Surgical staging for endometrial cancer in the elderly - is there a role for lymphadenectomy?

Objectives

We sought to evaluate the effect of systematic lymphadenectomy (LND) on endometrial cancer-specific survival in an elderly population.

Methods

Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program from 1988 to 2006. Women who underwent primary hysterectomy for non-serous, non-clear cell endometrial carcinoma were included. Women were stratified by age (< 70, 70-79, and ≥ 80) and disease-specific survival (DSS) was analyzed via the Kaplan-Meier method and stratified by postoperative grade. Cohorts were compared using the log-rank test. In a simulated population, the disease-specific survival of women with pre-operative grade 1 endometrial carcinoma was calculated using a weighted average survival accounting for those upgraded at final pathology.

Results

Endometrial cancer was identified in 5759 women ≥ 80 years old. Disease specific survival at 5 years for the LND and no LND groups was 93.4% and 94.5% (p = 0.36) for grade 1, 84.4% and 85% (p = 0.97) for grade 2, and 65.9% and 60.9% (p = 0.002) for grade 3. In the simulated pre-operative grade 1 group, 5 year disease-specific survival (DSS) was 91% in the LND group and 92% in the no LND group.

Conclusion

In women older than 80, systematic lymphadenectomy is associated with improved DSS for high grade, but similar DSS for low grade endometrial cancer, consistent with what is seen with younger women. As there is no clear survival benefit to lymphadenectomy in elderly women presenting with low grade disease, the surgeon should carefully weigh the surgical risks and benefits in this patient population, which may be at higher risk for morbidity.     

Location of aortic node metastases in locally advanced cervical cancer

Background

To assess the location of aortic node metastasis in patients with locally advanced cervical cancer undergoing extraperitoneal aortic lymphadenectomy to define the extent of the aortic lymphadenectomy.

Material and methods

Between August 2001 and December 2010, 100 consecutive patients with primary locally advanced cervical cancer underwent extraperitoneal laparoscopic aortic and common iliac lymphadenectomy. The location of aortic node metastases, inframesenteric or infrarenal was noted.

Results

The mean number ± standard deviation (SD) of aortic nodes removed was 15.9 ± 7.8 (range 4-62). The mean number ± SD of inframesenteric (including common iliac) nodes removed was 8.8 ± 4.5 (range 2-41) and the mean number ± SD of infrarenal nodes removed was 7.8 ± 4.1 (range 2-21). Positive aortic nodes were observed in 16 patients, and in 5 (31.2%) of them the infrarenal nodes were the only nodes involved, with negative inframesenteric nodes.

Conclusion

Inframesenteric aortic nodes are negative in the presence of positive infrarenal nodes in about one third of patients with locally advanced cervical cancer and aortic metastases.     

Clinical and pathologic features of young endometrial cancer patients with loss of mismatch repair expression

Objective

This study examines premenopausal and early menopause patients in a unique population with endometrial cancer and loss of mismatch repair (MMR) gene expression. The purpose is to compare clinical and pathologic differences in patients with loss of expression (LOE) to those with normal expression (NE).

Methods

Endometrial cancer patients under age 60 in-between 1998 and 2008 were identified from a single tumor registry. Clinical and pathologic data were abstracted from records. Staining for expression of MSH6, MSH2, MLH1, and PMS2 were performed on archived tissue blocks. Statistical analysis was performed.

Results

158 patients were analyzed; 58% Asian, 34% Pacific Islander, and 8% Caucasian. 31 demonstrated LOE of at least one MMR gene; 127 retained NE. 50% Caucasian, 21.9% Asian, and 12.5% Pacific Island populations had LOE of one or more MMR genes. LOE was found to have a higher incidence of Grade III (p = 0.0013) and stage 3-4 tumors (p = 0.0079), mean depth of myometrial invasion (p = 0.0019), lymphovascular space invasion (p = 0.0020), nodal metastases (p = 0.0157), and a lower incidence of Grade I (p = 0.0020) and stage 1A tumors (p = 0.0085). LOE had a significantly lower mean BMI (p = 0.0001). 35% of patients in the NE vs zero in the LOE group had a BMI greater than 40.

