Capsid display of a conserved human papillomavirus L2 peptide in the adenovirus 5 hexon protein: a candidate prophylactic hpv vaccine approach.

BACKGROUND: Infection by any one of 15 high risk human papillomavirus (hrHPV) types causes most invasive cervical cancers. Their oncogenic genome is encapsidated by L1 (major) and L2 (minor) coat proteins. Current HPV prophylactic vaccines are composed of L1 virus-like particles (VLP) that elicit type restricted immunity. An N-terminal region of L2 protein identified by neutralizing monoclonal antibodies comprises a protective epitope conserved among HPV types, but it is weakly immunogenic compared to L1 VLP. The major antigenic capsid protein of adenovirus type 5 (Ad5) is hexon which contains 9 hypervariable regions (HVRs) that form the immunodominant neutralizing epitopes. Insertion of weakly antigenic foreign B cell epitopes into these HVRs has shown promise in eliciting robust neutralizing antibody responses. Thus here we sought to generate a broadly protective prophylactic HPV vaccine candidate by inserting a conserved protective L2 epitope into the Ad5 hexon protein for VLP-like display. METHODS: Four recombinant adenoviruses were generated without significant compromise of viral replication by introduction of HPV16 amino acids L2 12-41 into Ad5 hexon, either by insertion into, or substitution of, either hexon HVR1 or HVR5. RESULTS: Vaccination of mice three times with each of these L2-recombinant adenoviruses induced similarly robust adenovirus-specific serum antibody but weak titers against L2. These L2-specific responses were enhanced by vaccination in the presence of alum and monophoryl lipid A adjuvant. Sera obtained after the third immunization exhibited low neutralizing antibody titers against HPV16 and HPV73. L2-recombinant adenovirus vaccination without adjuvant provided partial protection of mice against HPV16 challenge to either the vagina or skin. In contrast, vaccination with each L2-recombinant adenovirus formulated in adjuvant provided robust protection against vaginal challenge with HPV16, but not against HPV56. CONCLUSION: We conclude that introduction of HPV16 L2 12-41 epitope into Ad5 hexon HVR1 or HVR5 is a feasible method of generating a protective HPV vaccine, but further optimization is required to strengthen the L2-specific response and broaden protection to the more diverse hrHPV.

Outcomes in Ovarian Cancer among Hispanic Women Living in the United States: A Population-Based Analysis.

Introduction. Ovarian cancer is the deadliest gynecologic cancer in the United States. There is limited data on presentation and outcomes among Hispanic women with ovarian cancer. Objective. To investigate how ovarian cancer presents among Hispanic women in the USA and to analyze differences in presentation, staging, and survival between Hispanic and non-Hispanic women with ovarian cancer. Methods. Data from January 1, 2000 to December 31, 2004 were extracted from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database. Results. The study sample comprised 1215 Hispanics (10%), 10 652 non-Hispanic whites (83%), and 905 non-Hispanic blacks (7%). Hispanic women were diagnosed with ovarian cancer at a younger age and earlier stage when compared to non-Hispanic whites, non-Hispanic blacks; P < 0.001. Similar proportion of Hispanics (33%), non-Hispanic whites (32%), and non-Hispanic blacks (24%) underwent lymphadenectomy; P < 0.001. Hispanics with epithelial ovarian cancer histology had longer five-year survival of 30.6 months compared to non-Hispanic whites (22.8 months) and non-Hispanic blacks (23.3 months); P = 0.001. Conclusion. Hispanic women with ovarian cancer have a statistically significantly longer median survival compared to whites and blacks. This survival difference was most apparent in patients with epithelial cancers and patients with stage IV disease.

Sexual activity and function in women with and without pelvic floor disorders.

