cervical cancer patients, despite negative histological findings in the lymph nodes should be consider as a subpopulation for poor outcome especially in the young age group (p=0,022, Fisher's exact test).     

Prognostic significance of lymph node variables and human papillomavirus DNA in invasive vulvar carcinoma

OBJECTIVE: The present study investigates the influence of lymph node pathological features and HPV DNA status on the prognosis of vulvar invasive tumors. METHODS: This study includes 184 consecutive cases of primary invasive squamous cell carcinoma of the vulva treated by radical surgery from 1975 to 1992, in S?o Paulo, Brazil. Clinical follow-up data was collected from patient files and hematoxilin-eosin sections were reviewed. HPV detection and typing was done by polymerase chain reaction (PCR), using specific and generic primers, followed by dot blot hybridization (DBH) with type-specific oligonucleotide probes for 19 HPV types. Age-adjusted Kaplan-Meier survival curves and Cox proportional hazards models were used to analyze the cancer risk associations for all DNA and pathology-related variables. RESULTS: Among 161 cases tested by PCR, 38 (23.6%) were positive for high-risk HPV types. Regional lymph nodes of 43 cases, including all those of HPV-positive tumors and a sample of the ones removed from patients with HPV negative tumors, were evaluated by the same method. HPV DNA was found in the lymph nodes of 10 cases. In every case, at least one lymph node was metastatic and the HPV detected in the lymph nodes were of the same type as those found in the primary tumor in all cases. Multivariate analysis including age, race, pattern of invasion, tumor thickness, inflammatory reaction, surgical margins, number of node metastases, presence of extracapsular growth, depth of invasion, and presence of high-risk HPV DNA was performed. Following automated selections of this model, node variables important for prognosis that remained were number of node metastases and presence of extracapsular growth. CONCLUSIONS: Patients with four or more node metastases associated with extracapsular spread were 5.6 (95%CI: 2.3-13.1) times more likely to die from cancer and 10.0 (95%CI: 4.0-24.9) times more likely to have a recurrence than patients without metastases. The HPV status in the tumor was not important as a prognostic factor.     

Predictive value of HPV DNA in lymph nodes in surgically treated cervical carcinoma patients--a prospective study

OBJECTIVE: High-risk types of HPV are etiological factors in cervical cancer. Lymph node involvement in cervical cancer patients reduces 5-year survival rates by 25-60%. However, the influence on survival of HPV DNA positivity in histopathologically negative lymph nodes remains unresolved. METHODS: The study included 116 of 148 patients who underwent Piver type III radical hysterectomy and pelvic lymphadenectomy and who showed HPV DNA positivity in the primary lesion. Lymph node tissues were tested for the presence of HPV DNA, using a PCR technique. RESULTS: We found the presence of HPV DNA sequences in lymph nodes dissected intraoperatively in 81 (69.83%) cases. In analysis, we compared patients from 3 groups: HPV- and metastatic-negative (LN HPV-M-); HPV-positive metastatic-negative (LN HPV+M-); and metastatic-positive (LN M+). We discovered that survival in groups LN M+ and LN HPV+M- did not differ statistically (p=0.37). However, the survival periods in these two groups differed when compared with LN HPV-M- patients (p<0.001). Using Cox's proportional hazards model, we found that the presence of lymph node HPV DNA, and FIGO stage, and primary lesion volume were independent parameters correlating with survival and mortality risk. CONCLUSION: We conclude that the presence of HPV DNA in lymph nodes is an early sign of metastasis and should be treated as such in prognostic outlook and planning the therapeutic strategy.     

Effect of neoadjuvant chemotherapy on locally advanced cervical cancer by internal iliac arterial infusion

<正>Objective:To evaluate the effect of preoperative chemotherapy on locally advanced cervical cancer by internal iliac arterial infusion.Methods:Sixty two patients with bulky or locally advanced cervical cancer from 1999 to 2004 were underwent internal iliac arte- rial infusion chemotherapy by using Seldinger technique.Combined regimens were applied in- cluding cisplatin as the major drug.Two weeks later,all patients received radical hysterectomy. Results:The local tumor regression rate was 93.55%.Postoperative pathologic examination showed that no cervical tumor residue in stumps were found in 61 of 62 patients who underwent radical hysterectomy.Large quantity of necrotic tissue appeared on primary tumor.In 16 patients with positive lymph nodes,15 demonstrated necrotic lymph nodes.Conclusion:Internal iliac ar- terial infusion chemotherapy could effectively reduce tumor volume,increase surgical success rate and decrease lymph nodes and subclinical metastasis rates.     

18F-FDG positron-emission-tomography in cervical carcinoma: preliminary findings

18F-Fluorodesoxyglucose-Positron-Emission-Tomography (18F-FDG-PET) is a novel imaging modality for malignancies. This study was initiated to define the efficiency of PET in detecting and characterizing metabolically the primaries and in preoperatively assessing of lymphonodal metastases of cervical cancer. 15 patients with histologically proven cervical carcinoma were studied with 18F-FDG-PET regarding 18F-FDG-uptake of primary tumor and evidence as well as extent of lymphonodal metastases. 18F-FDG-PET and histopathological results were compared after radical hysterectomy with pelvic and supplementary in 7 cases paraaortal lymphadenectomy. All primary tumours showed 18F-FDG accumulation and had a mean maximal standardized uptake value (SUV) of 8.0 +/- 5.3. 3/6 lymph node metastases were obtained with 18F-FDG-PET. Micrometastases (size of metastasis < or = 0.2 cm) were present in 2 patients with false negative PET results. Regarding the subgroup with paraaortal lymph node dissection, PET detected one patient with metastases, the other one had micrometastasis, while metastasis was not observed by PET. The accuracy of PET is 73% for assessment of pelvic lymph nodes and 86% for assessment of paraaortal lymph nodes. In conclusion 18F-FDG accumulates reliably in primaries of cervical cancer. Regarding assessment of lymph node metastases PET seems to be of potential use, offering metabolic information independent of the size of metastatic lymph nodes. An improvement of accuracy can be expected if combined evaluation of morphologic and metabolic images is performed.     