Conclusion

Younger patients with LOE endometrial cancer appear to represent a clinically significant subgroup of patients without features characteristically found in classic type 1 endometrial cancer generally demonstrating lower BMI and tumors associated with poor prognostic characteristics. It is unclear if the distinctive ethnicity found in Hawaii has a significant impact on outcome. Further investigation is necessary to identify appropriate treatment strategies.     

20 year experience of postoperative radiotherapy in IB-IIA cervical cancer patients with intermediate risk factors: impact of treatment period and concurrent chemotherapy

Objective

To compare the long-term clinical outcomes of adjuvant radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT) in cervical cancer patients with intermediate risk factors.

Methods

Between 1990 and 2010, 110 cervical cancer patients with 2 or more intermediate risk factors (deep stromal invasion, lymphovascular space invasion, and large tumor size) underwent adjuvant RT (n = 56) or CCRT (n = 54) following radical surgery. Because CCRT had been performed since 2000, patients were divided into 3 groups regarding treatment period and the addition of chemotherapy, RT 1990-1999 (n = 39), RT 2000-2010 (n = 17) and CCRT 2000-2010 (n = 54). Majority of concurrent chemotherapeutic regimens were carboplatin and paclitaxel (n = 48).

Results

Five-year relapse-free survival (RFS) rates for RT 1990-1999, RT 2000-2010 and CCRT 2000-2010 were 83.5%, 85.6% and 93.8%, respectively. CCRT 2000-2010 had a significant decrease in pelvic recurrence (p = 0.012) and distant metastasis (p = 0.027). There were no significant differences in overall survival and RFS between RT 1990-1999 and RT 2000-2010. Acute grade 3 and 4 hematologic toxicities were more frequently observed in CCRT 2000-2010 (p < 0.001). However, acute grade 3 and 4 gastrointestinal (GI) and chronic toxicities did not differ between the groups.

Conclusions

This study shows that the addition of concurrent chemotherapy to postoperative RT in cervical cancer patients with intermediate risk factors may improve RFS without increasing acute GI and chronic toxicities, although hematologic toxicities increased significantly.     

Relevance of gamma-glutamyltransferase--a marker for apoptotic balance--in predicting tumor stage and prognosis in cervical cancer

Introduction

Recent large epidemiologic population-based studies identified gamma-glutamyltransferase (GGT) as a marker for increased cervical cancer incidence. Furthermore, high levels of GGT seem to increase the risk of progression of high-grade cervical dysplasia to invasive carcinoma. Therefore, we evaluated the association between pre-therapeutic serum GGT levels, tumor stage and prognosis in patients with cervical cancer.

Materials and methods

In this multi-center trial, pre-therapeutic GGT levels were examined in 692 patients with cervical cancer. GGT levels were correlated with clinico-pathological parameters. Patients were assigned to previously described GGT risk groups and uni- and multivariable survival analyses were performed.

Results

GGT serum levels were associated with FIGO stage (p < 0.0001) and age (r = 0.2, p < 0.0001) but not with lymph node involvement (p = 0.85), and histological type (p = 0.98). High-risk GGT group affiliation (p = 0.01 and p < 0.0001) was associated with poor disease-free and overall survival in a univariate analysis, but not in a multivariable Cox-regression model (p = 0.59 and p = 0.171). We further investigated the association between prognosis and GGT and observed a linear correlation between GGT and prognosis. Therefore we were not able to identify a clear prognostic cut-off value for GGT in patients with cervical cancer.

Conclusions

High GGT - a marker for apoptosis and cervical cancer risk - is associated with advanced tumor stage in patients with cervical cancer.     

Tubal ligation frequency in Oklahoma women with cervical cancer

Objective

Infrequent Pap screening is an important risk factor for cervical cancer. We studied the association between contraceptive methods, screening frequency, and cancer.

