Adam K. Lewkowitz

Pooled Analysis of a Self-Sampling HPV DNA Test as a Cervical Cancer Primary Screening Method

Background Worldwide, one-seventh of cervical cancers occur in China, which lacks a national screening program. By evaluating the diagnostic accuracy of self-collected cervicovaginal specimens tested for human papillomavirus (HPV) DNA (Self-HPV testing) in China, we sought to determine whether Self-HPV testing may serve as a primary cervical cancer screening method in low-resource settings. Methods We compiled individual patient data from five population-based cervical cancer–screening studies in China. Participants (n = 13 140) received Self-HPV testing, physician-collected cervical specimens for HPV testing (Physician-HPV testing), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Screen-positive women underwent colposcopy and confirmatory biopsy. We analyzed the accuracies of pooled Self-HPV testing, Physician-HPV testing, VIA, and LBC to detect biopsy-confirmed cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and CIN3+. All statistical tests were two-sided. Results Of 13 004 women included in the analysis, 507 (3.9%) were diagnosed as CIN2+, 273 (2.1%) as CIN3+, and 37 (0.3%) with cervical cancer. Self-HPV testing had 86.2% sensitivity and 80.7% specificity for detecting CIN2+ and 86.1% sensitivity and 79.5% specificity for detecting CIN3+. VIA had statistically significantly lower sensitivity for detecting CIN2+ (50.3%) and CIN3+ (55.7%) and higher specificity for detecting CIN2+ (87.4%) and CIN3+ (86.9%) (all P values < .001) than Self-HPV testing, LBC had lower sensitivity for detecting CIN2+ (80.7%, P = .015), similar sensitivity for detecting CIN3+ (89.0%, P = .341), and higher specificity for detecting CIN2+ (94.0%, P < .001) and CIN3+ (92.8%, P < .001) than Self-HPV testing. Physician-HPV testing was more sensitive for detecting CIN2+ (97.0%) and CIN3+ (97.8%) but similarly specific for detecting CIN2+ (82.7%) and CIN3+ (81.3%) (all P values <.001) than Self-HPV testing. Conclusions The sensitivity of Self-HPV testing compared favorably with that of LBC and was superior to the sensitivity of VIA. Self-HPV testing may complement current screening programs by increasing population coverage in settings that do not have easy access to comprehensive cytology-based screening.

Prevalence of human papillomavirus and cervical intraepithelial neoplasia in China: a pooled analysis of 17 population-based studies.

High‐risk (HR) human papillomavirus (HPV) prevalence has been shown to correlate well with cervical cancer incidence rates. Our study aimed to estimate the prevalence of HR‐HPV and cervical intraepithelial neoplasia (CIN) in China and indirectly informs on the cervical cancer burden in the country. A total of 30,207 women from 17 population‐based studies throughout China were included. All women received HPV DNA testing (HC2, Qiagen, Gaithersburg, MD), visual inspection with acetic acid and liquid‐based cytology. Women positive for any test received colposcopy‐directed or four‐quadrant biopsies. A total of 29,579 women had HR‐HPV testing results, of whom 28,761 had biopsy confirmed (9,019, 31.4%) or assumed (19,742, 68.6%) final diagnosis. Overall crude HR‐HPV prevalence was 17.7%. HR‐HPV prevalence was similar in rural and urban areas but showed dips in different age groups: at age 25–29 (11.3%) in rural and at age 35–39 (11.3%) in urban women. In rural and urban women, age‐standardized CIN2 prevalence was 1.5% [95% confidence interval (CI): 1.4–1.6%] and 0.7% (95% CI: 0.7–0.8%) and CIN3+ prevalence was 1.2% (95% CI: 1.2–1.3%) and 0.6% (95% CI: 0.5–0.7%), respectively. Prevalence of CIN3+ as a percentage of either all women or HR‐HPV‐positive women steadily increased with age, peaking in 45‐ to 49‐year‐old women. High prevalence of HR‐HPV and CIN3+ was detected in both rural and urban China. The steady rise of CIN3+ up to the age group of 45–49 is attributable to lack of lesion removal through screening. Our findings document the inadequacy of current screening in China while indirectly raising the possibility that the cervical cancer burden in China is underreported.

