Britt K. Erickson

New insights into cervical cancer screening

Worldwide, cervical cancer is a leading cause of cancer related morbidity and mortality. For over 50 years, cervical cytology has been the gold standard for cervical cancer screening. Because of its profound effect on cervical cancer mortality in nations that have adopted screening programs, the Pap smear is widely accepted as the model screening test. Since its introduction, many studies have analyzed the Pap smear and found that it is not without its shortcomings including low sensitivity for detection of cervical intraepithelial neoplasia 2/3. Additionally, the discovery of infection with the human papillomavirus (HPV) as a necessary step in the development of cervical cancer has led to the development of HPV testing as an adjunct to cytology screening. More recently, researchers have compared HPV testing and cytology in the primary screening of cervical cancer. In this review, we will discuss cytologic testing limitations, the role of HPV DNA testing as an alternative screening tool, the impact of the HPV vaccine on screening, and future directions in cervical cancer screening.

Cervical cancer screening: evidence behind the guidelines

Cervical cancer screening involves a complex process of cytology, human papillomavirus (HPV) testing, colposcopy, and a multitude of algorithms for the identification of preinvasive disease and prevention of invasive disease. High-risk HPV is a prerequisite for the development of almost all types of cervical cancer; therefore, a test for high-risk HPV has become an integral part of new screening strategies. Major changes to screening guidelines in the last decade include initiation of screening at age 21 years, conservative management of young women with abnormal cytology, extended screening intervals for women age ≥30 years, and cessation of screening in low-risk women at age 65 years. This review will focus on the evidence that has led to the current evidence-based guidelines. Evidence regarding primary HPV testing as well as postvaccine-based screening strategies will also be reviewed.

Reasons for failure to deliver National Comprehensive Cancer Network (NCCN)-adherent care in the treatment of epithelial ovarian cancer at an NCCN cancer center.

OBJECTIVE The National Comprehensive Cancer Network (NCCN) has established guidelines for treating epithelial ovarian cancer (EOC) which includes cytoreductive surgery and platinum and taxane-based chemotherapy (CT). The objective of this study was to determine the reasons for failure to deliver NCCN-adherent care at an NCCN cancer center serving a diverse racial and socioeconomic population. METHODS Medical records of women with EOC diagnosed between 2004 and 2009 were reviewed for demographic, clinical, tumor, treatment, and survival data. Independent reviewers determined if their treatment met criteria for being NCCN-adherent. Progression-free survival (PFS) and overall survival (OS) were calculated with Kaplan-Meier estimates and compared with the log-rank test. RESULTS 367 patients were identified. 79 (21.5%) did not receive NCCN-adherent care. Non-adherent CT in 75 patients was the most common reason for failure to receive NCCN-adherent care. 39 patients did not complete CT due to treatment toxicities or disease progression. 12 patients received single agent CT only and 4 received no CT due to comorbidities. 2 patients declined CT. 18 patients died in the postoperative period without receiving CT. 8 patients did not undergo cytoreduction due to disease progression or comorbidities. PFS and OS were improved in the NCCN-adherent cohort (PFS: 5.7 vs. 18.3 months, p<.005) (OS: 11.4 vs. 49.5 months, p<.005). CONCLUSIONS The vast majority of patients at an NCCN cancer center received NCCN-adherent treatment. Reasons for failure to receive NCCN-adherent care were variable, but most did not receive chemotherapy in accordance with guidelines due to comorbidities or disease progression.

Diabetes mellitus and ovarian cancer: More complex than just increasing risk ☆

OBJECTIVE Diabetes mellitus (DM) is a risk factor for endometrial cancer and is associated with poorer outcomes in breast and colon cancers. This association is less clear in epithelial ovarian cancer (EOC). We sought to examine the effect of DM on progression-free (PFS) and overall survival (OS) in women with EOC. METHODS A retrospective cohort study of EOC patients diagnosed between 2004 and 2009 at a single institution was performed. Demographic, pathologic and DM diagnosis data were abstracted. Pearson chi-square test and t test were used to compare variables. The Kaplan-Meier method and the log rank test were used to compare PFS and OS between non-diabetic (ND) and DM patients. RESULTS 62 (17%) of 367 patients had a diagnosis of DM. No differences in age, histology, debulking status, or administration of intraperitoneal chemotherapy between ND and DM patients were present, although there were more stage I and IV patients in the ND group (p=0.04). BMI was significantly different between the two groups (ND vs. DM, 27.5 vs. 30.7kg/m(2), p<0.001). While there were no differences in survival based on BMI, diabetic patients had a poorer PFS (10.3 vs. 16.3months, p=0.024) and OS (26.1 vs. 42.2months, p=0.005) compared to ND patients. Metformin use among diabetic patients did not appear to affect PFS or OS. CONCLUSIONS EOC patients with DM have poorer survival than patients without diabetes; this association is independent of obesity. Metformin use did not affect outcomes. The pathophysiology of this observation requires more inquiry.

