Comparison of Overall Sensitivity and Specificity across Different Newborn Screening Algorithms for Congenital Cytomegalovirus

Screening newborns for congenital cytomegalovirus (cCMV) infection is critical for early detection and prompt diagnosis of related long-term consequences of infection, such as sensorineural hearing loss and neurodevelopmental delays. The objective of this study was to describe the validity of different newborn cCMV infection screening approaches and compare the expected number of cCMV cases detected across targeted and universal screening algorithms. The overall sensitivity (OSn) of targeted screening algorithms that required failure of auditory brain stem response and transient evoked otoacoustic emissions (TOAE; two-fail serial testing) or TOAE only (one-fail serial testing) before diagnostic CMV testing using saliva and urine PCR tests was 79% and 88%, respectively. The OSn for two-fail serial testing with diagnostic CMV testing using dried blood spot (DBS) was 75%. In contrast, OSn was 90% for universal screening (saliva and urine PCR tests) and 86% for universal screening with DBS testing alone. Overall, specificities were 100% across all algorithms. Universal screening using DBS testing and universal screening using saliva and urine testing can potentially detect 312 and 373 more cCMV cases per 100,000 live births, respectively, than two-fail serial testing. Overall, implementing universal cCMV newborn screening would improve cCMV detection, ultimately leading to better health outcomes

A Qualitative Assessment of Clinical Practice Guidelines and Patterns for Congenital Cytomegalovirus in the United States

Cytomegalovirus (CMV) infection during pregnancy may result in long-term health problems for children with congenital CMV (cCMV). Currently, no prevention or treatment interventions are approved by the Food and Drug Administration for a cCMV indication. Healthcare provider and public awareness is low, and formal clinical practice guidelines and local practice patterns vary. A pilot study of eight cCMV experts was performed using qualitative semi-structured interviews to better understand clinical practice guidelines and patterns in the United States. Results from participant interviews highlighted the need for better prenatal diagnostic techniques, broader neonatal screening opportunities, and more robust evidence supporting intervention strategies. Healthcare provider and public partnerships are essential for advancing cCMV guidelines and improving care delivery. Our results provide a preliminary knowledge base and framework for developing a consensus cCMV research agenda to address evidence gaps that limit the revision of clinical practice guidelines. The changes in clinical practice patterns that may arise as a result of further research have the potential to reduce risk during pregnancy and improve care for children with cCMV infection

Condylomata acuminata (anogenital warts) contain accumulations of HIV-1 target cells that may provide portals for HIV transmission

Background: Condylomata acuminata [anogenital warts (AGW)] are prevalent in HIV-infected individuals and sexually active populations at risk for HIV acquisition, and have been associated with HIV transmission. We compared AGW to control tissue for abundance, types and location of HIV-target cells, and for susceptibility to HIV infection in vitro, to provide biological evidence that AGW facilitate HIV transmission. Methods: We used immunohistology to identify HIV-target cells in AGW and control skin. We also inoculated AGW and control tissue from HIV-negative men with HIV in vitro, and assessed infection by TZM-bl and p24 assays. Results: CD1a+ dendritic cells, CD4+ T cells and macrophages were significantly more abundant in the epidermis of AGW than control tissue. These HIV target cells also often appeared in large focal accumulations in the dermis of AGW. Two out of 8 AGW vs. 0 of 8 control tissues showed robust infection with HIV in vitro. Conclusions: Compared to normal skin, AGW contain significantly higher concentrations of HIV-target cells that may be susceptible to HIV infection. Condylomata may thus promote HIV transmission, especially in the setting of typical lesion vascularity and friability. Prevention or treatment of AGW may decrease the sexual transmission of HIV

Facilitators of and barriers to HPV vaccination among sexual and gender minority patients at a Boston community health center

•Knowledge, beliefs, engagement, and fear impact HPV vaccination among sexual and gender minorities.•Providers’ HPV knowledge and affirmation of sexual and gender minorities enable HPV vaccination.•Inclusive healthcare settings, marketing, and public health campaigns may help HPV vaccination. Young sexual minority individuals have lower human papillomavirus (HPV) vaccine completion rates than the general population, and little is known about how gender minority people perceive HPV vaccination. The aim of this study was to qualitatively identify patient-, provider-, and systems-level barriers and facilitators for HPV vaccination among sexual and gender minority (SGM) people. Fifteen SGM-identified individuals, ages 23–26, were recruited at an urban community health center in Boston, MA, that specializes in care for SGM. Participants were enrolled in a study that utilized surveys and in-person focus groups. During focus groups, participants were asked to describe their perceived barriers and facilitators for completion of HPV vaccination. Fourteen participants reported having a sexual minority identity, and five participants reported having a gender minority identity. Participants described the following factors influencing HPV vaccination: (1) at the patient level, low HPV-related knowledge and lack of engagement in care were associated with less vaccination, whereas fear of HPV-related disease motivated vaccination; (2) at the provider level, knowledge and SGM cultural-competence related to HPV was associated with patient willingness to be vaccinated; (3) at the systems level, SGM identity-affirming healthcare settings were associated with increased vaccination, whereas historical trends in HPV vaccine marketing selectively for cisgender women and lack of public awareness of HPV-related disease among SGM were associated with decreased vaccincation. Our study identified internal and external barriers for HPV vaccination related among SGM patients. These findings highlight the need to increase public awareness about the risks of HPV-related disease among SGM and educate SGM youth about HPV-related disease and vaccine importance. Finally, this study supports the need for future interventions to cultivate SGM-competent providers and SGM identity-affirming healthcare settings as a way to increase HPV vaccination