Prevalence of HPV Infection And Cervical Intraepithelial Neoplasia And Attitudes towards HPV Vaccination among Chinese Women Aged 18-25 in Jiangsu Province

ObjectiveFew data are available on the epidemiology of HPV and cervical cancer among Chinese women younger than 25 years old. This study aimed to estimate the HPV infection rate and the prevalence of cervical intraepithelial neoplasia (CIN) in women aged 18–25, as well as their knowledge of and attitudes towards HPV vaccination.MethodsA population-based cervical cancer screening study was conducted on women aged 18–25 in Jiangsu province in 2008. Participants provided socio-demographic, reproductive and behavioral information and completed a survey about their knowledge of and attitudes towards HPV vaccination. Women then underwent a gynecologic exam to provide two cervical exfoliated cell samples for high risk HPV DNA testing and liquid-based cytology (LBC) as well as visual inspection with acetic acid (VIA). Women testing positive for any test were referred to colposcopy and biopsy. The gold standard for diagnosis of cervical lesions was directed or random biopsies.ResultsWithin the sample of 316 women, 3.4% of them were diagnosed with CIN grade 2 or worse lesions and 17.1% were found to be positive for HPV DNA. Among these young women, extra-marital sexual behavior of them (OR=2.0, 95%CI: 1.1–3.8) or their husbands (OR=2.6, 95%: 1.4–4.7) were associated with an increased risk of HPV positivity. Although overall HPV awareness was low, after a brief educational intervention, 98.4% reported they would electively receive HPV vaccination and would also recommend that their daughters be vaccinated. However, most urban and rural women reported their ideal maximum out-of-pocket contribution for HPV vaccination to be less than 500 RMB and 50–100 RMB, respectively.ConclusionOur study indicates cervical disease burden is relatively high among sampled Chinese women aged 18–25. Appropriate educational interventions for female adolescents and strategies to subsidize vaccine costs are definitely needed to ensure the effectiveness of vaccination campaigns in China.

Barriers to conceiving sibling donors for sickle cell disease: perspectives from patients and parents

Objectives. The lack of matched sibling donors poses a significant barrier to utilizing hematopoietic cell transplantation (HCT), the only proven cure for children with sickle cell disease (SCD). Little is known about current patient and parent perspectives towards HCT for SCD. This study examines the perceived barriers of transplant, and the use of in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD), when there is no pre-existing sibling donor. Design. Semi-structured interviews were conducted with adult patients with SCD and parents of children with SCD in an urban medical center in the US. Transcribed data was analyzed using qualitative methods. Results. Of 23 participants, 17 reported having heard of HCT for SCD. Fewer knew of IVF or PGD as a means for conceiving an unaffected child (n =7) or to select a potential umbilical cord blood donor (n =1). The financial cost of IVF and PGD was perceived as a significant initial barrier to accessing these technologies, with the clinical risks of HCT and the ethical appropriateness of using PGD also identified as barriers. The value of informing families of these options was a recurring theme, even among respondents who personally disagreed with their application. Conclusion. The low utilization of curative strategies for SCD appears to be partly attributable to a lack of information about the technologies available to facilitate transplantation. Ethical reservations, while present, were not static and did not preclude patients’ and parents’ desire to be informed. We discuss the implications of these perceived barriers to the dissemination of advanced medical technologies for SCD.

Population-based human papillomavirus 16, 18, 6 and 11 DNA positivity and seropositivity in Chinese women.