INTRODUCTION AND HYPOTHESIS: We describe differences in sexual activity and function in women with and without pelvic floor disorders (PFDs). METHODS: Heterosexual women ≥40 years of age who presented to either urogynecology or general gynecology clinics at 11 clinical sites were recruited. Women were asked if they were sexually active with a male partner. Validated questionnaires and Pelvic Organ Prolapse Quantification (POP-Q) examinations assessed urinary incontinence (UI), fecal incontinence (FI), and/or pelvic organ prolapse (POP). Sexual activity and function was measured by the Female Sexual Function Index (FSFI). Student's t test was used to assess continuous variables; categorical variables were assessed with Fisher's exact test and logistic regression. Univariate and multivariate analyses were used to assess the impact of pelvic floor disorders (PFDs) on FSFI total and domain scores. RESULTS: Five hundred and five women met eligibility requirements and gave consent for participation. Women with and without PFDs did not differ in race, body mass index (BMI), comorbid medical conditions, or hormone use. Women with PFDs were slightly older than women without PFDs (55.6 + 10.8 vs. 51.6 + 8.3 years, P <0.001); all analyses were controlled for age. Women with PFDs were as likely to be sexually active as women without PFDs (61.6 vs. 75.5 %, P = 0.09). There was no difference in total FSFI scores between cohorts (23.2 + 8.5 vs. 24.4 + 9.2, P = 0.23) or FSFI domain scores (all P = NS). CONCLUSION: Rates of sexual activity and function are not different between women with and without PFDs.

Introduction of checklists at daily progress notes improves patient care among the gynecological oncology service.

OBJECTIVES: To evaluate the impact of the introduction of checklists at the daily progress note to improve patient care among gynecologic oncology patients. METHODS: A progress note incorporating checklists that were pertinent for our patient population was developed with input obtained from all staff involved on patients care. The form was approved by the hospital. The average length of stay, compliance with prophylactic guidelines (anticoagulation, peptic ulcer disease), reason for admission, and readmission rate were compared among the preimplementation and postimplementation periods. RESULTS: A total of 492 discharge summaries were evaluated through the study period (267 for the preimplementation period and 225 for the postimplementation period). The mean length of stay was of 4.46 days for the preimplementation and 3.46 days for the postimplementation period (P = 0.007). TEDs/SCDs were not used in 9.3% of the patients in the pre group versus 0.6% in the post group (P < 0.001). DVT prophylaxis was given to 30.1% of the pre group versus 34.8% of the post group (P = 0.0013). The administration of PUD prophylaxis also increased from 28.3% in the pre group to 40.2% of the post group (P < 0.001). There was a decrease in the nonsurgical admissions from 22.2% in the pre group versus 14.6% in the post group (P = 0.049). CONCLUSIONS: The use of checklists in daily progress notes enhances patient care by improving the delivery of routine care that is often overlooked in the light of major medical issues.

The risk of umbilical hernia and other complications with laparoendoscopic single-site surgery.

STUDY OBJECTIVE: To estimate the risk of umbilical hernia and other latent complications in women who underwent laparoendoscopic single-site surgery (LESS) for a gynecologic indication. DESIGN: Retrospective, nonrandomized clinical study (Canadian Task Force classification II-2). SETTING: Four tertiary care academic medical centers. PATIENTS: Women undergoing LESS for a benign or malignant gynecologic indication from 2009 to 2011. INTERVENTIONS: A total of 211 women underwent LESS via a single 1.5- to 2.0-cm umbilical incision. All surgeries were performed by advanced gynecologic laparoscopists. Incisions were repaired with a running, delayed absorbable suture. Subject demographics and clinical variables were collected and surgical outcomes analyzed. MEASUREMENTS AND MAIN RESULTS: Median age and body mass index were 45 years and 30 kg/m(2), respectively. Approximately half of study subjects underwent a hysterectomy with or without salpingo-oophorectomy, and 15% had a diagnosis of cancer. Overall, 0.9% of women were diagnosed with a preoperative umbilical hernia, and 2.4% of women experienced a major perioperative complication. After a median postoperative follow-up time of 16 months, 2.4% had development of an umbilical hernia. However, 4/5 of these women had significant risk factors for fascial weakening independent of LESS, including requirement for a second abdominal surgery in 1 subject and a cancer diagnosis with postoperative chemotherapy administration in 2 subjects. When these subjects deemed "high risk" for incisional disruption were excluded from the analysis, the umbilical hernia rate was 0.5% (1/207). On univariable analysis, obesity was the only factor associated with complications (p = .04). CONCLUSION: When performed by advanced laparoscopic surgeons, laparoendoscopic single-site gynecologic surgery is associated with a low risk of major adverse events. Additionally, the overall umbilical hernia rate was 2.4% and was lower (0.5%) in subjects without significant comorbidities.

