The accuracy of colposcopic biopsy: analyses from the placebo arm of the Gardasil clinical trials.

We evaluated the overall agreement between colposcopically directed biopsies and the definitive excisional specimens within the context of three clinical trials. A total of 737 women aged 16-45 who had a cervical biopsy taken within 6 months before their definitive therapy were included. Per-protocol, colposcopists were to also obtain a representative cervical biopsy immediately before definitive therapy. Using adjudicated histological diagnoses, the initial biopsies and the same day biopsies were correlated with the surgically excised specimens. The overall agreement between the biopsies taken within 6 months of definitive therapy, and the definitive therapy diagnoses was 42% (weighted kappa = 0.34) (95% CI: 0.29-0.39). The overall underestimation of cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ (CIN2-3/AIS) and CIN3/AIS was 26 and 42%, respectively. When allowing for one degree of variance in the correlation, the overall agreement was 92% for CIN2-3/AIS. The overall agreement between the same day biopsy and definitive therapy specimen was 56% (weighted kappa = 0.41) (95% CI: 0.36-0.47), and the underestimation of CIN2-3/AIS was 57%. There were significant associations in the agreement between biopsies and excisional specimen diagnoses when patients were stratified by age, number of biopsies, lesion size, presence of human papillomavirus (HPV)16/18 and region. Of 178 diagnostic endocervical curettages performed, 14 (7.9%) found any HPV disease. Colposcopic accuracy improved when CIN2 and CIN3/AIS were grouped as a single predictive measure of high-grade disease. Colposcopy functioned well when allowed a one-degree difference between the biopsy and the surgical histologic interpretations, as done in clinical practice. Taking more than one biopsy improved colposcopic accuracy and could improve patient management.

Reasons for non-vaccination against HPV and future vaccination intentions among 19-26 year-old women.

BACKGROUND: Despite CDC recommendations regarding universal catch-up vaccination against human papillomavirus (HPV), only about ten percent of young adult women in the United States have been vaccinated. The purpose of this study was to better understand reasons for non-vaccination among insured 19-26 year-old women and to evaluate future vaccination intentions. METHODS: We used an administrative claims database from a large US managed care plan to identify women aged 19-26 for receipt of a mailed survey. From a sample of 1,375 women with no evidence of HPV vaccination from June 1, 2006 through April 30, 2007, 222 completed surveys were received, of which 185 were eligible for this analysis. The main outcome measures were unvaccinated women's attitudes and vaccine awareness, likelihood of future action regarding the vaccine, and reasons for inaction. RESULTS: Among the 185 non-vaccinees, 25.4% were married, 83.2% were white, and 89.2% had a college or higher level education. The vaccine was described as very important by 32.4% of subjects, and 30.1% had discussed the vaccine with a doctor and received a doctor's recommendation. Half or fewer of respondents were "very" or "extremely" likely to discuss the vaccine with their doctor (50.0%), do additional research on the vaccine (42.6%), ask a doctor to get the vaccine (37.5%), or make an appointment to get the vaccine (27.8%), while 48.0% were "somewhat", "very", or "extremely" likely to do nothing to get the vaccine. Among the latter, reasons for taking no action included being married or in a monogamous relationship (54.9%), belief that the vaccine is too new (35.4%), not having enough information about the vaccine (31.7%), concerns about side effects (24.4%), and uncertainty about insurance coverage (24.4%). CONCLUSIONS: Educational interventions may be needed to enhance HPV vaccination rates among 19-26 year-old women, particularly regarding information about vaccine safety, vaccine efficacy, insurance coverage, and the value of vaccination to women in monogamous relationships.

Experience of mismatch repair/microsatellite instability (MMR/MSI) testing among patients with advanced/metastatic colorectal cancer in the US.

Objective: We assessed knowledge and awareness of MMR/MSI testing among advanced/metastatic CRC patients in the US who had previously taken the test.Methods: A non-interventional, cross-sectional online survey was conducted among 150 US CRC patients invited through a research panel. Eligible patients had to be ≥18 years, with stage III or IV CRC (self-reported), had undergone MMR/MSI testing for CRC in past 12 months and could recall the test, and provided informed consent. Descriptive analyses were performed.Results: 81.3% of patients received MMR/MSI testing information from their doctor. Of 64.7% of patients who were a member of a patient support group, 86.6% received information from their groups. Most patients (82.7%) also searched for information on their own (internet searches). Most patients (93.5 to 96.9%) were satisfied with information received from these sources. Reasons for having testing done included increasing knowledge about their cancer (69.3%), being beneficial to determining treatment options (60.7%), and doctor recommendation (62.7%). Key barriers to testing included personal reservations regarding benefits of the test (29.3%), insurance coverage (27.3%), and out-of-pocket costs (18.7%); 45.3% reported no barriers.Conclusions: Patients were well informed about MMR/MSI testing. Increased education of testing benefits and addressing financial barriers may help to further improve testing rates.

Mismatch Repair/Microsatellite Instability Testing Practices among US Physicians Treating Patients with Advanced/Metastatic Colorectal Cancer.

