Intimate Partner Violence and Cervical Neoplasia

Intimate partner violence (IPV) is associated with a range of adverse physical health outcomes, including chronic and infectious diseases. An emerging literature suggests that partner violence and specifically sexual violence may be associated with an increased risk of cervical neoplasia. To assess the risk of preinvasive and invasive cervical cancer in a cross-sectional study of women screened for IPV by type, frequency and duration, 1152 women ages 18–65 were recruited from family practice clinics in 1997–1998. They were screened for IPV during a brief in-clinic interview, and health history and current status were assessed in a follow-up interview. Of 1152 women surveyed, 14 (1.2%) reported cervical cancer, and 20.3% (n 5 234) reported treatment for cervical neoplasia. Ever experiencing IPV was associated with an increased risk of invasive cervical cancer (adjusted relative risk [aRR] 5 4.28; 95% CI 1.94, 18.39) and with preinvasive cervical neoplasia (aRR 5 1.47; 95% CI 1.16, 1.82). This association was stronger for women experiencing physical or sexual IPV than for women experiencing psychological IPV. Women with cervical cancer reported being in violent relationships longer and experiencing more frequent physical and sexual assaults and more IPV-associated injuries than did controls. This exploratory study suggests that IPV may increase a woman’s risk of cervical neoplasia. The mechanism by which IPV affects cervical neoplasia may be indirect through psychosocial stress or negative coping behaviors or direct through sexual assaults and transmission of human papillomavirus (HPV)

Hormonal and Barrier Methods of Contraception, Oncogenic Human Papillomaviruses, and Cervical Squamous Intraepithelial Lesion Development

We assessed the influence of hormonal (oral, injectable, or levonorgestrel [Norplant, Wyeth-Ayerst, Philadelphia, PA]) and barrier methods of contraception on the risk of cervical squamous intraepithelial lesions (SIL), while adjusting for high-risk (HR) HPV infection. Subjects were women receiving family planning services through the state health department clinics from 1995 to 1998. We selected 60 cases with high-grade cervical/SIL (HSIL) and 316 with low-grade cervical/SIL (LSIL) and controls (427 women with normal cervical cytology) and analyzed cervical DNA for HR-HPV, using Hybrid Capture I (Digene; Gaithersburg, MD).When assessing ever use, duration, recency, latency, and age at first use, neither oral contraceptives (OC), Norplant, nor injectable use was associated with an increased risk of SIL development after adjusting for age, age at first sexual intercourse, and HR-HPV positivity. Among HR-HPV-positive women, longer duration barrier method use was associated with a reduced risk of SIL. This finding has important clinical implications for SIL prevention among HR-HPV-infected women

Psychosocial Stress and Cervical Neoplasia Risk

OBJECTIVE: We assessed the association between psychosocial stress and preinvasive cervical neoplasia development controlling for HR-HPV infection. METHODS: This case-control study enrolled low-income women receiving family planning services at health department clinics. There were 59 cases with biopsy confirmed HSIL and 163 with low-grade SIL and 160 controls with normal cervical cytology. A modified SLE scale was used to measure stressful events and the perceived impact of the event in the prior 5 years. Unconditional logistic regression was used to assess SIL risk and stressful events scores and by subscales. RESULTS: After adjusting for age, HR-HPV infection, and lifetime number of sex partners, the SLE count score was associated with an increased risk of SIL among white women (aOR = 1.20; 95% CI = 1.04, 1.38) yet not among African American women (aOR = 1.02; 95% CI = 0.87, 1.19). The relationship stress subscale (divorce, infidelity, an increase in the number of arguments, and psychological and physical partner violence) was the only one of four subscales (loss, violence, and financial stress) associated with SIL, again, only among white women (aOR = 1.54; 95% CI = 1.21, 1.96). CONCLUSIONS: These data suggest that psychosocial stress may play a role in SIL development. Future studies are needed to confirm these findings, to explore racial difference in reporting stress, and to explore the mechanism through which psychosocial stress may affect cervical neoplasia risk

Retinoic Acid Resistance at Late Stages of Human Papillomavirus Type 16-Mediated Transformation of Human Keratinocytes Arises Despite Intact Retinoid Signaling and Is Due to a Loss of Sensitivity to Transforming Growth Factor-β