Analysis of racial disparities in stage IIIC epithelial ovarian cancer care and outcomes in a tertiary gynecologic oncology referral center.

OBJECTIVE: To examine disparities in delivery of care and survival according to racial classification among White and African-American women with Stage IIIC epithelial ovarian cancer undergoing initial treatment in a tertiary referral center setting. METHODS: All consecutive patients diagnosed with Stage IIIC epithelial ovarian cancer between 1/1/95 and 12/31/08 were identified and clinic-pathologic variables retrospectively collected. Differences in initial treatment paradigm, surgical and adjuvant therapy, and overall survival according to racial classification were assessed by univariate and multivariate analyses. RESULTS: A total of 405 patients (White, n=366; African-American, n=39) were identified. There were no significant differences according to racial classification in age, CA125, ASA class, histology, tumor grade, the frequency of initial surgery (90.4% vs 82.1%, p=0.06), optimal residual disease (73.0% vs 69.2%, p=0.28), no gross residual disease (51.4% vs 53.8%, p=0.49), and platinum-taxane chemotherapy (88.3% vs 87.2%, p=0.55). The median overall survival for White patients was 50.5 months (95%CI=43.2-57.9 months), compared to 47.0 (95%CI=36.2-57.8) months for African-Americans (p=0.57). On multivariate analysis, age, tumor grade 3, serum albumin <3.0 g/dl, platinum-based chemotherapy, and no gross residual disease were independently associated with overall survival, while African-American race was not (HR=1.06, 95%CI=0.61-1.79). CONCLUSIONS: Among women undergoing initial treatment for ovarian cancer at a tertiary referral center, African-American patients were as likely as White patients to undergo cytoreductive surgery, be left with minimal post-surgical residual disease, and receive appropriate chemotherapy. With equal access to gynecologic oncology care and multidisciplinary cancer resources, the survival disparities according to race observed in population-based studies are largely mitigated.

Hormone replacement therapy in gynecologic cancer survivors: why not?

PURPOSE: As a result of treatment, many women with gynecologic malignancies will go through menopause and display climacteric symptoms at an earlier age than occurs naturally. Iatrogenic menopause may adversely affect quality of life and health outcomes in young female cancer survivors. Hormone replacement therapy (HRT) has often been withheld from women with gynecologic cancer because of concern that it might increase the risk of relapse or the development of new primary cancers. The purpose of this review was to examine the published literature on menopause management in gynecologic cancer survivors and highlight the risks and benefits of conventional and alternative HRT in this population. METHODS: A comprehensive literature search of English language studies on menopause management in gynecologic cancer survivors and women with a hereditary predisposition to a gynecologic malignancy was performed in MEDLINE databases through December 2010. RESULTS: Both our review and a 2008 Cochrane review of randomized trials on the effects of long-term HRT demonstrate that for menopausal women in their 40s or 50s with and without gynecologic cancer, the absolute risks of estrogen-only HRT are low. Several prospective observational studies and randomized trials on HRT use in women with a genetic predisposition for or development of a gynecologic malignancy suggest benefits in quality of life with no proven adverse oncologic effects as a result of short-term HRT use. CONCLUSION: In select women, it is reasonable to discuss and offer conventional HRT for the amelioration of menopausal symptoms and to improve quality of life. HRT does not appear to increase the risk of gynecologic cancer recurrences; however, this conclusion was largely based on observational data and smaller prospective studies.

Racial disparities in ovarian cancer surgical care: a population-based analysis.

