Abstract
There are more than 40 human papillomaviruses (HPVs) belonging to the alpha genus that cause sexually transmitted infections; these infections are among the most frequent and can lead to condylomas and anogenital intra-epithelial neoplasia. At least 18 of these viruses are causative agents of anogenital carcinomas. We evaluated the performance of a resequencing microarray for the detection and genotyping of alpha HPV of clinical significance using cloned HPV DNA. To reduce the number of HPV genotypes tiled on microarray, we used reconstructed ancestral sequences (RASs) as they are more closely related to the various genotypes than the current genotypes are among themselves. The performance of this approach was tested by genotyping with a set of 40 cervical smears already genotyped using the commercial PapilloCheck kit. The results of the two tests were concordant for 70% (28/40) of the samples and compatible for 30% (12/40). Our findings indicate that RASs were able to detect and identify one or several HPV in clinical samples. Associating RASs with homonym sequences improved the genotyping of HPV present in cases of multiple infection. In conclusion, we demonstrate the diagnostic potential of resequencing technology for genotyping of HPV, and illustrate its value both for epidemiological studies and for monitoring the distribution of HPV in the post-vaccination era.
Highlights
More than 170 human papillomavirus (HPVs) have been characterized and they are classified into the alpha, beta, gamma, mu, and nu genera [1]
Multiple broad-spectrum PCR methods have been developed for the detection of the alpha-human papillomaviruses (HPVs) genus and most are based on HPV sequences in the L1 open reading frame
We show that resequencing microarray (RMA) technology was feasible and effective for genotyping human papillomaviruses, and is a potentially valuable tool for epidemiology
Summary
More than 170 human papillomavirus (HPVs) have been characterized and they are classified into the alpha, beta, gamma, mu, and nu genera [1]. Some alpha papillomaviruses presenting a mucous tropism cause some of the most frequent sexually transmitted infections: around 300 million women worldwide carry a HPV infection of the uterine cervix. Low-risk mucosal HPVs (LR HPVs) are responsible for condylomas found in 1–2% of the sexually active population. High-risk HPVs (HR HPVs) are causative agents of more than 80% of high-grade cervical intra-epithelial neoplasia [2]. Persistent lesions associated with HR HPVs may evolve towards invasive cervical carcinomas. HPV DNA sequences are detected in the vast majority of adenocarcinomas, adenosquamous carcinomas and squamous cell carcinomas of the cervix, all of which are preceded by premalignant lesions [3]. HR HPVs contributes to the pathogenesis of other anogenital and aero-digestive tract cancers [4]
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