Martyn Plummer, Salvatore Vaccarella and Silvia Franceschi
In this issue of the Journal of Infectious Diseases, Chaturvedi et al [ 1] report on a large epidemiological study of human papillomavirus (HPV) infection focusing on a topic of increasing interest in this field. HPV is recognized as a necessary cause of cervical cancer, but there are multiple oncogenic HPV types that may be found together in the same woman. What do such multiple infections mean, and how can they be analyzed in the context of epidemiological studies?
In the earliest studies of HPV, multiple infections were seldom detected [ 2]. This is likely to be due to the characteristics of the earliest diagnostic tests. Some, such as Hybrid Capture 2 (HC2) (Qiagen, Gaithersburg, MD), do not distinguish individual HPV types, and the first polymerase chain reaction (PCR)–based assays included relatively few types other than HPV-16 and HPV-18. In the past decade, however, PCR-assays have become available that can detect broader ranges of oncogenic and nononcogenic HPV types ( n > 40) and, most notably, have much higher analytical sensitivity (ie, ability to identify correctly HPV-positive women) [ 3, 4]. In a recent cross-wise comparison of 4 widely used PCR assays among women who had previously tested positive by HC2, the rate of detection of HPV infection ranged from 62.6% to 91.4%, and the proportion of multiple infections among all HPV-positive tests ranged from 24.8% to 52.6% [ 5]. This shows that there can be substantial disagreement even between high-quality PCR assays. The concordance between tests greatly increased, however, with increasing viral load and when the presence of cervical intra-epithelial neoplasia 2 or worse (CIN2+) rather than HPV infection was set as an end point (clinical sensitivity) [ 5], [ 6]. …
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