Methods

Women (n = 2004) enrolled in the cross-sectional Study to Understand Cervical Cancer Endpoints and Determinants (SUCCEED) underwent colposcopy to evaluate an abnormal Pap test. Questionnaire data were compared between those with cervical intraepithelial neoplasia (CIN) 3/adenocarcinoma in situ (AIS) and those with invasive cancer to identify factors associated with cancer. Logistic regression was used to calculate age-stratified measures of association between contraceptive method and Pap frequency as well as tubal ligation (TL) and cancer risk.

Results

In all age groups, women with TL were more likely to have had no Pap screening in the previous 5 years compared to women using other contraception: 26-35 years (OR 4.6, 95% CI 2.4-8.6; p < 0.001), 36-45 years (OR 3.8, 95% CI 2.1-7.0; p < 0.001), and 46-55 years (OR 2.2, 95% CI 1.0-4.9; p = 0.050). Subjects with cancer (n = 163) were more likely to have had a TL (41% vs. 21%, p < 0.001) than those with CIN 3/AIS (n = 370). Age-stratified analyses showed increased odds of tubal ligation in women with cancer versus those with CIN 3/AIS between 25 and 45 years, with a significant increase in women 26 to 35 years old (OR 3.3, 95% CI 1.4-8.1; p = 0.009). Adjusting for Pap frequency changed the effect only slightly, suggesting that increased risk was not fully mediated by lack of screening.

Conclusion

Contraceptive type is associated with Pap screening. Women with TLs obtain less frequent Pap testing and may be at an increased risk for cervical cancer.     

Cytology versus visual inspection with acetic acid among women treated previously with cryotherapy in a low-resource setting

Objective

To compare visual inspection with acetic acid (VIA) with conventional cervical cytology as a follow-up cervical cancer screening method in women who had been treated previously with cryotherapy.

Methods

Salvadoran women screened with VIA and treated with cryotherapy within 3 years were eligible to participate. Study participants were rescreened with VIA, Pap smear, colposcopy, 4-quandrant biopsy, and endocervical curettage.

Results

Of 147 women enrolled in the study, post-cryotherapy VIA was positive in 39 women (26.5%; 95% CI, 19.6%-34.4%). Of these 39, 1 woman had CIN 1 or higher on biopsy. Post-cryotherapy Pap smear was positive (ASCUS or higher) in 6 women (4.1%; 95% CI, 1.5%-8.7%). Of these 6, 2 women had CIN 1 or higher on biopsy. Post-cryotherapy specificity was significantly higher for Pap compared with VIA (95.8% [138/144]; 95% CI, 91.2%-98.5% vs 73.6% [106/144]; 95% CI, 65.6%-80.6%; P < 0.001).

Conclusion

As the single-visit approach for cervical cancer screening gains popularity, more women will have been treated with cryotherapy. Appropriate follow-up screening is therefore vital. Cytology may be a more suitable screening method than VIA in low-resource settings for women treated previously with cryotherapy.     

The significance of perineural invasion in early-stage cervical cancer

Introduction

Cervical cancer spreads directly and through lymphatic and vascular channels. Perineural invasion is an alternative method of spread. Several risk factors portend poor prognosis and inform management decisions regarding adjuvant therapy.

Objective

To evaluate the incidence and significance of PNI in early cervical cancer.

Methods

Retrospective chart review of early-stage cervical cancer patients (IA-IIA) from 1994 to 2009.

