Human papillomavirus mRNA testing for the detection of anal high-grade squamous intraepithelial lesions in men who have sex with men infected with HIV.

Currently, screening for anal high-grade squamous intraepithelial lesions (anal HSIL) relies on anal cytology and high-resolution anoscopy. Since this approach has limited sensitivity and specificity for detecting anal HSIL, there is increasing interest in the role of biomarkers for predicting anal HSIL. The aim of this study is to evaluate the diagnostic accuracy of HPV E6/E7-mRNA expression for the detection of anal HSIL in MSM infected with HIV, in comparison to DNA-HR-HPV and anal cytology. This cross-sectional screening study included 101 MSM followed at the HIV-unit of La Paz University Hospital. Intra-anal swabs from patients participating in a screening program including cytology, high-resolution anoscopy and histology were analyzed. HR-HPV-DNA detection was performed by means of the CLART® HPV2 assay (GENOMICA S.A.U., Madrid, Spain). E6/E7-mRNA detection of HR-HPV-types 16, 18, 31, 33, and 45 was performed using the NucliSENS-EasyQ assay (BioMérieux, Marcy ĺEtoile, France). HR-HPV DNA and HPVE6/E7 mRNA were detected in 82% and 57% of the anal smears respectively. Anal cytology screening was abnormal in 70.3%. For the detection of HSIL sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 71.7%, 55.6%, 57.9%, and 69.8% for E6/E7-mRNA testing, respectively, compared to 100%, 31.5%, 55.4%, and 100% for HR-HPV-DNA testing and to 83%, 40.7%, 54.9%, 73.3% of cytology testing. In comparison with the other tests, HPVE6/E7 mRNA testing yielded a lower clinical sensitivity but a higher clinical specificity and PPV for the detection of anal HSIL in MSM infected with HIV.

Sendagorta E ，Romero MP ，Bernardino JI ，Beato MJ ，Alvarez-Gallego M ，Herranz P ... -  《-》

Human papillomavirus oncogene mRNA testing for the detection of anal dysplasia in HIV-positive men who have sex with men.

Anal human papillomavirus (HPV) infection and anal dysplasia are frequent in HIV-positive men who have sex with men (HIV+MSM), and progression of low-grade (LSIL) to high-grade squamous intraepithelial lesions (HSIL) or anal cancer (AC) occurs faster than in HIV-negative individuals. High-risk (HR)-HPV-E6/E7 oncogene mRNA testing has a higher specificity and a higher positive predictive value (PPV) than HR-HPV-DNA testing for detecting high-grade cervical lesions. To evaluate the diagnostic accuracy of the NucliSENS-EasyQ HPV1.1 E6/E7-mRNA-assay for the detection of anal dysplasia in HIV+MSM. 289 intraanal swabs from HIV+MSM participating in a screening program that included anal cytology, high-resolution anoscopy and histology were analyzed. HR-HPV-DNA detection was performed by PCR and hybridization using a bead-based multiplex genotyping assay. E6/E7-mRNA detection of HR-HPV-types 16, 18, 31, 33 and 45 was performed using the NucliSENS-EasyQ assay. 269 swabs had valid results in both test formats (111 normal, 10 ASCUS, 105 LSIL, 42 HSIL, 1 AC). For the detection of LSIL+(LSIL+HSIL+cancer) sensitivity, specificity, negative predictive value (NPV) and PPV were 80.4%, 26.4%, 52.5%, and 57.2% for HR-HPV-DNA testing, respectively, compared to 75.7%, 57.9%, 66.0% and 68.7% for E6/E7-mRNA testing. The respective values for the detection of HSIL/cancer were 95.3%, 26.1%, 96.7%, 19.7% for HR-HPV-DNA and 95.3%, 46.0%, 98.1%, 25.2% for E6/E7-mRNA detection. Compared to HR-HPV-DNA detection, E6/E7-mRNA testing has an increased specificity (approximately two-fold), similar sensitivity and higher NPV and PPV for the detection of low- and high-grade anal dysplasia in HIV+MSM.

Silling S ，Kreuter A ，Hellmich M ，Swoboda J ，Pfister H ，Wieland U ... -  《-》

Comparison of the performance of the NucliSENS EasyQ HPV E6/E7 mRNA assay and HPV DNA chip for testing squamous cell lesions of the uterine cervix.

This study aims to evaluate the clinical performance of the NucliSENS EasyQ assay and compare it with HPV DNA genotyping for the detection of high-grade squamous intraepithelial lesions (HSIL) and cancer in a Korean population. In 188 total thin prep samples, the remaining fluid after cytology slide preparation was tested with Goodgene HPV DNA chips and the NucliSENS EasyQ HPV E6/E7 messenger RNA (mRNA) assay. The sensitivity and specificity of each test were calculated with HSIL and squamous cell carcinoma (SCC) as the disease endpoint. Out of the 188 samples, 139 (74%) were positive for DNA of 14 HPV types, while 57 (30%) cases were positive for E6/E7 mRNA. The DNA test was positive in cytology cases of SCC, HSIL, and atypical squamous cell. The mRNA test yielded results of 75%, 74%, 60%, 56%, and 29% positivity in abnormal cytology cases of SCC, HSIL, atypical squamous cells - cannot exclude HSIL, atypical squamous cells of undetermined significance, and low-grade squamous intraepithelial lesion, respectively. In normal cytology cases, the positivity rates were 9% and 53% for the mRNA and DNA tests, respectively. For detection of HSIL and SCC, the sensitivity of the mRNA test was 74.36% and that of the DNA test was 100%, while the specificities of the tests were 85% and 40.83%, respectively. These findings suggest that the HPV E6/E7 mRNA assay can overcome the shortcoming of low specificity of DNA assays for clinical detection of high-grade cervical lesions and malignancies.

Munkhdelger J ，Choi Y ，Lee D ，Kim S ，Kim G ，Park S ，Choi E ，Jin H ，Jeon BY ，Lee H ，Park KH ... -  《-》

The role of polymerase chain reaction of high-risk human papilloma virus in the screening of high-grade squamous intraepithelial lesions in the anal mucosa of human immunodeficiency virus-positive males having sex with males.

Hidalgo-Tenorio C ，Rivero-Rodriguez M ，Gil-Anguita C ，Esquivias J ，López-Castro R ，Ramírez-Taboada J ，de Hierro ML ，López-Ruiz MA ，Martínez RJ ，Llaño JP ... -  《PLoS One》

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.

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. 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. 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+. 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.

Clarke MA ，Cheung LC ，Lorey T ，Hare B ，Landy R ，Tokugawa D ，Gage JC ，Darragh TM ，Castle PE ，Wentzensen N ... -  《-》