To optimize HPV vaccination implementation at the population‐level in China, data are needed on age‐specific HPV 16, 18, 6 and 11 prevalence. This cross‐sectional, population‐based study evaluated the age‐ and type‐specific HPV 16, 18, 6 and 11 prevalence of DNA and serum antibodies among women in China. From July 2006 to April 2007, 17–54 year old women from three rural provinces (Xinjiang, Shanxi and Henan) and two cities (Beijing and Shanghai) provided cervical exfoliated cells for HPV DNA and liquid‐based cervical cytology (SurePath). High‐ and low‐risk HPV types were detected with HC‐II (Qiagen), with genotyping of HPV‐positive samples using Linear Array (Roche). HPV 16, 18, 6 and 11 serum antibodies were detected using a Luminex‐based, competitive immunoassay (Merck). A total of 4,206 women with DNA and serum antibody results were included. HPV 16 DNA prevalence peaked in women aged 30–34 (4.2%) and 45–49 yr (3.8%), while HPV 18 DNA prevalence peaked at ages 40–44 yr (1.3%). Most women were dually DNA and serum antibody negative: HPV 16 (92.2%), 18 (97.2%), HPV 16 and 18 (90.2%), 6 (92.0%), 11 (96.6%), 6 and 11(89.9%) and HPV 16, 18, 6 and 11 (82.5%). Future national HPV vaccination programs in China should target younger women due to increased exposure to HPV types 16, 18, 6 and 11 with increasing age. Cumulative exposure of HPV may be underreported in this population, as cross‐sectional data do not accurately reflect exposure to HPV infections over time.

Examining pregnancy-specific smartphone applications: what are patients being told?

Objective:The objective of this study is to evaluate the informative content of two free, pregnancy-specific smartphone applications and their accuracy and adherence to prenatal care guidelines.Study Design:This is a qualitative analysis of the information delivered through two free, pregnancy-specific smartphone applications (apps): Text4Baby (T4B) and Baby Center’s ‘My Pregnancy Today’ (BC). All information from conception through 2 weeks postpartum were transcribed and coded independently by two physician researchers. Content was analyzed and assigned thematic codes. The proportion of content each app delivered per theme was then calculated and the χ2-test was used to compare thematic frequency between apps.Results:A total of 609 pieces of daily content were transcribed; 698 message themes were coded and analyzed. Most information delivered by T4B was about fetal development (23.8%) or prenatal care (16.6%); most content from BC was about normal pregnancy symptoms (20.1%) or maternal well-being (21.1%); the differences between apps for each of these themes were statistically significant (P<0.05). A total of four messages contained incomplete or ambiguous content; neither app delivered overtly incorrect medical information. T4B and BC had a similar proportion of information that was in-line with the American College of Obstetrics and Gynecology Guidelines for Prenatal Care. Neither app delivered any messages about contraception.Conclusion:T4B and BC are free, pregnancy-specific apps with different focuses. Neither app delivers comprehensive prenatal information, as evidenced by the absence of information about postpartum contraception. More information is needed to determine the role of such apps in prenatal care.

Effect of stage of initial labor dystocia on vaginal birth after cesarean success

OBJECTIVE The objective of the study was to examine whether the stage of labor dystocia causing a primary cesarean delivery (CD) affects a trial of labor after cesarean (TOLAC) success. STUDY DESIGN This was a retrospective cohort study of women who had primary CD of singleton pregnancies for first- or second-stage labor dystocia and attempted TOLAC at a single hospital between 2002 and 2014. We compared TOLAC success rates between women whose primary CD was for first- vs second-stage labor dystocia and investigated whether the effect of prior dystocia stage on TOLAC success was modified by previous vaginal delivery (VD). RESULTS A total of 238 women were included; nearly half (49%) achieved vaginal birth after cesarean (VBAC). Women with a history of second-stage labor dystocia were more likely to have VBAC compared with those with first-stage dystocia, although this trend was not statistically significant among the general population (55% vs 45%, adjusted odds ratio, 1.4, 95% confidence interval, 0.8-2.5]). However, among women without a prior VD, those with a history of second-stage dystocia did have statistically higher odds of achieving VBAC than those with prior first-stage dystocia (54% vs 38%, adjusted odds ratio, 1.8 [95% confidence interval, 1.0-3.3], P for interaction = .043). CONCLUSION Nearly half of women with a history of primary CD for labor dystocia will achieve VBAC. Women with a history of second-stage labor dystocia have a slightly higher VBAC rate, seen to a statistically significant degree in those without a history of prior VD. TOLAC should be offered to all eligible women and should not be discouraged in women with a prior second-stage arrest.