Results

One hundred ninety two patients were included, 24 with perineural invasion in the cervical stroma (cases) and 168 without (controls). The mean age of the cases was 53 years, versus 45.9 in the controls (P = 0.01). PNI was associated with more adjuvant therapy (P = 0.0001), a higher stage (P = 0.005), a larger tumor size (≥ 4 cm) (P < 0.0001), lymphovascular space invasion (P = 0.002), parametrial invasion (P < 0.0001) and more tumor extension to the uterus (P = 0.015). On multivariate analysis using an adjusted hazard ratio, risk factors for recurrence included grade (HR, 95% CI; 3.61, 1.38-9.41) and histopathology (HR, 95% CI; 2.85, 100-8.09). Similarly, risk factors for death included grade (HR, 95% CI; 3.43, 1.24-9.49) and histopathology (HR, 95% CI; 3.71, 1.03-13.33). Perineural invasion was not identified as an independent risk factor for either recurrence or death. The mean follow up time was 56 months. There was no significant difference in recurrence (P = 0.601) or over-all survival (P = 0.529) between cases and controls.

Conclusion

While perineural invasion was found to be associated with multiple high-risk factors, it was not found to be associated with a worse prognosis in early cervical cancer.     

Comparative effectiveness of minimally invasive and abdominal radical hysterectomy for cervical cancer

Objective

We analyzed the uptake, morbidity, and cost of laparoscopic and robotic radical hysterectomies for cervical cancer.

Methods

We identified women recorded in the Perspective database with cervical cancer who underwent radical hysterectomy (abdominal, laparoscopic, robotic) from 2006 to 2010. The associations between patient, surgeon, and hospital characteristic and use of minimally invasive hysterectomy as well as complications and cost were estimated using multivariable logistic regression models.

Results

We identified 1894 patients including 1610 (85.0%) who underwent abdominal, 217 (11.5%) who underwent laparoscopic, and 67 (3.5%) who underwent robotic radical hysterectomy were analyzed. In 2006, 98% of the procedures were abdominal and 2% laparoscopic; by 2010 abdominal radical hysterectomy decreased to 67%, while laparoscopic increased to 23% and robotic radical hysterectomy was performed in 10% of women (p < 0.0001). Patients treated at large hospitals were more likely to undergo a minimally invasive procedure (OR = 4.80; 95% CI, 1.28-18.01) while those with more medical comorbidities (OR = 0.60; 95% CI, 0.41-0.87) were less likely to undergo a minimally invasive surgery. Perioperative complications were noted in 15.8% of patients who underwent abdominal surgery, 9.2% who underwent laparoscopy, and 13.4% who had a robotic procedure (p = 0.04). Both laparoscopic and robotic radical hysterectomies were associated with lower transfusion requirements and shorter hospital stays than abdominal hysterectomy (p < 0.05). Median costs were $9618 for abdominal, $11,774 for laparoscopic, and $10,176 for robotic radical hysterectomy (p < 0.0001).

Conclusion

Uptake of minimally invasive radical hysterectomy for cervical cancer has been slow. Both laparoscopic and robotic radical hysterectomies are associated with favorable morbidity profiles.     

Metabolic risk factors and cervical cancer in the metabolic syndrome and cancer project (Me-Can)

Background

Little is known about the association between metabolic risk factors and cervical cancer carcinogenesis.

Material and methods

During mean follow-up of 11 years of the Me-Can cohort (N = 288,834) 425 invasive cervical cancer cases were diagnosed. Hazard ratios (HRs) were estimated by the use of Cox proportional hazards regression models for quintiles and standardized z-scores (with a mean of 0 and a SD of 1) of BMI, blood pressure, glucose, cholesterol, triglycerides and MetS score. Risk estimates were corrected for random error in the measurements.

Results

BMI (per 1SD increment) was associated with 12%, increase of cervical cancer risk, blood pressure with 25% and triglycerides with 39%, respectively. In models including all metabolic factors, the associations for blood pressure and triglycerides persisted. The metabolic syndrome (MetS) score was associated with 26% increased corrected risk of cervical cancer. Triglycerides were stronger associated with squamous cell carcinoma (HR 1.48; 95% CI, 1.20-1.83) than with adenocarcinoma (0.92, 0.54-1.56). Among older women cholesterol (50-70 years 1.34; 1.00-1.81), triglycerides (50-70 years 1.49, 1.03-2.16 and ≥ 70 years 1.54, 1.09-2.19) and glucose (≥ 70 years 1.87, 1.13-3.11) were associated with increased cervical cancer risk.

