While women await surgery for type I endometrial cancer, depot medroxyprogesterone acetate reduces tumor glandular cellularity.

BACKGROUND: Multiple population-level studies have demonstrated an adverse effect of long wait times to surgery on survival for women with endometrial cancer. Other retrospective and nonrandomized prospective studies have shown that preoperative administration of depot medroxyprogesterone acetate decreases tumor glandular cellularity, which may be a surrogate marker for clinically meaningful tumor response. OBJECTIVE: We sought to determine whether preoperative injection with depot medroxyprogesterone acetate decreases tumor glandular cellularity when compared to placebo injection in women awaiting hysterectomy for endometrial intraepithelial neoplasia or type I endometrial cancer, and to determine whether depot medroxyprogesterone acetate injection affects quality of life while waiting for surgery. STUDY DESIGN: This was a double-blind, randomized controlled trial of 400-mg depot medroxyprogesterone acetate injection or 0.9% saline injection at the preoperative visit. Patients with recent use of progesterone analogs were excluded. A sample size of 76 patients (38 per arm) was calculated to detect a 20% difference in decreased glandular cellularity between arms. Pathologic characteristics including the primary outcome, tumor glandular cellularity, from patients' diagnostic biopsies were reviewed by 2 dedicated gynecologic pathologists and compared to posttreatment hysterectomy specimens. On the night prior to surgery, patients completed the Functional Assessment of Cancer Therapy-Endometrial Survey (Version 4) to report quality of life while waiting for surgery. In comparing characteristics between the intervention and control groups, t tests were used for continuous variables, and χ2 or Fisher exact tests were used where appropriate for categorical data. RESULTS: From March 2015 through March 2016, 148 women were screened and 76 patients were enrolled. In all, 38 patients were randomized to and received depot medroxyprogesterone acetate injection and 38 were randomized to and received placebo injection. Demographics were similar between groups. Patients who received depot medroxyprogesterone acetate injection experienced a larger decrease in tumor glandular cellularity (mean change -64 [-31.8%] vs -14 [-5.5%] cells per quarter high-powered field in depot medroxyprogesterone acetate vs placebo groups, P = .002). This effect was most pronounced in women waiting ≥3 weeks for surgery. Several additional histologic and immunohistochemical markers of tumor differentiation and decreased cell proliferation were more pronounced in the depot medroxyprogesterone acetate group than in the placebo group. There were no significant differences in quality of life between groups on the Functional Assessment of Cancer Therapy-Endometrial Survey. Only 5.3% of patients who were approached declined to participate due to concerns regarding an intramuscular injection. CONCLUSION: Administration of depot medroxyprogesterone acetate prior to surgery for type I endometrial cancers caused greater tumor effect than placebo injection. Injection of depot medroxyprogesterone acetate was acceptable to and well tolerated by patients. Depot medroxyprogesterone acetate may represent a meaningful bridge to surgery in women who can expect long wait times.

Anal and Cervical High-Risk Human Papillomavirus Genotyping in Women With and Without Genital Neoplasia.

OBJECTIVE: The aim of the study was to compare the prevalence, genotypes, and rates of concomitant anal and cervical high-risk human papillomavirus (HR-HPV) in women with and without a history of HPV-related genital neoplasia. MATERIALS AND METHODS: This was a prospective cohort study conducted from December 2012 to February 2014. Women with a history of neoplasia were considered the high-risk group. Women without a history of neoplasia were considered the low-risk group. Cervical and anal cytology and HPV genotyping were performed. All women with abnormal anal cytology were referred for anoscopy. RESULTS: One hundred eighty-four women met inclusion criteria. High-risk HPV was detected in the anal canal of 17.4% of the high-risk group and 1.5% of the low-risk group (p = .003). High-risk HPV was detected in the cervix of 30.5% of the high-risk group and 7.6% of the low-risk group (p < .001). Concomitant anal and cervical high-risk HPV was detected in 4.4% of the high-risk group and was not detected in the low-risk group (p = .2). Among women with anal intraepithelial neoplasia 2 or greater (n = 5), 60% had HR-HPV detected in the anal canal while none had HR-HPV detected in the cervix. CONCLUSIONS: Women with a history of genital neoplasia are more likely to be positive for anal and cervical HR-HPV compared with women without a history of genital neoplasia. Although there was no significant difference in rates of concomitant HR-HPV between low- and high-risk groups, HR-HPV can be found concomitantly in the anus and the cervix and may be associated with anal intraepithelial neoplasia or carcinoma.