OBJECTIVE: To investigate differences according to racial classification in the frequency of ovarian cancer-related surgical procedures and in access to high-volume surgical providers among women undergoing initial surgery for ovarian cancer. METHODS: The Maryland Health Services Cost Review Commission database was accessed for women age >18years undergoing a surgical procedure that included oophorectomy for a malignant ovarian neoplasm between 7/1/01 and 6/30/09. Multivariate logistic regression analyses were used to evaluate for differences in the likelihood of selected surgical procedures and access to high-volume surgical providers (surgeons≥10 cases/year; hospitals≥20 case/year) according racial classification. RESULTS: A total of 2487 patients were identified who underwent a primary surgical procedure that included oophorectomy for a malignant ovarian neoplasm: White=1884 (75.4%), African-American=400 (16.1%), and other/unknown=203 (8.2%). Compared to White patients, African-American patients were significantly younger (mean age 55.4years vs 59.9years, P<0.0001) and less likely to have commercial insurance (28.5% vs 39.5%, p<0.0001). Compared to White patients, African-American racial classification was associated with a statistically significant and independent lower likelihood of hysterectomy (OR=0.53, 95%CI=0.42-0.66, p<0.0001), colon resection (OR=0.65, 95%CI=0.48-0.87, p=0.004), lymphadenectomy (OR=0.67, 95%CI=0.50-0.91, p=0.01), and surgery by a high-volume surgeon (OR=0.55, 95%CI=0.44-0.69, p<0.0001). CONCLUSIONS: Among women undergoing initial surgery for ovarian cancer, African-American patients are significantly less likely to be operated on by a high-volume surgeon and to undergo important ovarian cancer-specific surgical procedures compared to White patients.

Molecular pathogenesis of cervical cancer.

INTRODUCTION: Cervical cancer is a sexually transmitted disease that results from infection with oncogenic types of human papillomavirus (HPV). Oncogenic HPV DNA is found in over 95% of invasive cervical cancers worldwide. Cervical cancer is a leading cause of cancer deaths in developing countries because of high HPV infection rates and lack of comprehensive cervical Pap smear testing of susceptible women. Vaccination against HPV prevents the acquisition of cervical dysplastic lesions among eligible women who have not already acquired the vaccine-specific HPV types. METHODS: Literature review of the epidemiology, infection cycle, viral gene function and current vaccines related to the oncogenic types of the human papillomavirus (HPV). CONCLUSION: Enhanced understanding of HPV and population-based measures offer the best hope of limiting worldwide mortality due to cervical cancer. The development of therapeutic cervical cancer vaccines and/or virus-targeted drug therapies would be a giant step forward.

Laparoendoscopic single-site surgery (LESS) in gynecology: a multi-institutional evaluation.

OBJECTIVE: The study objectives were to determine the surgical outcomes of a large series of gynecology patients treated with laparoendoscopic single-site surgery (LESS). STUDY DESIGN: This was a retrospective, multi-institutional analysis of gynecology patients treated with LESS in 2009. Patients underwent surgery via a single 1.5- to 2.5-cm umbilical incision with a multichannel single port. RESULTS: A total of 74 women underwent LESS. Procedures were performed for benign pelvic masses (n = 39), endometrial hyperplasia (n = 9), endometrial (n = 15) and ovarian (n = 6) cancers, and nongynecologic malignancies (n = 5). Median patient age and body mass index were 47 years and 28, respectively. A Pearson product-moment correlation coefficient was computed and demonstrated a significant linear relationship between the operating time and number of cases for cancer staging (r = -0.71; n = 26; P < .001) and nonstaging (r = -0.78; n = 48; P < .002) procedures. Perioperative complications were low (3%). CONCLUSION: LESS is feasible, safe, and reproducible in gynecology patients with benign and cancerous conditions. Operative times are reasonable and can be decreased with experience.

Hypertrophic cervical elongation: clinical and histological correlations.

INTRODUCTION AND HYPOTHESIS: The objective of this study is to define the diagnosis of hypertrophic cervical elongation clinically and to perform histochemical and histological evaluations of patients with and without hypertrophic cervical elongation. METHODS: This prospective study was conducted at Louisiana State University between December 2005 and May 2008. Fourteen women with cervical elongation and 28 women without prolapse were studied. RESULTS: The amounts of elastin, collagen, and smooth muscle did not differ between study and control groups. Estrogen and progesterone receptor content in cervical elongation were elevated compared to the cervix of women without prolapse. Hypertrophic cervical elongation was defined as the difference between point C and point D of the Pelvic Organ Prolapse Quantification system greater than 8 cm. CONCLUSIONS: Estrogen and progesterone receptor levels are greater in women with hypertrophic cervical elongation compared with a normal cervix.

Predicting the outcome of cytoreductive surgery for advanced ovarian cancer: a review.

