TY - JOUR T1 - Efficacy and safety of prophylactic HPV vaccines. A Cochrane review of randomized trials. JF - Expert Rev Vaccines Y1 - 2018 A1 - M. Arbyn A1 - Lan Xu KW - Cervical cancer; HPV vaccines; meta-analysis; randomized clinical trials; safety; systematic review. AB -

Introduction: Recently, the evidence on efficacy and safety of prophylactic HPV vaccines derived from randomized trials was published in the Cochrane database of Systematic reviews. A summary of this Cochrane review is presented below.

Areas covered: Only trials involving mono-, bi-, and quadrivalent HPV vaccines were included. Trials evaluating the nonavalent vaccine were excluded since women in the control group received the quadrivalent vaccine. Main efficacy outcomes were: histologically confirmed cervical precancer lesions distinguishing those associated with vaccine HPV types and any cervical precancer. Exposure groups were: women aged: 15-26 or 24-45 years being initially negative for high-risk HPV (hrHPV) or negative for the vaccine types and women unselected by HPV status.

Expert commentary: All evaluated vaccines offered excellent protection against cervical intraepithelial neoplasia of grade 2 or 3 (CIN2 or CIN3) and adenocarcinoma in situ associated with HPV16/18 infection in young women who were not initially infected with hrHPV or HPV16/18. Vaccine efficacy was lower when all women regardless of HPV DNA status at enrollment were included. In young women, HPV vaccination protected also against any cervical precancer but the magnitude of protection was lower than against HPV16/18 associated cervical precancer. Vaccine efficacy was lower in mid-adult (aged 24-45 years) women. No protection against cervical precancer was found in mid-adult women unselected by HPV DNA status at enrollment. Trials were not empowered to address protection against cervical cancer. Occurrence of severe adverse events or adverse pregnancy outcomes was not significantly higher in recipients of HPV vaccines than in women included in the control arms.

VL - 17 CP - 12 M3 - 10.1080/14760584.2018.1548282 ER - TY - JOUR T1 - Evaluation of the clinical performance of the HPV-Risk assay using the VALGENT-3 panel. JF - J Clin Microbiol Y1 - 2017 A1 - Polman, N J A1 - Oštrbenk, A A1 - Lan Xu A1 - Snijders, P J F A1 - Meijer, C J L M A1 - Poljak, M A1 - Heideman, D A M A1 - M. Arbyn AB -

Human papillomavirus (HPV) testing is being increasingly incorporated into cervical cancer screening. VALGENT (VALidation of HPV GENotyping Tests) is a framework designed to evaluate the clinical performance of various HPV tests relative to the validated and accepted comparator test in a formalized and uniform manner. The aim of this study was to evaluate the clinical performance of the HPV-Risk assay within the VALGENT-3 panel, and to compare its performance to the clinically validated Hybrid Capture 2 assay (HC2). The VALGENT-3 panel comprises 1,300 consecutive samples from women participating in the routine cervical cancer screening, enriched with 300 samples from women with abnormal cytology. DNA was extracted from original ThinPrep aliquots and HPV testing was performed using the HPV-Risk assay, blinded to the clinical data. HPV prevalence was analysed and clinical performance for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and CIN2 or worse (CIN2+) was assessed relative to the performance of the HC2. The sensitivity of the HPV-Risk assay for detection of CIN3+ was similar to that of the HC2 (relative sensitivity: 1.00; 95%CI: 0.95-1.05; p=1.000) with significantly higher specificity (relative specificity: 1.02; 95%CI: 1.01-1.04; p<0.001). For CIN2+, similar results were obtained with relative sensitivity of 0.98; 95%CI: 0.93-1.02 and relative specificity of 1.02; 95%CI: 1.01-1.03. The performance of the HPV-Risk assay for CIN3+ and CIN2+ was non-inferior compared to the HC2, with all p-values ≤0.006. In conclusion, the HPV-Risk assay demonstrated non-inferiority to the clinically validated HC2 through the VALGENT-3 panel for test validation and comparison.

U1 - http://www.ncbi.nlm.nih.gov/pubmed/29021152?dopt=Abstract M3 - 10.1128/JCM.01282-17 ER - TY - JOUR T1 - Genotyping for Human Papillomavirus Types 16 and 18 in Women With Minor Cervical Lesions: A Systematic Review and Meta-analysis. JF - Ann Intern Med Y1 - 2017 A1 - M. Arbyn A1 - Lan Xu A1 - Verdoodt, Freija A1 - Cuzick, Jack A1 - Szarewski, Anne A1 - Belinson, Jerome L A1 - Wentzensen, Nicolas A1 - Gage, Julia C A1 - Khan, Michelle J KW - Early Detection of Cancer KW - Female KW - Genotype KW - Human papillomavirus 16 KW - Human papillomavirus 18 KW - Humans KW - Papillomavirus Infections KW - Precancerous Conditions KW - Risk Factors KW - Sensitivity and Specificity KW - triage KW - Uterine Cervical Neoplasms AB -

Background: High-risk human papillomavirus (hrHPV) testing to triage women with minor cervical lesions generates many referrals.

Purpose: To evaluate the accuracy of genotyping for HPV types 16 and 18 and its utility as a second triage step after hrHPV testing in women with minor cervical lesions.

Data Sources: Searches of 4 bibliographic databases, without language restrictions, from 1 January 1999 to 1 February 2016.

Study Selection: Studies involving women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL) who were triaged with tests for hrHPV and HPV 16/18 to find cervical intraepithelial neoplasia (grade ≥2 [CIN2+] or grade ≥3 [CIN3+]).

Data Extraction: Independent study selection, extraction of data, and quality assessment by 2 reviewers.

Data Synthesis: Twenty-four moderate- to good-quality studies involving 8587 women with ASC-US and 5284 with LSIL were found. The pooled sensitivity of HPV 16/18 genotyping for CIN3+ was about 70% for women with either ASC-US or LSIL. The pooled specificity (with a threshold of grade <2 CIN) was 83% (95% CI, 80% to 86%) for women with ASC-US and 76% (CI, 74% to 79%) for those with LSIL. The average risk for CIN3+ was 17% and 19% in HPV 16/18-positive women with ASC-US and LSIL, respectively, and was 5% in hrHPV-positive but HPV 16/18-negative women with either ASC-US or LSIL.

Limitation: Methodological and technical heterogeneity among studies; insufficient data to assess accuracy of separate assays.

Conclusion: Testing for HPV 16/18 to triage women with minor abnormal cytology is poorly sensitive but may be useful as a second triage test after hrHPV testing, with direct referral if the woman is positive for HPV 16/18. Whether colposcopy or repeated testing is recommended for hrHPV-positive but HPV 16/18-negative women depends on local decision thresholds that can be derived from pretest-posttest probability plots.

Primary Funding Source: 7th Framework Programme of the European Commission.

VL - 166 CP - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27842420?dopt=Abstract M3 - 10.7326/M15-2735 ER - TY - JOUR T1 - Reply to HPV test results provide useful risk stratification information in women with ASC-H Pap test findings. JF - Cancer Y1 - 2016 A1 - M. Arbyn A1 - Lan Xu A1 - Wentzensen, Nicolas VL - 124 CP - 10 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27336222?dopt=Abstract M3 - 10.1002/cncy.21754 ER - TY - JOUR T1 - Triage of ASC-H: A meta-analysis of the accuracy of high-risk HPV testing and other markers to detect cervical precancer. JF - Cancer Cytopathol Y1 - 2016 A1 - Lan Xu A1 - Verdoodt, Freija A1 - Wentzensen, Nicolas A1 - Bergeron, Christine A1 - M. Arbyn KW - Atypical Squamous Cells of the Cervix KW - Early Detection of Cancer KW - Female KW - Human Papillomavirus DNA Tests KW - Humans KW - Neoplasm Invasiveness KW - Neoplasm Staging KW - Papillomavirus Infections KW - Precancerous Conditions KW - Sensitivity and Specificity KW - Squamous Intraepithelial Lesions of the Cervix KW - triage KW - Uterine Cervical Neoplasms KW - Vaginal Smears AB -

BACKGROUND: Women with a cytological diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) are usually immediately referred for colposcopy. However, triage may reduce the burden of the diagnostic workup and prevent overtreatment.

