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Analysis of human papillomavirus type 18 load and integration status from low-grade cervical lesion to invasive cervical cancer.

ABSTRACT: The clinical value of viral load and integration testing for human papillomavirus (HPV) remains unclear. Data on HPV type 18 (HPV18) is limited. We examined the HPV18 viral load and integration status of 78 women with normal cervix or neoplasia. While the crude viral load appeared to increase with lesion severity, the association was not significant after normalization with sample cellularity. Unlike reports for HPV16, the amino-terminal 1 region of HPV18 E2 was most frequently (71.0%) disrupted, representing the best marker for integration. A substantial proportion (57.1%) of invasive cancers harbored only the episomal genome, thus jeopardizing the clinical value of integration testing. A large proportion (41.7%) of normal/low-grade lesions showed viral integration, suggesting that integration of HPV18 starts early and is unlikely to be a sole determinant for progression. Interpretation of viral load should take into account the form of HPV infection as single infections had significantly higher viral loads than coinfections (P = 0.046). More data generated from routinely collected samples are warranted to verify the clinical value of viral load and integration testing. Viral load quantitation for HPV18 is premature for clinical use at this stage.

SUBMITTER: Cheung JL

PROVIDER: S-EPMC2643667 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Analysis of human papillomavirus type 18 load and integration status from low-grade cervical lesion to invasive cervical cancer.

Cheung Jo L K JL Cheung Tak-Hong TH Ng Candy W Y CW Yu Mei Y MY Wong Martin C S MC Siu Shing-Shun N SS Yim So-Fan SF Chan Paul K S PK

Journal of clinical microbiology 20081126 2

The clinical value of viral load and integration testing for human papillomavirus (HPV) remains unclear. Data on HPV type 18 (HPV18) is limited. We examined the HPV18 viral load and integration status of 78 women with normal cervix or neoplasia. While the crude viral load appeared to increase with lesion severity, the association was not significant after normalization with sample cellularity. Unlike reports for HPV16, the amino-terminal 1 region of HPV18 E2 was most frequently (71.0%) disrupted ...[more]

PMID: 19036939

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Project description:BackgroundPersistent infection with oncogenic Human Papillomavirus (HPV) is associated with the development of cervical cancer with each genotype differing in their relative contribution to the prevalence of cervical disease. HPV DNA testing offers improved sensitivity over cytology testing alone but is accompanied by a generally low specificity. Potential molecular markers of cervical disease include type-specific viral load (VL), integration of HPV DNA into the host genome and methylation of the HPV genome. The aim of this study was to evaluate the relationship between HPV type-specific viral load, integration and methylation status and cervical disease stage in samples harboring HPV16, HPV18, HPV31 or HPV45.MethodsSamples singly infected with HPV16 (n=226), HPV18 (n=32), HPV31 (n=75) or HPV45 (n=29) were selected from a cohort of 4,719 women attending cervical screening in England. Viral load and integration status were determined by real-time PCR while 3'L1-URR methylation status was determined by pyrosequencing or sequencing of multiple clones derived from each sample.ResultsViral load could differentiate between normal and abnormal cytology with a sensitivity of 75% and a specificity of 80% (odds ratio [OR] 12.4, 95% CI 6.2-26.1; p<0.001) with some variation between genotypes. Viral integration was poorly associated with cervical disease. Few samples had fully integrated genomes and these could be found throughout the course of disease. Overall, integration status could distinguish between normal and abnormal cytology with a sensitivity of 72% and a specificity of 50% (OR 2.6, 95% CI 1.0-6.8; p=0.054). Methylation levels were able to differentiate normal and low grade cytology from high grade cytology with a sensitivity of 64% and a specificity of 82% (OR 8.2, 95% CI 3.8-18.0; p<0.001). However, methylation varied widely between genotypes with HPV18 and HPV45 exhibiting a broader degree and higher magnitude of methylated CpG sites than HPV16 and HPV31.ConclusionsThis study lends support for HPV viral load and CpG methylation status, but not integration status, to be considered as potential biomarkers of cervical disease.

Dataset Information

Analysis of human papillomavirus type 18 load and integration status from low-grade cervical lesion to invasive cervical cancer.

Publications

Analysis of human papillomavirus type 18 load and integration status from low-grade cervical lesion to invasive cervical cancer.

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