Understanding Women's Sexual Behaviors That May Put Them at Risk for Human Papillomavirus-Related Neoplasias: What Should We Ask?

OBJECTIVES: Human papillomavirus is a multifocal infection that can involve the cervix, vagina, vulva, anus, and oropharynx. Our study aimed to determine whether standard sexual history questions regarding anal intercourse identify women participating in anal-related sexual practices. MATERIALS AND METHODS: A cross-sectional survey was conducted at the dysplasia clinic of a large academic medical center. Women presenting with human papillomavirus-related cervical, vulvar, or vaginal abnormalities were eligible. Participants completed a self-administered sexual history questionnaire that included standard sexual history questions and more detailed questions about sexual practices. Additional demographic information was obtained from chart review. RESULTS: A total of 149 eligible women were approached, 125 (84%) consented and enrolled (ages = 21-65 years). Forty-seven (44%) reported participating in some type of anal-related sexual practice: anal fingering, oral-anal penetration, or anal intercourse. Of those participating in anal-related practices, 5 (11%) reported only anal fingering or oral-anal penetration. Thus, adding the new anal questions detected an additional 5% of women with high-risk anal behaviors that may have been missed by the standard question (p = .06). Seventy-nine women (63%) reported receiving oral penetration of the vagina, and 102 (82%) reported receiving vaginal fingering. Fifty-nine women (47%) used sex toys: 58 (98%) used sex toys vaginally, with 5 (8.5%) using them also anally. CONCLUSIONS: Women are willing to report their participation in a range of sexual practices. Of those who participated in anal practices, 11% did not have anal intercourse. Adding additional sexual health questions to clinical intake forms may enable clinicians to better counsel their patients on risky sexual behaviors.

Evaluation of anal cytology and dysplasia in women with a history of lower genital tract dysplasia and malignancy.

OBJECTIVE: To compare the prevalence of abnormal anal cytology, high-risk anal HPV and biopsy proven anal dysplasia among women with a history of lower genital tract malignancy compared to those with dysplasia. METHODS: A prospective cohort study was performed from December 2012 to February 2014 at outpatient clinics at an academic medical center. Women with a history of high-grade cervical, vulvar, or vaginal dysplasia, or malignancy were recruited. Anal cytology and HPV genotyping were performed. All women with abnormal anal cytology were referred for high-resolution anoscopy and biopsy. RESULTS: Sixty-seven women had a lower genital tract malignancy and 123 had a history of genital dysplasia. Average age in the malignancy group was 52.6years (range 27-86) versus 43.5years (range 21-81) in the dysplasia group (p<0.0002). Similar rates of anal dysplasia were seen in both groups, 12.99% (10 cases) in the malignancy group, versus 12.20% (15) in the dysplasia group (p=1.0). Six women in the malignancy group had anal intraepithelial neoplasia (AIN2+) compared to 2 in the dysplasia group (p=0.03). CONCLUSIONS: We found high rates of abnormal anal cytology and HPV in women with lower genital tract dysplasia and malignancy. We also found high rates of anal dysplasia in both groups with a trend towards increased rate in those women with history of genital malignancy. Since precancerous anal lesions are detectable and treatable, anal cancer screening may be potentially useful in both of these higher risk groups.

Endometrial Cancer Surgery With or Without Concomitant Stress Urinary Incontinence Surgery.

OBJECTIVE: To compare quality of life (QOL) among patients with endometrial intraepithelial neoplasia or early-stage endometrial cancer and stress urinary incontinence (SUI) who chose to have concomitant surgery with cancer surgery alone. METHODS: A multicenter, prospective cohort study was conducted across eight U.S. sites. Potentially eligible patients were screened for SUI symptoms. Those who screened positive were offered referral to urogynecology and incontinence treatment, including concomitant surgery. Participants were categorized into two groups: 1) concomitant cancer and SUI surgery or 2) cancer surgery alone. The primary outcome was cancer-related QOL as measured by the FACT-En (Functional Assessment of Cancer Therapy-Endometrial) (range 0-100; higher score indicates better QOL). The FACT-En and questionnaires assessing urinary symptom-specific severity and effects were assessed before surgery and 6 weeks, 6 months, and 12 months after surgery. Adjusted median regression accounting for clustering was used to examine the relationship between SUI treatment group and FACT-En scores. RESULTS: Of 1,322 (53.1%) patients, 702 screened positive for SUI with 532 analyzed; 110 (21%) chose concomitant cancer and SUI surgery, and 422 (79%) chose cancer surgery alone. FACT-En scores increased for both the concomitant SUI surgery and cancer surgery-only groups from the preoperative to the postoperative period. After adjustment for timepoint and preoperative covariates, the median change in FACT-En score (postoperative-preoperative) was 1.2 points higher (95% CI -1.3 to 3.6) for the concomitant SUI surgery group compared with the cancer surgery-only group across the postoperative period. Median time until surgery (22 days vs 16 days; P <.001), estimated blood loss (150 mL vs 72.5 mL; P <.001), and operative time (185.5 minutes vs 152 minutes; P <.001) were all greater for the concomitant cancer and SUI surgery group compared with the cancer-only group, respectively. CONCLUSION: Concomitant surgery did not result in improved QOL compared with cancer surgery alone for endometrial intraepithelial neoplasia and patients with early-stage endometrial cancer with SUI. However, FACT-En scores were improved in both groups.

