Publications by authors named "Palefsky J"

Purpose: The Anal Cancer/High-grade squamous intraepithelial lesions Outcomes Research (ANCHOR) trial demonstrated that treating precancerous anal HSIL reduces the incidence of anal cancer by 57% in people with HIV. It remains unclear how HSIL treatment or monitoring without treatment affects patient-reported health-related quality of life (HRQoL). We evaluated differences in HRQoL for individuals who were randomly assigned to active monitoring (AM) or treatment for anal HSIL.

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The growing demand for healthcare services and the burden of diseases such as cancer in sub-Saharan Africa (SSA) requires locally-led and setting-relevant evidence that should be driven by local investigators. However, there is a huge gap in the health research capacity to generate such evidence in most of SSA, particularly in Rwanda. With a changing focus and the willingness of investigators and funders from high-income countries (HICs) to support investigators and research from SSA, it is important to build strong, successful, and sustained partnerships.

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Post hoc analyses of 9-valent human papillomavirus (9vHPV) vaccine immunogenicity were conducted in five Phase 3 studies that enrolled males. Month 7 antibody geometric mean titers (GMTs) after three 9vHPV vaccine doses were analyzed in 10,024 males/females aged 16-26 years from studies 001 (NCT00543543), 002 (NCT00943722), 003 (NCT01651949), and 020 (NCT02114385). Covariates considered were age, gender, sexual orientation, region of residence, and race.

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We studied cervicovaginal β-/γ-human papillomavirus (HPV) and their relationship to cervical precancer in women with HIV (WWH); having previously reported strong positive associations of β-/γ-HPV with incident head and neck cancer in the general population. Cases (N=124) had cervical intraepithelial neoplasia (CIN)-3 or CIN-2. Controls (N=247) were individually matched 2:1 to cases.

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Introduction: The goal of our research programme is to develop culturally appropriate patient-specific interventions for primary and secondary prevention of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) among people living with HIV (PLWH); PLWH are at a higher risk for OPC than the general population and, as with many cancers, there are disparities in OPC health outcomes by race and ethnicity. Our study incorporates an anti-racist research framework that proposes considering racism as a foundational sociocultural system that causes ill health. We expand the framework to include biases due to gender, sexual orientation, HIV status and membership in other non-dominant groups.

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Article Synopsis
  • Anal cancer is primarily caused by HPV, especially HPV-16, and often develops from anal high-grade squamous intraepithelial lesions (HSILs), with the highest incidence seen in men who have sex with men (MSM) living with HIV, particularly those over 50 years old.
  • A study conducted in San Francisco between 2018 and 2022 found high rates of anal HSIL and oncogenic HPV among older MSM, regardless of HIV status; 47% of MSM living with HIV and 37% of MSM not living with HIV had anal HSIL.
  • The results suggest that there is a significant prevalence of high-risk anal HPV types in this age group, indicating a need for anal cancer screening
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Objectives: Anal cancer risk is elevated in MSM with HIV (MSMWH). Anal high-risk human papillomavirus (hr-HPV) infection is necessary but insufficient to develop high-grade squamous intraepithelial lesion (HSIL), the anal cancer precursor, suggesting additional factors. We sought to determine whether the microbiome of the anal canal is distinct by comparing it with the microbiome of stool.

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Background: Little is known about penile high-risk human papillomavirus (hrHPV) among men who have sex with men (MSM) in low- and middle-income countries. We aimed to determine the incidence, clearance, and persistence of penile hrHPV among Rwandan MSM.

Methods: We enrolled 350 MSM (345 with valid human papillomavirus [HPV] results) aged ≥18 years.

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The high incidence of epithelial malignancies in HIV-1 infected individuals is associated with co-infection with oncogenic viruses, such as high-risk human papillomaviruses (HR HPVs), mostly HPV16. The molecular mechanisms underlying the HIV-1-associated increase in epithelial malignancies are not fully understood. A collaboration between HIV-1 and HR HPVs in the malignant transformation of epithelial cells has long been anticipated.

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The International Anal Neoplasia Society (IANS) developed consensus guidelines to inform anal cancer screening use among various high-risk groups. Anal cancer incidence estimates by age among risk groups provided the basis to identify risk thresholds to recommend screening. Guided by risk thresholds, screening initiation at age 35 years was recommended for men who have sex with men (MSM) and transgender women (TW) with HIV.

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Introduction: The American Joint Committee on Cancer (AJCC) staging system undergoes periodic revisions to maintain contemporary survival outcomes related to stage. Recently, the AJCC has developed a novel, systematic approach incorporating survival data to refine stage groupings. The objective of this study was to demonstrate data-driven optimization of the version 9 AJCC staging system for anal cancer assessed through a defined validation approach.