Conclusion

The presence of obesity, elevated blood pressure and triglycerides were associated with increased risk of cervical cancer.     

Keratosis reduces sensitivity of anal cytology in detecting anal intraepithelial neoplasia

Objective

To identify factors that may contribute to poor sensitivity of anal cytology in contrast to the sensitivity of anoscopy in heterosexual women.

Methods

We analyzed 324 patients with biopsy confirmed diagnosis of genital intraepithelial neoplasia (either vulva, vaginal, or cervical) from 2006 to 2011 who underwent both anal cytology and anoscopy. Cytology, anoscopy, and biopsy results were recorded. Biopsy specimens underwent independent analysis for quality of specimen. Also, biopsy specimens were analyzed for characteristics that may contribute to correlation, or lack thereof, between anal cytology and anoscopic directed biopsy.

Results

133 (41%) patients had abnormal anoscopy and underwent directed biopsy. 120 patients with normal anal cytology had anoscopy directed biopsies, resulting in 58 cases of AIN (sensitivity 9.4%; 0.039-0.199). This cohort was noted to have extensive keratosis covering the entire dysplastic anal lesion. 18 patients yielded abnormal anal cytology. Of these patients, 13 had anoscopic directed biopsies revealing 6 with AIN and absent keratosis (specificity 88.6%; 0.78-0.95). The κ statistic for anal cytology and anoscopy was − 0.0213 (95% CI = − 0.128-0.086).

Conclusion

Keratosis reduces the sensitivity of anal cytology. Furthermore, anal cytology poorly correlates with anoscopy in the detection of AIN (κ statistic = − 0.0213).     

Overexpression of gelsolin in human cervical carcinoma and its clinicopathological significance

Objectives.

Cervical carcinoma is the second most common cause of death from gynecological cancers worldwide. Knowledge of the molecular mechanisms underlying the tumorigenesis of cervical cancer cell, except human papilloma virus infection, is limited.

Methods.

A microarray was used to study the differential expression of genes in cancerous tissues to identify new molecular markers for diagnosis and prognosis. Their differential expression was confirmed with Western blotting and immunohistochemical analyses. The clinical correlations and prognostic significance of the aberrantly expressed proteins were evaluated to identify novel biomarkers of cervical cancer.

Results.

The expression of gelsolin was significantly upregulated in 78% of patients with cervical cancer, and gelsolin was selected for further study. Gelsolin expression was stronger in cervical tumor tissues than in the surrounding noncancerous tissues (P < 0.001). Gelsolin expression in the plasma of cervical cancer patients was increased 2.2-fold compared with that of healthy control subjects (P < 0.001). The levels of plasma gelsolin in the early and late stages were significantly different (P = 0.006). According to immunohistochemical analysis, increased gelsolin expression was associated with histological type and FIGO stage II. The 5-year overall survival and recurrence-free survival rates for the low-expression group (cut-off = 115) were significantly higher than those of the high-expression group. Cancer cells with reduced gelsolin expression exhibited reduced migration and proliferation.

Conclusions.

These results provide strong evidence that gelsolin plays an important role in cellular proliferation and migration in cervical cancer and suggest that gelsolin is a promising marker for cervical cancer screening and prognosis.     

Prevalence and genotype distribution of human papillomavirus in women with cervical cancer or high-grade precancerous lesions in Chengdu, western China

Objective

To study the prevalence and genotype distribution of human papillomavirus (HPV) among women with cervical cancer or high-grade squamous intraepithelial lesions (HSIL) in western China.

Methods

Cervical cast-off cells from 144 women with cervical cancer and 63 women with HSIL were tested for HPV genotypes using an oligonucleotide microarray.

