Automated Evaluation of p16/Ki-67 Dual-Stain Cytology as a Biomarker for Detection of Anal Precancer in Men Who Have Sex With Men and Are Living With Human Immunodeficiency Virus.

BACKGROUND: Human papillomavirus-related biomarkers such as p16/Ki-67 "dual-stain" (DS) cytology have shown promising clinical performance for anal cancer screening. Here, we assessed the performance of automated evaluation of DS cytology (automated DS) to detect anal precancer in men who have sex with men (MSM) and are living with human immunodeficiency virus (HIV). METHODS: We conducted a cross-sectional analysis of 320 MSM with HIV undergoing anal cancer screening and high-resolution anoscopy (HRA) in 2009-2010. We evaluated the performance of automated DS based on a deep-learning classifier compared to manual evaluation of DS cytology (manual DS) to detect anal intraepithelial neoplasia grade 2 or 3 (AIN2+) and grade 3 (AIN3). We evaluated different DS-positive cell thresholds quantified by the automated approach and modeled performance compared with other screening strategies in a hypothetical population of MSM with HIV. RESULTS: Compared with manual DS, automated DS had significantly higher specificity (50.9% vs 42.2%; P < .001) and similar sensitivity (93.2% vs 92.1%) for detection of AIN2+. Human papillomavirus testing with automated DS triage was significantly more specific than automated DS alone (56.5% vs 50.9%; P < .001), with the same sensitivity (93.2%). In a modeled analysis assuming a 20% AIN2+ prevalence, automated DS detected more precancers than manual DS and anal cytology (186, 184, and 162, respectively) and had the lowest HRA referral rate per AIN2+ case detected (3.1, 3.5, and 3.3, respectively). CONCLUSIONS: Compared with manual DS, automated DS detects the same number of precancers, with a lower HRA referral rate.

5-Year Prospective Evaluation of Cytology, Human Papillomavirus Testing, and Biomarkers for Detection of Anal Precancer in Human Immunodeficiency Virus-Positive Men Who Have Sex With Men.

BACKGROUND: Human papillomavirus (HPV)-related biomarkers have shown good cross-sectional performance for anal precancer detection in human immunodeficiency virus-positive (HIV+) men who have sex with men (MSM). However, the long-term performance and risk stratification of these biomarkers are unknown. Here, we prospectively evaluated high-risk (HR) HPV DNA, HPV16/18 genotyping, HPV E6/E7 messenger RNA (mRNA), and p16/Ki-67 dual stain in a population of HIV+ MSM. METHODS: We enrolled 363 HIV+ MSM between 2009-2010, with passive follow-up through 2015. All had anal cytology and a high-resolution anoscopy at baseline. For each biomarker, we calculated the baseline sensitivity and specificity for a combined endpoint of high-grade squamous intraepithelial lesion (HSIL) and anal intraepithelial neoplasia grade 2 or more severe diagnoses (HSIL/AIN2+), and we estimated the 2- and 5-year cumulative risks of HSIL/AIN2+ using logistic and Cox regression models. RESULTS: There were 129 men diagnosed with HSIL/AIN2+ during the study. HR-HPV testing had the highest positivity and sensitivity of all assays, but the lowest specificity. HPV16/18 and HPV E6/E7 mRNA had high specificity, but lower sensitivity. The 2- and 5-year risks of HSIL/AIN2+ were highest for those testing HPV16/18- or HPV E6/E7 mRNA-positive, followed by those testing dual stain-positive. Those testing HR-HPV- or dual stain-negative had the lowest 2- and 5-year risks of HSIL/AIN2+. CONCLUSIONS: HPV-related biomarkers provide long-term risk stratification for anal precancers. HR-HPV- and dual stain-negativity indicate a low risk of HSIL/AIN2+ for at least 2 years, compared with negative anal cytology; however, the high positivity of HR-HPV in HIV+ MSM may limit its utility for surveillance and management in this population.

STD screening of HIV-infected MSM in HIV clinics.

BACKGROUND: National guidelines for the care of human immunodeficiency virus (HIV)-infected persons recommend asymptomatic routine screening for sexually transmitted diseases (STDs). Our objective was to determine whether providers who care for HIV-infected men who have sex with men (MSM) followed these guidelines. METHODS: We abstracted medical records to evaluate STD screening at 8 large HIV clinics in 6 US cities. We estimated the number of men who had at least one test for syphilis, chlamydia (urethral and/or rectal), or gonorrhea (urethral, rectal, and/or pharyngeal) in 2004, 2005, and 2006. Urethral testing included nucleic acid amplification tests of both urethral swabs and urine. We also calculated the positivity of syphilis, chlamydia, and gonorrhea among screened men. RESULTS: Medical records were abstracted for 1334 HIV-infected MSM who made 14,659 visits from 2004-2006. The annual screening rate for syphilis ranged from 66.0% to 75.8% during 2004-2006. Rectal chlamydia and rectal and pharyngeal gonorrhea annual screening rates ranged from 2.3% to 8.5% despite moderate to high positivity among specimens from asymptomatic patients (3.0%-9.8%) during this period. Annual urethral chlamydia and gonorrhea screening rates were higher than rates for nonurethral sites, but were suboptimal, and ranged from 13.8% to 18.3%. CONCLUSIONS: Most asymptomatic HIV-infected MSM were screened for syphilis, indicating good provider adherence to this screening guideline. Low screening rates for gonorrhea and chlamydia, especially at rectal and pharyngeal sites, suggest that substantial barriers exist for complying with these guidelines. The moderate to high prevalence of asymptomatic chlamydial and gonococcal infections underscores the importance of screening. A range of clinical quality improvement interventions are needed to increase screening, including increasing the awareness of nucleic acid amplification tests for nonurethral screening.

Low-power transverse ultrasonic treatment of portal vein thrombosis in an animal model.

PURPOSE: The authors have recently developed a small-diameter, thin, flexible ultrasonic catheter device that permits the removal of thrombus by low-power transverse ultrasonic cavitation energy. In this study, the authors sought to determine whether this device could be used to eliminate portal vein thrombosis in an animal model. MATERIALS AND METHODS: In five anesthetized pigs, a total of six occlusions of the left portal vein were achieved with use of autologous clot with (n = 2) or without (n = 4) thrombin injection (250 U) introduced via a 7-F transhepatic catheter/sheath system. Angiographic examination documented complete occlusion of this vessel. The 75-cm-long, 21-gauge ultrasonic catheter (Resolution) was introduced into the clot under angiographic guidance via the transhepatic sheath. Transverse-wave ultrasonic energy was then delivered from the distal 5 cm of the probe at 3.5 W +/- 10% power for up to 6 minutes. Repeat angiographic studies were performed to document patency. After the procedure, gross and histopathologic examinations were performed. RESULTS: Restoration of patency of the main left portal vein was documented in all cases at angiography, with no evidence of residual clot fragments in the major branches. However, side branches demonstrated small thrombotic plugs on pathologic examination. No complications such as perforation of the vessel adjacent to the active ultrasonic tip were encountered. Virtually all thrombolysis was documented to occur within the first minute of energy application. At gross pathologic examination, there was no evidence of damage to the portal vein, and histopathologic examination demonstrated minimal intimal disruption without damage to the media. CONCLUSIONS: This preliminary animal study suggests the feasibility of a percutaneous transhepatic approach to the treatment of portal vein thrombosis with use of low-power ultrasonic cavitation energy. With further study, this method may have potential for the treatment of thrombotic disease, thereby offering novel therapy to patients with thrombotic vascular occlusions.