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Article Synopsis
  • The study examined the incidence of anogenital HPV infections in 295 men who have sex with men (MSM) and 1,576 heterosexual men (HM) aged 16-27 years participating in a global HPV vaccine trial.
  • Results showed that MSM had significantly higher incidence rates of persistent HPV infections at various anatomical sites compared to heterosexual men, particularly at anal sites.
  • The findings suggest that gender-neutral HPV vaccination could reduce infections in males, improve overall public health protection, and lessen the disease burden associated with HPV.
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Background: Detection and treatment of anal histologic high-grade squamous intraepithelial lesions (hHSIL) prevents anal cancer. However, anal hHSIL incidence among women with human immunodeficiency virus (HIV, WHIV) remains unknown. Performance of anal high-risk human papillomavirus ([hr]HPV), anal cytology (anal-cyt), and both for hHSIL detection longitudinally over 2 years also remains undetermined.

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The World Health Organization recommends human papillomavirus (HPV) testing for cervical screening. Extended genotyping can identify the highest-risk HPV-positive women. An inexpensive, rapid, mobile isothermal amplification assay (ScreenFire HPV RS test) was recently redesigned to yield four channels ordered by cancer risk (ie, hierarchical approach): HPV16, HPV18/45, HPV31/33/35/52/58 and HPV39/51/56/59/68.

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An estimated 38 million people live with human immunodeficiency virus (HIV) worldwide and are at excess risk for multiple cancer types. Elevated cancer risks in people living with HIV (PLWH) are driven primarily by increased exposure to carcinogens, most notably oncogenic viruses acquired through shared transmission routes, plus acceleration of viral carcinogenesis by HIV-related immunosuppression. In the era of widespread antiretroviral therapy (ART), life expectancy of PLWH has increased, with cancer now a leading cause of co-morbidity and death.

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Background: Anal intraepithelial neoplasia grade III is a precursor to squamous cell carcinoma of the anus for which rates are nearly 20-fold higher in people with HIV than in the general population in the United States. We describe trends in anal intraepithelial neoplasia grade III diagnosis and risk of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III by HIV status and sex.

Methods: We used data from a population-based linkage between cancer and HIV registries in 11 US states; Puerto Rico; and Washington, DC, during 1996-2019.

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The burden of cervical cancer is disproportionately distributed globally, with the vast majority of cases occurring in low- and middle-income countries. Women with human immunodeficiency virus (HIV) (WWH) are at increased risk of human papillomavirus (HPV) infection and cervical cancer as compared to HIV-negative individuals. HPV vaccination remains a priority in regions with a high burden of cervical cancer and high HIV prevalence.

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Background: Cervical cancer oncogenesis starts with human papillomavirus (HPV) cell entry after binding to host cell surface receptors; however, the mechanism is not fully known. We examined polymorphisms in receptor genes hypothesized to be necessary for HPV cell entry and assessed their associations with clinical progression to precancer.

Methods: African American women (N = 1,728) from the MACS/WIHS Combined Cohort Study were included.

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Treatment of screen-detected anal high-grade squamous intraepithelial lesions has been shown to effectively reduce the incidence of invasive anal cancer in people with HIV. We provide population-based estimates of cumulative incidence of anal cancer by risk group and age at HIV or AIDS diagnosis. The 0- to 10-year cumulative incidence of anal cancer for men who have sex with men and are younger than 30 years of age at HIV diagnosis was 0.

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Introduction: The AmpFire HPV genotyping Assay (Atila Biosystems, Mountain View, CA, USA) is a new test for which there are few data regarding its analytic performance and reliability. Using anal and penile swab specimens from a cohort study of men who have sex with men (MSM) in Rwanda, we compared high-risk HPV (hrHPV) detection by AmpFire done at two laboratories, one at University of California San Francisco (UCSF) and the other Rwanda Military Hospital, and well-validated MY09/11-based assay done at UCSF.

Methods: Anal and penile specimens collected from 338 MSM from March 2016 to September 2016 were tested for high-risk HPV genotypes (hrHPV) by MY09/11, AmpFire UCSF and AmpFire RMH.

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The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including anal cancer, is the standard for cancer staging in the United States. The AJCC staging criteria are dynamic, and periodic updates are conducted to optimize AJCC staging definitions through a panel of experts charged with evaluating new evidence to implement changes. With greater availability of large data sets, the AJCC has since restructured and updated its processes, incorporating prospectively collected data to validate stage group revisions in the version 9 AJCC staging system, including anal cancer.

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