The study objective was to assess US physicians' Mismatch Repair/Microsatellite Instability (MMR/MSI) testing practices for metastatic colorectal cancer (mCRC) patients. A non-interventional, cross-sectional online survey was conducted among 151 physicians (91 oncologists, 15 surgeons and 45 pathologists) treating mCRC patients in the US. Eligible physicians were US-based with at least 5 years of experience treating CRC patients, had at least one mCRC patient in their routine care in the past 6 months, and had ordered at least one MMR/MSI test for CRC in the past 6 months. Descriptive and logistic regression analyses were performed. Awareness of specific MMR/MSI testing guidelines was high (n = 127, 84.1%). Of those, 93.7% (119/127) physicians had awareness of specific published guidelines with majority 67.2% (80/119) being aware of National Comprehensive Cancer Network (NCCN) guidelines. Universal testing for all CRC patients was performed by 68.9% (104/151) physicians, while 29.8% (45/151) selectively order the test for some CRC patients. Key barriers for testing included insufficient tissue sample (48.3%, 73/151), patient declined to have the test done (35.8%, 54/151) and insurance cost concerns for patients (31.1%, 47/151), while 27.2% (41/151) reported no barriers. The survey demonstrated high awareness and compliance with MMR/MSI testing guidelines although universal testing rates seem to be suboptimal.

US Cancer Centers of Excellence Strategies for Increased Inclusion of Racial and Ethnic Minorities in Clinical Trials.

PURPOSE: Participation of racial and ethnic minority groups (REMGs) in cancer trials is disproportionately low despite a high prevalence of certain cancers in REMG populations. We aimed to identify notable practices used by leading US cancer centers that facilitate REMG participation in cancer trials. METHODS: The National Minority Quality Forum and Sustainable Healthy Communities Diverse Cancer Communities Working Group developed criteria by which to identify eligible US cancer centers-REMGs comprise 10% or more of the catchment area; a 10% to 50% yearly accrual rate of REMGs in cancer trials; and the presence of formal community outreach and diversity enrollment programs. Cancer center leaders were interviewed to ascertain notable practices that facilitate REMG accrual in clinical trials. RESULTS: Eight cancer centers that met the Communities Working Group criteria were invited to participate in in-depth interviews. Notable strategies for increased REMG accrual to cancer trials were reported across five broad themes: commitment and center leadership, investigator training and mentoring, community engagement, patient engagement, and operational practices. Specific notable practices included increased engagement of health care professionals, the presence of formal processes for obtaining REMG patient/caregiver input on research projects, and engagement of community groups to drive REMG participation. Centers also reported an increase in the allocation of resources to improving health disparities and increased dedication of research staff to REMG engagement. CONCLUSION: We have identified notable practices that facilitate increased participation of REMGs in cancer trials. Wide implementation of such strategies across cancer centers is essential to ensure that all populations benefit from advances in an era of increasingly personalized treatment of cancer.

Ectopic pregnancy in adolescents.

PURPOSE OF REVIEW: Ectopic pregnancy continues to be an important cause of morbidity and mortality in women. Tubal damage is the likely cause of ectopic pregnancy. Healthcare providers who care for adolescents must screen for and treat sexually transmitted diseases like Chlamydia in order to decrease the risk of tubal damage and ectopic pregnancy. Smoking is a risk factor for ectopic pregnancy and teens should be encouraged to never start smoking or to quit if they already do smoke. Though ectopic pregnancy is more likely to occur in adults, teens are at risk as well, and early diagnosis allows for the possibility of conservative management. RECENT FINDINGS: Any teen who presents with amenorrhea, pain, or vaginal bleeding should be evaluated for a possible ectopic pregnancy. Adolescents are more likely to present with pain than adults. Transvaginal ultrasound should be performed and if an intrauterine pregnancy or ectopic pregnancy is not clearly seen, correlation with serum beta-human chorionic gonadotropin levels is done. If the beta-human chorionic gonadotropin level is above the 'discriminatory zone' of 1500 mIU and the transvaginal ultrasound does not show an intrauterine pregnancy, ectopic pregnancy should be suspected. SUMMARY: Unruptured ectopic pregnancy may be treated with expectant management, surgical management, or medical management (methotrexate). Healthy teens with unruptured ectopic pregnancies and who are able and willing to undergo close surveillance may be treated with methotrexate. There are case reports of successful treatment of ectopic pregnancy with methotrexate in adolescents.

Risk factors for ectopic pregnancy: a comparison between adults and adolescent women.