Results

The overall HPV prevalence was 80.6% in cases of carcinoma and 61.9% in cases of HSIL. The most common genotypes were HPV-16 (carcinoma, 68.1%; HSIL, 34.9%) and HPV-58 (carcinoma, 8.3%; HSIL, 17.5%). Other high-risk types included HPV-18, -31, -33, -35, -45, and -52, with HPV-18 more common in adenocarcinomas than in squamous cell carcinomas (21.4% vs 3.1%; P < 0.02). The HPV prevalence was lower among patients older than 49 years (P < 0.02).

Conclusion

The prevalence of HPV-16 and HPV-58 was high. This finding may help to improve HPV vaccination and cervical cancer prevention programs in western China.     

Prognostic significance of adenocarcinoma histology in women with cervical cancer

Objectives

We performed a population-based analysis to determine the effect of histology on survival for women with invasive cervical cancer.

Methods

The Surveillance, Epidemiology and End Results database was used to identify women with stage IB-IVB cervical cancer treated from 1988 to 2005. Patients were stratified by histology (squamous, adenocarcinoma, and adenosquamous). Clinical characteristics, patterns of care, and outcomes were analyzed using multivariable logistic regression and Cox proportional hazards models.

Results

A total of 24,562 patients were identified including 18,979 (77%) women with squamous cell carcinomas, 4103 (17%) with adencarcinomas, and 1480 (6%) with adenosquamous tumors. Women with adenocarcinomas were younger, more often white, and more frequently married than patients with squamous cell tumors (p < 0.0001 for all). Patients with adenocarcinomas were more likely to present with early-stage disease (p < 0.0001). At diagnosis, 26.7% of women with adenocarcinomas had stage IB1 tumors compared to 16.9% of those with squamous cell carcinomas. Among women with early-stage (IB1-IIA) tumors, patients with adenocarcinomas were 39% (HR = 1.39; 95% CI, 1.23-1.56) more likely to die from their tumors than those with squamous cell carcinomas. For patients with advanced-stage disease (stage IIB-IVA) women with adenocarcinomas were 21% (HR = 1.21; 95% CI, 1.10-1.32) more likely to die from their tumors than those with squamous neoplasms. Five-year survival for stage IIIB neoplasms five-year survival was 31.3% (95% CI, 29.2-33.3%) for squamous tumors vs. 20.3% (95% CI, 14.2-27.1%) for adenocarcinomas.

Conclusion

Cervical adenocarcinomas are more common in younger women and white patients. Adenocarcinoma histology negatively impacts survival for both early and advanced-stage carcinomas.     

Evaluation of Fanconi anaemia genes FANCA, FANCC and FANCL in cervical cancer susceptibility

Objective

Disrupting the function of any of the 13 Fanconi anaemia (FA) genes causes a DNA repair deficiency disorder, with patients being susceptible to a number of cancer types. Variation in the family of FA genes has been suggested to affect risk of cervical cancer. The current study evaluates the influence of three genes in the FA pathway on cervical cancer risk in Swedish women.

Methods

TagSNPs in FANCA, FANCC and FANCL were selected using the Tagger algorithm in Haploview. A total of 81 tagSNPs were genotyped in 782 cases (CIN3 or ICC) and 775 controls using the Illumina GoldenGate Assay and statistically analyzed for association with cervical cancer.

Results

72 SNPs were successfully genotyped in > 98% of the samples. Nominal associations were detected for FANCA rs11649196 (p = 0.05) and rs4128763 in FANCC (p = 0.02). The associations did not withstand correction for multiple testing.

Conclusions

The current study does not support that genetic variation in FANCA, FANCC or FANCL genes affects susceptibility to cervical cancer in the Swedish population.     

Robotically assisted fluorescence-guided lymph node mapping with ICG for gynecologic malignancies: a feasibility study

Objective

Traditional techniques of sentinel lymph node (SLN) mapping for endometrial and cervical cancer present challenges which may be overcome with newer technologies such as near infrared (NIR) imaging of the fluorescent dye Indocyanine green (ICG). We performed a feasibility and dose-finding study to define the dose of ICG required to identify pelvic and para-aortic sentinel lymph nodes with robotically assisted endoscopic NIR imaging after cervical injection.