Multivariate analysis of histopathologic prognostic factors for invasive cervical cancer treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy

BACKGROUND: The aim of this study was to identify the independent histopathologic prognostic factors for patients with cervical carcinoma treated with radical hysterectomy including paraaortic lymphadenectomy. METHODS: A total of 187 patients with stage IB to IIB cervical carcinomas treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy were retrospectively analyzed. The median follow-up period was 83 months. Cox regression analysis was used to select independent prognostic factors. RESULTS: Using multivariate Cox regression analysis, lymph node (LN) status (negative vs. metastasis to pelvic nodes except for common iliac nodes vs. common iliac/paraaortic node metastasis), histopathologic parametrial invasion, lymph-vascular space invasion (LVSI), and histology of pure adenocarcinoma were found to be independently related to patients' poor survival. For patients who had a tumor histologically confined to the uterus and have neither parametrial invasion nor lymph node metastasis, LVSI was the most important prognostic factor, and histologic type, depth of cervical stromal invasion, and tumor size were not related to survival. The survival of patients with a tumor extending to parametrium or pelvic lymph node(s) was adversely affected by histology of pure adenocarcinoma. When the tumor extended to common iliac or paraaortic nodes, patients' survival became quite poor irrespective of LVSI or histologic type of pure adenocarcinoma. Patients' prognosis could be stratified into low risk (patients with a tumor confined to the uterus not associated with LVSI: n = 80), intermediate risk (patients with a tumor confined to the uterus associated with positive LVSI, and patients with squamous/adenosquamous carcinoma associated with pelvic lymph node metastasis or parametrial invasion: n = 86), and high risk (patients with pure adenocarcinoma associated with pelvic lymph node metastasis or parametrial invasion, and patients with common iliac/paraaortic node metastasis: n = 21) with an estimated 5-year survival rate of 100 +/- 0 (mean +/- SE)%, 85.5 +/- 3.9%, and 25.1 +/- 9.7%, respectively. CONCLUSIONS: LN status, parametrial invasion, LVSI, and histology of pure adenocarcinoma are important histopathologic prognostic factors of cervical carcinoma treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy. Prognosis for patients with cervical carcinoma may be stratified by combined analysis of these histopathologic prognostic factors. Postoperative therapy needs to be individualized according to these prognostic factors and validated for its efficacy using randomized clinical trials.     

Histopathological prognostic factors in primary surgically treated cervix carcinoma]

OBJECTIVE: Standardised morphologic evaluation of radical hysterectomy specimens in primary surgically treated cervical cancer improves the selection of cases for adjuvant therapy and the precision for prognosis and may be helpful in quality control of oncologic surgery. MATERIAL AND METHODS: Following standardised macroscopic evaluation [29] the original histologic slides of all surgically treated patients with cervical cancer were searched for tumor type, histologically proven pelvic lymph node metastases (PLM), lympho-vascular space involvement (LVSI), tumor differentiation (grading), peritumoral inflammatory response, pattern of cervical wall involvement and relative depth of invasion. The results were compared with follow up. RESULTS: The frequency of patients up to 35th year of age was 28.8% and increased between 1979 and 1993 of about 10% (p > 0.05). Younger women represented more pT1 b1-tumors (55.6% vs. 47%), but without statistic significance. Contrary to advanced tumor stage and the presence of PLM, adenocarcinomatous histology (5.1% of all cases) was not associated with poor prognosis. Patients with pT1b-tumors of more than 4 cm largest extension (pT1 b2) showed a twice-fold frequency of PLM and pelvic recurrences. Five-year survival rate (5-Y-SR) decreased (82.7% vs. 64.9%) and more patients died of cancer (p = 0.005, each). Diffuse infiltration pattern was accompanied with higher rate of tumor recurrency and a shortening of 5-Y-SR compared with pushing borders at the front of infiltration, 38% versus 13.7% and 45.4% versus 75.2%, respectively. Similar was seen in poorly differentiated tumors (G3), compared with well differentiated (G1) carcinomas (recurrency: 15.1% vs. 27.5%, 5-Y-SR 75.7% vs. 59.3%; p < 0.05). Cases with the presence of LVSI, absence of peritumoral inflammatory response and deep cervical infiltration (> 66%) were accompanied with poor prognostic outcome. CONCLUSIONS: In patients with primary surgically treated cervical cancer prognostic risk evaluation can be made by standardised histopathologic handling of hysterectomy specimens. Cases with early cervical cancer and high tumor load (pT1 b2), advanced staged disease (pT2 b), histologically proven PLM, LVSI, poor tumor differentiation (G3), absence of peritumoral inflammatory response and deep cervical wall infiltration are associated with poor prognostic outcome. Patients with these morphologic patterns, which can be established by clinical examination and diagnostic biopsy, represent the clientel for adjuvant or neoadjuvant therapy.