PURPOSE: To compare the prevalence of classical risk factors and presenting signs and symptoms between adolescents and adults with ectopic pregnancy (EP). PROCEDURE: A database containing information regarding presentation symptoms, past medical history, and ultimate pregnancy outcomes of patients presenting to the Emergency Department during early pregnancy is maintained in our institution. Data were extracted and analyzed for all patients ultimately diagnosed with EP. Patients were separated into adult (> or =20 years of age) and adolescent groups (<20 years of age). Adjusted comparisons were made between these two groups regarding pain, vaginal bleeding, current and past pelvic infections, prior pregnancy history, and prior surgery using Pearson's chi-square, t test, and multivariable models. RESULTS: The incidence of EP was lower in the adolescent group versus the adult group (9.7% versus 21.7%). Classical risk factors such as prior EP (P < 0.01), and prior pelvic surgery (P < 0.01) were significantly more likely to be associated with adults than adolescents with EP. Adolescent patients were significantly more likely to present with abdominal pain (P = 0.045) and current gonorrhea and/or chlamydia (gc/ct) infection (P < 0.01). CONCLUSIONS: This preliminary study suggests that different risk factors may be associated with EP in adolescents compared to adults.

Premenstrual syndrome (PMS) in adolescents: severity and impairment.

OBJECTIVES: Identify the presence of patients with premenstrual syndrome (PMS) in an adolescent gynecology practice, and evaluate the reported severity, impairment and timing of the symptoms in the menstrual cycle. METHODS: Adolescents ages 13-18 years completed a symptom questionnaire, functional impairment ratings, and a brief medical history questionnaire during an office visit. Teens who responded that they had PMS and reported a premenstrual symptom score at least 50% greater than the postmenstrual score and rated moderate to severe impairment in one or more domains comprised the "PMS" group. Teens who responded that they had PMS but did not meet the symptom and impairment criteria were termed "PMS not supported." Teens who responded that they did not have PMS and did not meet the PMS symptom and impairment criteria were termed "No PMS." RESULTS: Study participants (n = 94) had a mean age of 16.5 years (+/-1.3 SD); 31% met the criteria for the PMS group, 54% said they had PMS but did not meet criteria, and 15% clearly had no PMS. In the PMS group, the most severe symptoms were mood swings, anxiety, and irritability, with the greatest impairment in the home/family domain. Dysmenorrhea and the duration of PMS were significantly associated (P < 0.01) with PMS in univariate and multivariate analyses. CONCLUSIONS: The reports of premenstrual symptoms, their severity, timing and impairment suggest that PMS is common in adolescents. Further study is warranted to confirm these results with prospective assessment of PMS and to evaluate treatments for adolescents who have clinically significant PMS.

An Overview of Quadrivalent Human Papillomavirus Vaccine Safety: 2006 to 2015.

BACKGROUND: A quadrivalent human papillomavirus (HPV4) type 6/11/16/18 vaccine (GARDASIL/SILGARD®) has been licensed in many countries around the world for the prevention of cervical, vulvar, vaginal, and anal cancers and precancers, as well as external genital warts causally related to HPV types 6/11/16/18. Across 7 phase 3 clinical trials involving more than 29,000 males and females ages 9-45 years, vaccination was generally well tolerated. Because of its expected public health benefit in reducing cervical cancer and other HPV-related diseases, the vaccine has been implemented in the national vaccination programs of several countries, with over 178 million doses distributed worldwide. METHODS: Extensive efforts to assess the safety of the vaccine in routine practice have been conducted over the past 9 years since licensure, including more than 15 studies in more than 1 million preadolescents, adolescents and adults from various countries. Most have been performed in the general population although there have been some in special populations (pregnant women, HIV-infected individuals and those with systemic lupus erythematosus). RESULTS: We present a summary of the published, postlicensure safety data from active and passive surveillance. Only syncope, and possibly skin infections were associated with vaccination in the postlicensure setting. Serious adverse events, such as adverse pregnancy outcomes, autoimmune diseases (including Guillain-Barre Syndrome and multiple sclerosis), anaphylaxis, venous thromboembolism and stroke, were extensively studied, and no increase in the incidence of these events was found compared with background rates. CONCLUSIONS: These results, along with the safety data from the prelicensure clinical trials, confirm that the HPV4 vaccine has a favorable safety profile. Key policy, medical and regulatory organizations around the world have independently reviewed these data and continue to recommend routine HPV vaccination.

Influence of patient's relationship status and HPV history on physicians' decisions to recommend HPV vaccination.

This study asked whether physicians would prioritize HPV vaccination on the basis of a young woman's relationship status and HPV history (i.e., abnormal Pap test, HPV infection or HPV-related disease). Eight hundred physicians identified as HPV vaccinators in a US claims database were surveyed. Prioritization was assessed on a 0-10 rating scale (from extremely low to extremely high priority). Physicians gave lower priority to vaccinating patients who were married or in a long-term monogamous relationship, with mean (SD) scores of 5.76 (2.82) and 6.80 (2.48), respectively, than for patients who were single and either dating or not dating, with mean (SD) scores of 9.8 (0.68) and 9.22 (1.61), respectively; p<.0001 for all pair-wise comparisons. Physicians did not differentially prioritize vaccination on the basis of previous HPV-related disease or abnormal Pap test. Despite epidemiologic evidence that women in long-term relationships remain at risk for HPV infection, physicians gave them lower priority for vaccination.