Methods

20 subjects with cervical or endometrial carcinoma were prospectively enrolled for SLN mapping. ICG was injected into the cervical stroma at 3 o'clock and 9 o'clock Data was collected for the number of nodes identified, the location of SLN's, the duration of procedure and the pathology characteristics of the SLN's compared to the non-sentinel lymph nodes.

Results

20 subjects received cervical injection with at least one SLN observed in 17 subjects. 15 of the 17 subjects who received 1 mg injections of ICG mapped a SLN for an observed detection rate of 88% (95% CI is (64%,99%)). A median of 4.5 SLN's was identified per patient. Three patients had lymphatic metastases, one of whom had a positive SLN. No adverse events were identified.

Conclusions

A 1 mg cervical injection of ICG identified a SLN in 88% of patients (95% CI is (64%, 99%)). Robotically assisted fluorescence imaging is a feasible, safe, time efficient and reliable method for lymphatic mapping in early stage cervical and endometrial cancer.     

A model for prediction of parametrial involvement and feasibility of less radical resection of parametrium in patients with FIGO stage IB1 cervical cancer

Objective

The objective of this study was to evaluate the potential risk factors associated with parametrial invasion and to identify preoperatively a subgroup of patients at low risk for parametrial involvement who could be appropriate candidates for less radical surgery in FIGO stage IB1 cervical cancer.

Methods

We retrospectively reviewed the medical records of 317 FIGO stage IB1 cervical cancer patients undergoing class III radical hysterectomy and bilateral pelvic lymphadenectomy. Clinocopathologic factors associated with parametrial invasion were analyzed and the risk criteria predicting parametrial involvement were calculated using a logistic regression model.

Results

Of 317 patients, 17 patients (5.4%) had parametrial involvement. Tumor size > 3 cm (OR, 3.80; [95% CI, 1.19-12.06]; p = 0.02) and pelvic lymph node metastasis (OR, 3.02; [95% CI, 1.04-8.79]; p = 0.04) were independent pathologic factors for parametrial invasion on multivariate analysis. Significant preoperative factors associated with parametrial involvement were tumor size > 3 cm (OR, 4.29; [95% CI, 1.43-12.89]; p < 0.01) and serum SCC Ag level > 1.40 ng/mL (OR, 3.27; [95% CI, 1.11-9.69]; p = 0.03). We identified 185 low-risk (tumor size ≤ 3 cm and SCC ≤ 1.4 ng/mL) and 132 high-risk (tumor size > 3 cm and/or SCC > 1.4 ng/mL) patients. The rates of parametrial involvement in low- and high-risk patients were 1.1% and 11.4%, respectively (p < 0.01).

Conclusions

In this dataset, a model using tumor size and SCC Ag level is highly predictive of parametrial involvement in patients with stage IB1 cervical cancer and may identify candidates for less radical parametrial resection.     

How are women with high grade Pap smear abnormalities managed? A population based study

Objective

This population based study investigates the patterns of care women with high grade cervical dysplasia receive.

Methods

The study population includes women with a first time diagnosis of a high grade dysplasia (ASC-H, AGUS, HSIL, malignancy, carcinoma) from 2000 to 2005 as identified in a centralized cervical smear database. Record linkages were then carried out to other databases of health care services to characterize management.