Sensation of Pain Using Buffered Lidocaine for Infiltration Before Vulvar Biopsy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of buffered lidocaine on pain scores during vulvar biopsy. METHODS: We conducted a double-blind, randomized controlled trial, using prefilled, sequentially numbered, randomized syringes to infiltrate either 3 mL of buffered or nonbuffered lidocaine before vulvar biopsy. The primary outcome was a pain score marked on a 100-mm visual analog scale during infiltration. Secondary outcomes included pain scores after the procedure and change from baseline to infiltration. Participants were recruited to detect a clinically meaningful 15-mm difference in pain scores between groups. Sample size was calculated based on the null hypothesis that the mean pain score would be the same in women treated with buffered lidocaine as in those treated with nonbuffered placebo based on prior studies. Categorical data were compared by Fisher exact test, and continuous data were compared between groups by t-test or Wilcoxon rank sum test. RESULTS: From July 2015 to April 2018, 129 participants were randomized to one of two groups: nonbuffered lidocaine or buffered lidocaine. One hundred twenty-five were analyzed (nonbuffered n=62, buffered n=63). Four patients were excluded. The majority of participants were non-Hispanic white women with a mean age of 59 years. There was no difference in the primary outcome of pain during infiltration with a mean pain score of 35.8 mm in the buffered lidocaine group compared with 42.2 in the nonbuffered lidocaine group (mean difference -6.4; 95% CI -18.4 to 5.6; P=.3 by Wilcoxon rank sum test). There was also no difference in secondary outcomes of pain over the entire procedure (mean difference -0.3, 95% CI -9.7 to 9.2; P=.7) or change in pain from baseline to infiltration (mean difference -6.9, 95% CI -18.4 to 4.7; P=.2). CONCLUSION: There was no difference in pain scores during vulvar biopsy infiltration between the buffered and nonbuffered lidocaine groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02698527.

Anal Cytology and Human Papillomavirus Genotyping in Women With a History of Lower Genital Tract Neoplasia Compared With Low-Risk Women.

OBJECTIVE: To compare the prevalence of abnormal anal cytology and high-risk human papillomavirus (HPV) among women with a history of HPV-related genital neoplasia with women without a history of HPV-related genital neoplasia. METHODS: A cross-sectional cohort study was performed from December 2012 to February 2014. Women were recruited from outpatient clinics at an academic medical center. Women with a history of high-grade cervical, vulvar, or vaginal cytology, dysplasia, or cancer were considered the high-risk group. Women with no history of high-grade anogenital dysplasia or cancer were considered the low-risk group. Human immunodeficiency virus-positive women were excluded. Anal cytology and HPV genotyping were performed. Women with abnormal anal cytology were referred for high-resolution anoscopy. RESULTS: There were 190 women in the high-risk group and 83 in the low-risk group. The high-risk group was slightly older: 57 years compared with 47 years (P=.045); 21.7% of low-risk women had abnormal anal cytology compared with 41.2% of high-risk women (P=.006). High-risk HPV was detected in the anal canal of 1.2% of the low-risk group compared with 20.8% of the high-risk group (P<.001). Among women who underwent anoscopy, no anal dysplasia was detected in the low-risk group, whereas 13.4% in the high-risk group had anal dysplasia with 4.2% having anal intraepithelial neoplasia 2 or greater (P<.001). CONCLUSION: Human immunodeficiency virus-negative women with a history of lower genital tract neoplasia are more likely to have positive anal cytology, anal high-risk HPV, and anal intraepithelial neoplasia. Anal cancer screening should be considered for these high-risk women. LEVEL OF EVIDENCE: II.