Detection of Human Papillomavirus Type 16 DNA in Consecutive Genital Samples Does Not Always Represent Persistent Infection  as Determined by Molecular Variant Analysis

Mayrand, Marie‐Hélène; Coutlée, François; Hankins, Catherine; Lapointe, Normand; Forest, Pierre; Ladurantaye, Manon de; Roger, Michel

doi:10.1128/jcm.38.9.3388-3393.2000

Cited by 44 publications

(8 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multiple infections by HPV-16 molecular variants were detected in approximately 10% of the cases. Similar frequencies of coinfection by different variants in cancer samples have been described by others [Mayrand et al, 2000;Pérez-Gallego et al, 2001]. However in cervical smears from asymptomatic women this event was reported to be rare [Sichero et al, 2007a].…”

Section: Discussionsupporting

confidence: 84%

Human papillomavirus type 16 variants in cervical cancer from an admixtured population in Brazil

Junes-Gill

Sichero²,

Maciag³

et al. 2008

Journal of Medical Virology

View full text Add to dashboard Cite

Several studies indicate that molecular variants of HPV-16 have different geographic distribution and risk associated with persistent infection and development of high-grade cervical lesions. In the present study, the frequency of HPV-16 variants was determined in 81 biopsies from women with cervical intraepithelial neoplasia grade III or invasive cervical cancer from the city of Belem, Northern Brazil. Host DNAs were also genotyped in order to analyze the ethnicity-related distribution of these variants. Nine different HPV-16 LCR variants belonging to four phylogenetic branches were identified. Among these, two new isolates were characterized. The most prevalent HPV-16 variant detected was the Asian-American B-2, followed by the European B-12 and the European prototype. Infections by multiple variants were observed in both invasive cervical cancer and cervical intraepithelial neoplasia grade III cases. The analysis of a specific polymorphism within the E6 viral gene was performed in a subset of 76 isolates. The E6-350G polymorphism was significantly more frequent in Asian-American variants. The HPV-16 variability detected followed the same pattern of the genetic ancestry observed in Northern Brazil, with European, Amerindian and African roots. Although African ancestry was higher among women infected by the prototype, no correlation between ethnical origin and HPV-16 variants was found. These results corroborate previous data showing a high frequency of Asian-American variants in cervical neoplasia among women with multiethnic origin.

show abstract

Section: Discussionsupporting

confidence: 84%

Human papillomavirus type 16 variants in cervical cancer from an admixtured population in Brazil

Junes-Gill

Sichero²,

Maciag³

et al. 2008

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…There is evidence by molecular variant analysis that detection of HPV 16 DNA in consecutive samples obtained at 6-month intervals does not always represent infection that persisted in that period [13]. This supports the second possibility above.…”

Section: Transient Infection Between V M and V M+1 That Clears Aftersupporting

confidence: 62%

Evaluation of log‐rank tests for infrequent observations from a multi‐state process, with application to HPV vaccine efficacy

Kang

Lagakos

2004

Statistics in Medicine

View full text Add to dashboard Cite

Genital infection by human papillomavirus (HPV) is a common sexually transmitted disease, with over 25 per cent prevalence among young women in the US. Infections are usually without symptoms and transient (or reversible), but a small proportion of infections persist and are believed to be responsible for nearly all cervical cancers and precursor lesions such as cervical intraepithelial neoplasia (CIN). Therefore, successful vaccines against persistent HPV infections could have a great impact in preventing cervical cancers. In trials being planned, ongoing, and recently completed, a log-rank or a similar test may be employed to assess a vaccine effect in comparison to placebo, with an infection 'event' defined to capture persistent but not transient infections. However, it is not clear how best to define such an event, because (1) diagnostic tests cannot distinguish a persistent from a transient infection, (2) participants are only examined periodically, and (3) there can be misclassification errors in the detection of infections. This paper evaluates several definitions of persistent infection that are based on periodically observed infection statuses by postulating a multi-state model for persistent and transient infections. The type I error and the power of tests on vaccine efficacy based on these operational definitions are then examined under various scenarios of how a vaccine might affect the infection-disease process. We find that none of the candidates performs satisfactorily, thus raising concerns that clinical trials based only on infection endpoints will not be reliable.