AbstractIn our in vitro model of human cell carcinogenesis, normal human foreskin keratinocytes (HKc) transfected with human papillomavirus type 16 DNA (HKc/HPV16) progress toward malignancy through several phenotypically defined and reproducible “steps” that include immortalization, growth factor independence (HKc/GFI), differentiation resistance (HKc/DR), and ultimately malignant conversion. While HKc/HPV16 are very sensitive to growth inhibition by all-trans-retinoic acid (RA) at early passages, they lose their sensitivity to RA during progression in culture. However, gel mobility shift assays using the retinoid response elements DR1 and DR5 showed no changes in binding activity of nuclear extracts obtained from HKc/HPV16 at different stages of in vitro progression. Similarly, Western blot analyses for retinoic acid receptor γ-1 and the retinoid X receptors failed to reveal any decreases in the levels of these retinoid receptors throughout progression. In addition, luciferase activity driven by the SV40 promoter with a DR5 enhancer element was activated following RA treatment of HKc/DR that were resistant to growth inhibition by RA. Since RA induces transforming growth factor-β2 (TGF-β2) in normal HKc and HKc/HPV16, we investigated whether this response changed during progression. Again, RA induced TGF-β2 mRNA in early and late passage HKc/HPV16, HKc/GFI, and HKc/DR approximately to the same extent, confirming that the RA signaling pathways remained intact during in vitro progression despite the fact that the cells become resistant to growth inhibition by RA. We then investigated the sensitivity of HKc/HPV16 to growth inhibition by TGF-β. While early passage HKc/HPV16 were as sensitive as normal HKc to growth inhibition by TGF-β1 and TGF-β2, the cells became increasingly resistant to both TGF-β isotypes during in vitro progression. In addition, while both RA and TGF-β produced a decrease in the levels of mRNA for the HPV16 oncogenes E6 and E7 in early passage HKc/HPV16, this effect was also lost at later stages of progression. Finally, blocking anti-TGF-β antibodies partially prevented RA inhibition of growth and E6/E7 expression in early passage HKc/HPV16. Taken together, these data strongly suggest that inhibition of growth and HPV16 early gene expression in HKc/HPV16 by RA is mediated by TGF-β and that a loss of RA sensitivity is linked to TGF-β resistance rather than alterations in RA signaling

2017 GJMPP Monograph Series: Grace Jordan McFadden Professors Program

The Grace Jordan McFadden Professors Program (GJMPP), formerly the African American Professors Program (AAPP)/Carolina Diversity Professors Program (CDPP) at the University of South Carolina, is honored to publish its sixteenth edition of this annual monograph series. AAPP recognizes the significance of offering its scholars a venue through which to engage actively in research and to publish their refereed papers that continually contribute to their respective fields of study. Parallel with the publication of their manuscripts is the opportunity to gain visibility among colleagues throughout postsecondary institutions at national and international levels. Scholars who have contributed papers for this monograph are acknowledged for embracing the value of including this responsibility within their academic milieu. Writing across disciplines adds broadly to the intellectual diversity of these manuscripts. From neophytes to quite experienced individuals, the chapters have been researched and written in depth. Founded in 1997 through the Department of Educational Leadership and Policies in the College of Education, AAPP was designed originally to address the under-representation of African American professors on college and university campuses. Its mission is to expand the pool of these professors in critical academic and research areas. Sponsored historically by the University of South Carolina, the W. K. Kellogg Foundation, and the South Carolina General Assembly, the program recruits doctoral students for disciplines in which African Americans currently are underrepresented among faculty in higher education. The continuation of this monograph series is seen as responding to a window of opportunity to be sensitive to an academic expectation of graduates as they pursue career placement and, at the same time, to allow for the dissemination of products of scholarship to a broader community. The importance of this series has been voiced by one of our 2002 AAPP graduates, Dr. Shundelle LaTjuan Dogan, formerly an Administrative Fellow at Harvard University, a Program Officer for the Southern Education Foundation, and a Program Officer for the Arthur M. Blank Foundation in Atlanta, Georgia. She is currently a Corporate Citizenship and Corporate Affairs Manager for IBM-International Business Machines in Atlanta, Georgia and has written an impressive Foreword for the 2014 monograph. Dr. Dogan wrote: “One thing in particular that I want to thank you for is having the African American Professors Program scholars publish articles for the monograph. I have to admit that writing the articles seemed like extra work at the time. However, in my recent interview process, organizations have asked me for samples of my writing. Including an article from a published monograph helped to make my portfolio much more impressive. You were ‘right on target’ in having us do the monograph series” (AAPP 2003 Monograph, p. xi). The Grace Jordan McFadden Professors Program purports to advance the tradition of spearheading international scholarship in higher education as evidenced through inspiration from this group of interdisciplinary manuscripts. I hope that you will envision these published papers for serving as an invaluable contribution to your own professional and career enhancement. John McFadden, PhD The Benjamin Elijah Mays Distinguished Professor Emeritus Director, Grace Jordan McFadden Professors Program University of South Carolina Columbia, South Carolinahttps://scholarcommons.sc.edu/mcfadden_monographs/1004/thumbnail.jp

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin