title: Evaluation of human papillomavirus type replacement postvaccination must account for diagnostic artifacts: masking of HPV52 by HPV16 in anogenital specimens.
abstract: It has been hypothesized that, following a reduction in human papillomavirus (HPV) vaccine-targeted genotypes, an increase in prevalence of other HPV types may occur due to reduced competition during natural infection. Any apparent postvaccination increase must be distinguished from diagnostic artifacts consequent to consensus PCR assays failing to detect HPV types present in low copy numbers in coinfected specimens (under the assumption that with a drop in vaccine-preventable types there may be increased detection of previously "masked" types). We reanalyzed anogenital specimens to evaluate unmasking of HPV52 that may be caused by elimination of HPV16. Using highly sensitive type-specific real-time HPV52 PCR, we retested 1,200 anogenital specimens (all HPV52 negative according to consensus PCR assays) from six epidemiologic studies (200 specimens/study; 100 HPV16(+)/study). Multivariate logistic regression, with adjustment for age and number of sexual partners, was used to evaluate the association between HPV16 positivity and detection of HPV52. In our pooled analysis (n = 1,196), the presence of HPV16 was positively associated with HPV52 detection [adjusted OR, 1.47; 95% confidence interval (CI), 0.76-2.82]. In our separate (study specific) analyses, a statistically significant association was observed in one study that included HIV-infected males (HIPVIRG study; adjusted OR, 3.82; 95% CI, 1.19-12.26). We observed a positive association between HPV16 viral load (tertiles) and detection of HPV52 (P for trend = 0.003). These results indicate that diagnostic artifacts, resulting from unmasking of HPV52, may occur in some settings in the evaluation of HPV type replacement. Additional studies exploring the extent and severity of unmasking are needed.
authors.affiliation: Department of Oncology (Division of Cancer Epidemiology), McGill University, Montreal, Québec, Canada. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Québec, Canada. joseph.tota@mail.mcgill.ca.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Tota
authors.affiliation: Department of Oncology (Division of Cancer Epidemiology), McGill University, Montreal, Québec, Canada.
authors.forename: Agnihotram V
authors.initials: AV
authors.lastname: Ramanakumar
authors.affiliation: Department of Radiology and Oncology, School of Medicine, Universidade de São Paulo, São Paulo, Brazil. Santa Casa de São Paulo, School of Medicine, São Paulo, Brazil.
authors.forename: Luisa L
authors.initials: LL
authors.lastname: Villa
authors.affiliation: Department of Community Health and Epidemiology, Queens University, Kingston, Ontario, Canada.
authors.forename: Harriet
authors.initials: H
authors.lastname: Richardson
authors.affiliation: Department of Oncology (Division of Cancer Epidemiology), McGill University, Montreal, Québec, Canada. Ontario HIV Treatment Network, Toronto, Ontario, Canada.
authors.forename: Ann N
authors.initials: AN
authors.lastname: Burchell
authors.affiliation: Département de médecine sociale et préventive, Université de Montréal, Montreal, Québec, Canada. Université de Montréal Hospital Research Centre, Montreal, Québec, Canada.
authors.forename: Anita
authors.initials: A
authors.lastname: Koushik
authors.affiliation: Université de Montréal Hospital Research Centre, Montreal, Québec, Canada. Université de Montréal, Département d'obstétrique-gynécologie et Médecine Sociale et Préventive, Montreal, Québec, Canada.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Mayrand
authors.affiliation: Université de Montréal Hospital Research Centre, Montreal, Québec, Canada. Université de Montréal, Département de Microbiologie et Infectiologie, Montreal, Québec, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Coutlée
authors.affiliation: Department of Oncology (Division of Cancer Epidemiology), McGill University, Montreal, Québec, Canada. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Québec, Canada.
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Franco
mesh_terms: D001004:Anus Diseases / Q000175:diagnosis*; D015331:Cohort Studies; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D008297:Male; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000175:diagnosis*; D053918:Papillomavirus Vaccines / Q000235:genetics*
chemical_list: D053918:Papillomavirus Vaccines