show abstract

“…One of the first studies to explore genomic diversity of HPV types was actually initiated to distinguish between natural HPV infections and PCR contaminations 11. Subsequent studies utilized the genomic variation seen in HPV‐16 to differentiate persistent infections from de novo infection with another HPV‐16 variant 31, 32. Comparison of HPV‐16 infections in couples confirmed the efficient sexual exchange of variants, but also identified cases where the most conspicuous lesions of sexual partners contained different HPV‐16 genomes, inferring either inefficient transmission of virus or, more likely, inefficient pathogenesis after transmission of virus from one partner to the other 33.…”

Section: Genomic Variation As a Tool In Etiological Researchmentioning

confidence: 99%

Genome variation of human papillomavirus types: Phylogenetic and medical implications

Bernard

Calleja-Macías

Dunn

2005

Intl Journal of Cancer

265

210

View full text Add to dashboard Cite

Human papillomaviruses (HPVs) are described as ''types'' based on their genome sequences and identified by a number. For example, HPV-6 is associated with genital warts, and HPV-16 with anogenital cancers. The genomes of many HPV types have been reisolated, sequenced and compared to reference ''prototypes'' countless times by laboratories throughout the world. It was found that each HPV type occurs in the form of ''variants'', identified by about 2% nucleotide differences in most genes and 5% in less conserved regions. Less than 100 variants of any HPV type have been detected, a scenario that is very different from the quasi-species formed by many RNA viruses. The variants of each HPV type form phylogenetic trees, and variants from specific branches are often unique to specific ethnic groups. Immigrant populations contain, depending on their respective ethnic origins, mixtures of variants. The absence of HPV genomes intermediate to specific types show that all HPV types existed already when humans became a species. Consequently, humans had always suffered from lesions like anogenital cancer, genital warts and common warts. A growing number of epidemiological, etiological and molecular data suggest that variants of the same HPV type are biologically distinct and may confer differential pathogenic risks. Since the distribution of some variants of HPV-16 and 18 correlates with the distribution of human populations that have an increased risk to develop anogenital cancer, the study of HPV type variation may point to one of the reasons for the higher incidence rates of these lesions in specific cohorts. ' 2005 Wiley-Liss, Inc.Key words: papillomavirus; evolution; epidemiology; etiology Papillomavirus (PV) genomes comprise 8 kb of doublestranded, circular DNA with 8 protein-coding genes (L1 and L2 that encode capsid proteins and E1, E2, E4, E5, E6 and E7 that encode proteins involved in replication, transcription and transformation) and a noncoding, regulatory long control region (LCR). The genomes of PVs change by point mutations, deletions and insertions just like those of their hosts. Mutations occur fortuitously but can become established in a population if there is some mechanism that positively selects for the mutant, or, if they are functionally neutral, by selective expansion of the host population infected with the mutant (genetic drift). DNA genomes change much slower than RNA genomes, because of the proofreading abilities of DNA polymerases. As an example, the most remotely related PV genomes have a nucleotide diversity of about 50%, established during coevolution with their mammalian hosts over millions of years. By contrast, the RNA-based HIV-1 genomes within a single AIDS patient can diverge to a similar extent during a 10-year-infection. PV genomes are further stabilized by the apparent absence of inter-and intra-type recombination. Diversification of PV genomes is also limited by the slow replication of the virus in synchrony with division of the host epithelial cells. Since the replication rate of ep...

show abstract

Detection of Human Papillomavirus Type 16 DNA in Consecutive Genital Samples Does Not Always Represent Persistent Infection as Determined by Molecular Variant Analysis

Cited by 44 publications

References 37 publications

Human papillomavirus type 16 variants in cervical cancer from an admixtured population in Brazil

Human papillomavirus type 16 variants in cervical cancer from an admixtured population in Brazil

Evaluation of log‐rank tests for infrequent observations from a multi‐state process, with application to HPV vaccine efficacy

Genome variation of human papillomavirus types: Phylogenetic and medical implications

Contact Info

Product

Resources

About