INTRODUCTION: Ovarian cancer is the leading cause of gynecologic cancer-related mortality in the United States. Surgical cytoreduction is the cornerstone of current treatment in patients with advanced disease, but it offers the best chances for overall survival when optimal cytoreduction is achieved. Clinicopathological and radiological models for predicting optimal resectability have not been universally applicable. OBJECTIVE: To summarize the existing surgical data on current serologic, radiological, and surgical tools used to predict the resectability of advanced ovarian cancer. METHODS: Systematic review of surgical studies on primary cytoreductive surgery for advanced ovarian cancer reported in the English-language literature between 1980 and 2009. RESULTS: Seventeen retrospective studies using cancer antigen 125, and 8 retrospective studies using radiological imaging modalities to predict resectability of advanced ovarian cancer were reviewed. Five laparoscopic-based reports of ovarian cancer resectability were also reviewed as well as 5 studies examining the role of clinicopathological variables affecting surgical cytoreductive ability. These studies were analyzed according to the rate of optimal cytoreduction achieved and the reported sensitivity, specificity, accuracy, and predictive values of predictive parameters described. Finally, the various conclusions were compared. CONCLUSIONS: The rates of optimal cytoreduction vary among surgeons. A universally applicable clinical model that can predict which patients will undergo optimal cytoreduction remains elusive. More research is needed to devise a set of uniform criteria that can be used to predict ovarian cancer resectability among different patient populations.

Does vaginal size impact sexual activity and function?

INTRODUCTION AND HYPOTHESIS: This study seeks to determine if total vaginal length (TVL) or genital hiatus (GH) impact sexual activity and function. METHODS: Heterosexual women >or= 40 years were recruited from urogynecology and gynecology offices. TVL and GH were assessed using the Pelvic Organ Prolapse Quantification exam. Women completed the Female Sexual Function Index (FSFI) and were dichotomized into either normal function (FSFI total > 26) or sexual dysfunction (FSFI

Complications of transvaginal monofilament polypropylene mesh in pelvic organ prolapse repair.

INTRODUCTION AND HYPOTHESIS: This study aimed to document intraoperative and postoperative complications associated with the use of transvaginal polypropylene mesh in the repair of pelvic organ prolapse (POP). METHODS: This is a retrospective review of 127 cases of transvaginal repair of POP using synthetic mesh. RESULTS: Mean postoperative value (+/-SD) for pelvic organ prolapse quantification (POPQ) measurements Aa, Ap, and C were: -2.4 +/- 1.1 (cm), -2.4 +/- 0.9 (cm), and -7.7 +/- 1.2 (cm), respectively. The difference between preoperative and postoperative values of these points was significant (p < 0.0001). Mesh erosion rate was 13/127 (10.2%) with significant correlation between mesh erosion and concurrent vaginal hysterectomy (p = 0.008). Combined anterior and posterior vaginal mesh surgery increased the risk of intraoperative bleeding and blood transfusion (p < 0.05). CONCLUSIONS: Concurrent vaginal hysterectomy is associated with increased risk of vaginal mesh erosion. Combined anterior and posterior vaginal mesh repair is an increased risk factor for intraoperative bleeding and blood transfusion.

Urinary tract injury during hysterectomy based on universal cystoscopy.

OBJECTIVE: To estimate the incidence and location of injury to the urinary tract during hysterectomy for benign gynecologic disease. METHODS: This was a prospective clinical study in an academic environment performed at three sites. Diagnostic cystourethroscopy was performed on all patients after hysterectomy for benign disease. RESULTS: Eight hundred thirty-nine patients were enrolled. The incidence of urinary tract injury associated with hysterectomy for benign disease was 4.3% (39 of 839 cases). The rate of bladder injury was 2.9% (24 of 839 cases), and rate of ureteral injury was 1.8% (15 of 839 cases). There were three cases of simultaneous bladder and ureteral injuries, resulting in a cumulative injury rate of 4.3%. The injury detection rate using intraoperative diagnostic cystoscopy was 97.4% (817 of 839 cases). The most common site of injury to the ureter was at the junction of the ureter and the uterine artery in 80% (12 of 15 cases) of ureteral injuries. Transection and kinking injuries were the most frequent type of injury. There were 21 cases of subnormal dye efflux from the ureteral orifices, with no subsequent injury detected on further evaluation. CONCLUSION: Ureteral injury occurred most commonly at the level of the uterine artery, and transection and kinking injuries were most frequent. Diminished dye efflux from ureteral orifices was not associated with injury. LEVEL OF EVIDENCE: III.