Human papillomavirus: what every provider should know

Persistence of human papillomavirus (HPV) infection is necessary for the development of cervical cancer. Additionally, infection with HPV is implicated in the majority of cases of other genital tract malignancies including vulvar, penile, and vaginal cancer. HPV testing and vaccination are a routine part of obstetrical/gynecological clinical practice. With an enhanced public awareness of HPV infections, many patients turn to their obstetricians/gynecologists with questions about transmission, testing, and prevention. In this review, we will discuss the biology of HPV, epidemiology of disease, methods and indications for testing, and vaccination strategies.

Detection of somatic TP53 mutations in tampons of patients with high-grade serous ovarian cancer

OBJECTIVE: To investigate whether tumor cells could be detected in the vagina of women with serous ovarian cancer through TP53 analysis of DNA samples collected by placement of a vaginal tampon. METHODS: Women undergoing surgery for a pelvic mass were identified in the gynecologic oncology clinic. They placed a vaginal tampon before surgery, which was removed in the operating room. Cells were isolated and DNA was extracted from both the cells trapped within the tampon and the primary tumor. In patients with serous carcinoma, the DNA was interrogated for the presence of TP53 mutations using a method capable of detecting rare mutant alleles in a mixture of mutant and wild-type DNA. RESULTS: Thirty-three patients were enrolled. Eight patients with advanced serous ovarian cancer were included for analysis. Three had a prior tubal ligation. TP53 mutations were identified in all eight tumor samples. Analysis of the DNA from the tampons revealed mutations in three of the five patients with intact tubes (sensitivity 60%) and in none of the three patients with tubal ligation. In all three participants with mutation detected in the tampon specimen, the tumor and the vaginal DNA harbored the exact same TP53 mutation. The fraction of DNA derived from exfoliated tumor cells ranged from 0.01% to 0.07%. CONCLUSION: In this pilot study, DNA derived from tumor was detected in the vaginas of 60% of patients with ovarian cancer with intact fallopian tubes. With further development, this approach may hold promise for the early detection of this deadly disease. LEVEL OF EVIDENCE: III

Cost-effectiveness analysis of sentinel lymph node biopsy in the treatment of early-stage vulvar cancer

Objective The objective of this study was to determine the costs and outcomes of inguinal-femoral lymph node dissection (IF-LND) versus sentinel lymph node biopsy (SLNB) for the management of early-stage vulvar cancer. Methods A cost-effectiveness model compared 2 different strategies for the management of early-stage vulvar cancer: (1) vulvectomy and SLNB and (2) vulvectomy and IF-LND. Probabilities of inguinal-femoral node metastases and recurrence rates associated with each strategy were estimated from published data. Actual payer costs of surgery and radiation therapy were obtained using 2012 CPT codes and Medicare payment information. Rates and costs of postoperative complications including lymphedema, lymphocyst formation, and infection were estimated and included in a separate model. Cost-effectiveness ratios were determined for each strategy. Sensitivity analyses were performed to evaluate pertinent uncertainties in the models. Results For the estimated 3000 women diagnosed annually with early-stage vulvar cancer in the United States, the annual cost of the SLNB strategy is

Low yield of residual vulvar carcinoma and dysplasia upon re-excision for close or positive margins

65.2 million compared with

Black race independently predicts worse survival in uterine carcinosarcoma

76.8 million for the IF-LND strategy. Three-year inguinal-femoral recurrence-free survival was similar between groups (96.9% vs 97.3%). This translates into a lower cost-effectiveness ratio for the SLNB strategy (

Survey of robotic surgery credentialing requirements for physicians completing OB/GYN residency.

22,416), compared with the IF-LND strategy (