Social media messaging in pregnancy: comparing content of Text4baby to content of free smart phone applications of pregnancy

Abstract Objective: Text4baby is the only free text-message program for pregnancy available. Our objective was to determine whether content differed between Text4baby and popular pregnancy smart phone applications (apps). Methods: Researchers enrolled in Text4baby in 2012 and downloaded the four most-popular free pregnancy smart phone apps in July 2013; content was re-extracted in February 2014. Messages were assigned thematic codes. Two researchers coded messages independently before reviewing all the codes jointly to ensure consistency. Logistic regression modeling determined statistical differences between Text4baby and smart phone apps. Results: About 1399 messages were delivered. Of these, 333 messages had content related to more than one theme and were coded as such, resulting in 1820 codes analyzed. Compared to smart phone apps, Text4baby was significantly more likely to have content regarding Postpartum Planning, Seeking Care, Recruitment and Prevention and significantly less likely to mention Normal Pregnancy Symptoms. No messaging program included content regarding postpartum contraception. Conclusions: To improve content without increasing text message number, Text4baby could replace messages on recruitment with messages regarding normal pregnancy symptoms, fetal development and postpartum contraception.

Does an Electronic Health Record Improve Completeness of Prenatal Studies

OBJECTIVE To determine whether implementation of an electronic health record (EHR) would increase the rate of prenatal Human Immunodeficiency Virus (HIV) and purified protein derivative (PPD) testing. METHODS Eligible participants received prenatal care and delivered at term at a single academic institution in March-April 2011, March-April 2012, and March-April 2013. As part of routine prenatal care, all women were tested for HIV and tuberculosis (via a PPD test) during each pregnancy. The 2011 cohort was charted on paper. The 2012 and 2013 cohorts were charted via EHR. To appear in the prenatal labs display in EHR, PPD results must be manually documented, while HIV results are uploaded automatically. Documentation of PPD and HIV tests were analyzed. RESULTS The 2011, 2012, and 2013 cohorts had 249, 208, and 190 patients, respectively. Complete PPD and HIV results were less likely to be charted in the 2012 EHR cohort compared to the paper chart cohort (72.1% vs. 80.1%; p=0.03). This was driven by fewer documented completed PPD tests (2011 83.9% vs. 2012 72.6%; p=0.003). PPD test documentation improved non-significantly to 86.2% in the 2013 EHR cohort (p=0.5). HIV documentation rates increased from 95.2% in the paper chart cohort to 98.6% in the 2012 EHR cohort (p=0.04), and to 98.9% in the 2013 EHR cohort (p=0.03). CONCLUSIONS EHR implementation corresponded with a marked decrease in documentation of PPD test completion. HIV documentation rates improved. PPD results were likely charted incorrectly in provider notes due to training deficiencies and lack of standardization, which did not improve significantly after retraining.

Sociodemographic and attitudinal predictors of simultaneous and redundant multiple marker and cell-free DNA screening among women aged 35 years

Objective:To identify characteristics associated with undergoing cell-free DNA (cfDNA) and multiple marker screening (MMS) simultaneously or redundantly (after receiving negative results from the first screening test) among women aged ⩾35 years.Study design:Participants presenting for prenatal testing completed a questionnaire that included measures of pregnancy worry and attitudes toward potential testing outcomes; data on prenatal test use was obtained via medical record review. We used multivariable logistic regression to identify factors associated with redundant or simultaneous screening.Results:Among 164 participants, 69 (42.1%) had cfDNA redundantly (n=51) to, or simultaneously (n=18) with, MMS. Compared with the 46 MMS-negative women who did not undergo further testing, those who underwent redundant or simultaneous cfDNA/MMS screening were more likely to have annual family incomes >