Facilitators of and barriers to high-resolution anoscopy adherence among men who have sex with men: a qualitative study

Background Anal cancer is a rare malignancy that disproportionately affects men who have sex with men (MSM) and HIV-infected people. Anal cancer is associated with human papillomavirus (HPV) in upward of 90% of cases and is preceded by pre-cancerous changes in cells of the anal canal. High-resolution anoscopy (HRA) is used for the detection, treatment and continued monitoring of anal dysplasia. Practice guidelines regarding anal cancer prevention vary by jurisdiction and institution, and patient engagement is low for high-risk populations such as MSM. The purpose of this study is to characterise perceptions among MSM of barriers to and facilitators of their adherence to HRA follow-up recommendations. Surveys and in-person focus groups with MSM who were either adherent or non-adherent to HRA follow-up recommendations at a Federally Qualified Health Centre in Boston, MA, which specialises in sexual and gender minority care, were conducted. Facilitators of and barriers to follow-up were identified by deductive content analysis. Focus group participants identified the following barriers to and facilitators of HRA follow up: (1) patient-level beliefs about HPV-related disease or HRA, ability to engage in care, internalised stigma and physical discomfort; (2) provider-level knowledge and expertise, communication skills and relationship-building with patient; and (3) systems-level societal stigma and healthcare system inefficiencies. Reinforcing facilitators of and reducing barriers to HRA follow up may improve adherence among MSM. This includes improvements to: patient education, provider training to increase knowledge and cultural sensitivity, public awareness about HPV-related anal cancer, physical discomfort associated with HRA and systems inefficiencies

Safety and efficacy of topical cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women.

ObjectiveTo evaluate the safety and efficacy of topical cidofovir for treatment of high-grade squamous perianal intraepithelial neoplasia (PAIN) and vulvar intraepithelial neoplasia (VIN) lesions in HIV-positive individuals.DesignPhase IIa prospective multicenter trial conducted at eight clinical sites through the AIDS Malignancy Consortium.Methods: HIV-positive patients with biopsy-proven high-grade PAIN that was at least 3 cm were enrolled. PAIN biopsy specimens were assessed for human papillomavirus (HPV) using PCR and type-specific HPV probing. Participants applied 1% topical cidofovir to PAIN and VIN (if present) for six 2-week cycles. Results were designated as complete response (CR), partial response (PR) (>50% reduction in size), stable disease, or progressive disease (PD).ResultsTwenty-four men and nine women (eight with high-grade VIN as well) were enrolled. Mean age was 44 years and mean CD4 cell count was 412 cells/μl. HPV DNA (most commonly HPV16) was detected in all pretreatment study specimens. Twenty six (79%) participants completed treatment per protocol: CR, five (15%); PR, 12 (36%), stable disease, seven (21%); PD, two (6%) (one with a superficially invasive cancer and one with new area of high-grade PAIN). Treatment was well tolerated with most common adverse events being mild to moderate affecting lesional skin: pain/burning/irritation (25 patients) and ulceration (13 patients).ConclusionTopical cidofovir had 51% efficacy in the short-term treatment of high-grade PAIN and VIN with acceptable toxicity in HIV-positive individuals. Randomized control studies with more prolonged treatment courses and longer follow-up to assess the durability of the response are needed

Safety and efficacy of topical cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women.

ObjectiveTo evaluate the safety and efficacy of topical cidofovir for treatment of high-grade squamous perianal intraepithelial neoplasia (PAIN) and vulvar intraepithelial neoplasia (VIN) lesions in HIV-positive individuals.DesignPhase IIa prospective multicenter trial conducted at eight clinical sites through the AIDS Malignancy Consortium.Methods: HIV-positive patients with biopsy-proven high-grade PAIN that was at least 3 cm were enrolled. PAIN biopsy specimens were assessed for human papillomavirus (HPV) using PCR and type-specific HPV probing. Participants applied 1% topical cidofovir to PAIN and VIN (if present) for six 2-week cycles. Results were designated as complete response (CR), partial response (PR) (>50% reduction in size), stable disease, or progressive disease (PD).ResultsTwenty-four men and nine women (eight with high-grade VIN as well) were enrolled. Mean age was 44 years and mean CD4 cell count was 412 cells/μl. HPV DNA (most commonly HPV16) was detected in all pretreatment study specimens. Twenty six (79%) participants completed treatment per protocol: CR, five (15%); PR, 12 (36%), stable disease, seven (21%); PD, two (6%) (one with a superficially invasive cancer and one with new area of high-grade PAIN). Treatment was well tolerated with most common adverse events being mild to moderate affecting lesional skin: pain/burning/irritation (25 patients) and ulceration (13 patients).ConclusionTopical cidofovir had 51% efficacy in the short-term treatment of high-grade PAIN and VIN with acceptable toxicity in HIV-positive individuals. Randomized control studies with more prolonged treatment courses and longer follow-up to assess the durability of the response are needed