METHODS: A meta-analysis was conducted to assess the accuracy of high-risk human papillomavirus (hrHPV) testing and testing for other molecular markers for the detection of grade 2 cervical intraepithelial neoplasia or worse (CIN2+) or grade 3 cervical intraepithelial neoplasia or worse (CIN3+) in women with ASC-H. An additional question that was assessed was whether triage would be useful in light of the relatively high pretriage probability of underlying precancer.

RESULTS: The pooled absolute sensitivity and specificity of the Hybrid Capture 2 (HC2) assay for CIN2 + (derived from 19 studies) were 93% (95% confidence interval [CI], 89%-95%) and 45% (95% CI, 41%-50%), respectively. p16(INK4a) staining (only 3 studies) had similar sensitivity (93%; 95% CI, 75%-100%) but superior specificity (specificity ratio, 1.69) to HC2 for CIN2+. Testing for paired box 1 gene methylation (only 1 study) showed a superior specificity of 95% (specificity ratio, 2.08). The average pretest risk was 34% for CIN2 + and 20% for CIN3+. A negative HC2 result decreased this to 8% and 5%, respectively, whereas a positive result upgraded the risk to 47% and 28%, respectively.

CONCLUSIONS: Because of the high probability of precancer with a diagnosis of ASC-H, the utility of triage is limited. The usual recommendation for referring women with ASC-H for colposcopy is not altered by a positive triage test, whatever test is used. A negative hrHPV DNA or p16(INK4a) test may allow repeat testing, but this recommendation will depend on local decision thresholds for referral.

VL - 124 CP - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26618614?dopt=Abstract M3 - 10.1002/cncy.21661 ER - TY - JOUR T1 - Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors (Protocol) JF - Cochrane Database Syst.Rev. Y1 - 2013 A1 - M. Arbyn A1 - Bryant,A. A1 - Lan Xu A1 - Cindy Simoens A1 - L. Markowitz KW - a1 KW - abstract KW - Adenocarcinoma KW - age KW - ALL KW - antibodies KW - AS KW - assessment KW - at KW - Belgian Foundation Against Cancer KW - cancer KW - Categories KW - Cervical KW - cervical cancer KW - CERVICAL-CANCER KW - cervix KW - CIN KW - Clinical KW - cochrane KW - CoHeahr KW - Dna KW - ECCG KW - Evaluating KW - EVALUATION KW - Female KW - Females KW - Follow KW - HPV KW - Human KW - INFECTION KW - IS KW - IT KW - objectives KW - outcome KW - outcomes KW - precursor KW - PREHDICT KW - protocol KW - REVIEW KW - SAFETY KW - serology KW - status KW - systematic review KW - time KW - Type KW - Vaccination KW - vaccine KW - vaccines KW - WOMEN AB - This is the protocol for a review and there is no abstract. The objectives are as follows:To evaluate the immunogenicity, clinical efficacy, and safety of prophylactic HPV vaccines in females. The assessment of clinical efficacy will address protection against HPV infection (for homologous and heterologous HPV types), against re-infection, against cervical cancer and its precursors (high-grade CIN (grade 2 or grade 3), adenocarcinoma in situ) in women previously not exposed to HPV infection (negative at enrolment for both HPV DNA and antibodies against the vaccine HPV types). We will assess clinical effectiveness by evaluating outcomes in all women, irrespective of the HPV DNA or serology status at enrolment. Evaluation by fine age and time since sexual debut categories is also planned. VL - 12 CP - CD009069 U1 - 31608 M3 - http://dx.doi.org/ ER -