Results

Women (43,712) with a high grade dysplasia had a mean age of 37.6. HSIL and AGC accounted for 55% and 33% of abnormalities, respectively. The mean time to referral to colposcopy services ranged from 6 to 24 weeks. Women (1195) were diagnosed with an underlying cervical cancer with a mean time to diagnosis of 26, 26, 17, 6, and 3 weeks for the cytologic abnormality of ASC-H, AGUS, HSIL, malignancy, and carcinoma, respectively. Women (559) were diagnosed with endometrial cancer. The mean time to diagnosis from index Pap was 16, 5.3 and 1.5 weeks for AGC, malignancy, and carcinoma on Pap test, respectively. The percentage of patients with a high grade Pap smear who had no follow-up all up to a 2-year window from index Pap was 5.4, 74, 19, 1.22, and 0.18% for ASC-H, AGUS, HSIL, malignancy and carcinoma on Pap, respectively.

Conclusions

The mean time to referral to colposcopy and rates of loss to follow-up for high grade smears are influenced by cytologic nomenclature. Explicit language is recommended for national guidelines to reduce the prolonged time in the workup of patients who may have serious premalignant and malignant lesion of the reproductive tract.     

Cancerous inhibitor of protein phosphatase 2A is overexpressed in cervical cancer and upregulated by human papillomavirus 16 E7 oncoprotein

Objectives

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein stabilizing c-Myc and promoting cell proliferation and transformation. Here we investigated the role of CIP2A in cervical cancer in vivo and in vitro.

Methods

CIP2A expression was assessed in normal cervical, cervical intraepithelial neoplasia (CIN) I to III and cervical cancer tissues by immunohistochemistry and RT-PCR. Cell growth was explored by cell proliferation assay, colony formation assay and anchorage-independent growth in soft agar after inhibition of CIP2A by siRNA in HeLa, SiHa and Caski cells. Crosstalk of CIP2A and HPV16 E7 was investigated by immunohistochemistry in cervical cancer tissues and by real-time PCR and western blot analysis after HPV16 E7 inhibition by siRNA in SiHa cells.

Results

CIP2A was transcribed in 73.3% of cervical cancer tissues (n = 15) but not in normal cervical tissues (n = 8). CIP2A protein was detected in 52.8% of cervical cancer (n = 72) and 12.5% of CIN III tissues (n = 24) but not in normal (n = 15), CIN I (n = 21) or CIN II samples (n = 25). CIP2A protein level was positively associated with HPV16 E7 level in cervical cancer tissues. CIP2A expression was markedly reduced after E7 depletion. Moreover, CIP2A depletion reduced c-Myc protein level and impaired proliferation and growth of cervical cancer cells.

Conclusions

CIP2A is overexpressed in cervical cancer and promotes the malignant growth of cervical cancer cells. Its expression is upregulated by HPV16 E7. Therefore, CIP2A plays an important role in carcinogenisis of cervical cancer and shows promise for the diagnosis and treatment of cervical cancer.     

Cryotherapy for HPV clearance in women with biopsy-confirmed cervical low-grade squamous intraepithelial lesions

Objective

To compare the clearance rate of HPV infection among women aged older than 30 years with biopsy-confirmed cervical low-grade squamous intraepithelial lesions (LSIL) 1 year after cryotherapy with the spontaneous clearance rate (observation).

Method

HPV DNA typing by polymerase chain reaction and reverse line blot hybridization were used to identify 14 high-risk types and 23 low-risk types. HPV DNA sequencing was also used for other types.

Result

Between December 2007 and March 2009, 100 women were recruited to the study and 60 cases had positive results on HPV testing. Twenty-nine patients were randomly allocated to the cryotherapy group and 31 to the observation group. At 1 year, 89.7% (26/29; 95% CI, 78.6-100%) of the cryotherapy group and 90.3% (28/31; 95% CI, 79.9-100%) of the observation group had negative results on HPV testing (0.6% difference; 95% CI, -15.8 to 14.6%, P = 0.94).

Conclusion

Cryotherapy failed to increase the clearance of prevalent HPV infections among women with LSIL, although in both arms the clearance rates were above 80%. However, in coupling with visual inspection with acetic acid as a single visit approach, its effect on prevention of HSIL and cervical cancer is still promising. Therefore, cryotherapy should not be withdrawn from such programs. (ClinicalTrials.gov Identifier: NCT00566579).