Semi‐quantitative human papillomavirus DNA detection in the management of women with minor cytological abnormality

Mansell, M. E.; Ho, Linda; Terry, George; Singer, Albert; Cuzick, Jack

doi:10.1111/j.1471-0528.1994.tb11952.x

Cited by 23 publications

(14 citation statements)

References 12 publications

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“…Many previous studies have found a positive association between viral load and disease severity, which has led to the idea of using viral load as a biomarker to determine the status of cervical disease or to predict its progression (4,11,13,19,23,24,28,30,31). However, at the same time, contradictory data have also been generated (1,15,26,34).…”

Section: Discussionmentioning

confidence: 94%

Analysis of Human Papillomavirus Type 18 Load and Integration Status from Low-Grade Cervical Lesion to Invasive Cervical Cancer

Cheung¹,

Cheung²,

Ng³

et al. 2009

J Clin Microbiol

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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.There is no doubt that infection with human papillomavirus (HPV) may lead to the establishment of cervical cancer (3, 33). Though infection with HPV is common, not all HPV types will lead to cancer. There are 15 high-risk HPV types that have a higher propensity for the development of cervical cancer, with HPV type 16 (HPV16) and HPV18 being the most prevalent high-risk types worldwide (8,25).Women who have tested positive for high-risk HPV tend to harbor abnormal cervical cytology, and some studies have reported a correlation between viral load and disease severity (19,20,24,28,31). However, the consistency of these findings has been questioned, and it is now realized that the relationship is a lot more complex (5-7, 35). As the severity of disease increases, HPV is often found integrated into the host genome, making the interpretation of viral load even more complex. Furthermore, the available viral load data have been generated using different methodologies that may not be directly comparable (13,17,28,29).The HPV genome can exist in two physical forms: a closed circular episomal form or linearized and integrated into the host genome. Integration of the viral genome is often associated with the disruption of the E2 gene, which has regulatory control of the oncogenes E6 and E7. Nevertheless, this concept has been questioned by a recent study where the integration of the HPV16 genome was not necessarily associated with the overexpression of E6 and E7 (14). HPV18 has been found to be strongly associated with adenocarcinoma of the cervix. Studies carried out with HPV18 have shown that the viral genome is almost invariably found to be integrated in highgrade cervical intraepithelial lesions and invasive cancers (2,9,22,27,32), and these findings potentially allow the us...

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Section: Discussionmentioning

confidence: 94%

Analysis of Human Papillomavirus Type 18 Load and Integration Status from Low-Grade Cervical Lesion to Invasive Cervical Cancer

Cheung¹,

Cheung²,

Ng³

et al. 2009

J Clin Microbiol

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“…Some studies have shown a positive association between viral load and the severity of cervical lesion [18][19][20]. However, the biological explanation remains obscure.…”

Section: Discussionmentioning

confidence: 99%

Viral Load, E2 Gene Disruption Status, and Lineage of Human Papillomavirus Type 16 Infection in Cervical Neoplasia

Cheung¹,

Lo²,

Cheung³

et al. 2006

J INFECT DIS

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The clinical utility of human papillomavirus (HPV) load and integration status remains unclear. We applied refined methods to delineate the viral load, integration status, and lineage of 104 women with HPV-16 monotype infection, including 19 with normal cervices, 9 with histologically proven cervical intraepithelial neoplasia (CIN) 1, 24 with CIN 2, 27 with CIN 3, and 25 with squamous cell carcinoma (SCC). Higher crude viral load, as determined by real-time polymerase chain reaction (PCR) targeting the E7 gene, was observed for SCC but became insignificant after normalization for cell content. Integration was located and quantified by real-time PCRs targeting, respectively, the carboxyl, amino, and hinge domains of the E2 gene. Pure episomal, integrated, and mixed forms were observed in all disease groups. Most E2 gene disruptions involved the amino-terminal, but sparing the hinge region that has been frequently used as a surrogate marker of integration. Large-fragment disruption involving all 3 E2 regions was observed only in the CIN 3 and SCC groups. Altogether, 33.3% of the CIN 3 group and 28.0% of the SCC group harbored pure episomal genomes. The Asian lineage was associated with a higher risk for CIN 3/SCC than the European lineage, and 6 of the 7 large-fragment E2 disruptions were from Asian lineage. The link between viral lineage, integration pattern, and oncogenesis deserves further study.

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“…Previous studies have shown that the detection of high-risk HPV types indicates a higher risk of an existing high-grade lesion [Mansell et al, 1994;Herrero et al, 2000]. The extent to which the presence of high-risk HPV may increase the risk of developing high-grade lesions in women with mildly abnormal smears remains unclear.…”

Section: Introductionmentioning

confidence: 97%

Human papillomavirus DNA detection in the management of women with twice mildly abnormal cytological smears

Terry

Londesborough

et al. 2002

Journal of Medical Virology

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This study was undertaken to investigate the value of HPV testing in women referred with two abnormal smears that were graded as mild dyskaryosis or less who attended for at least three follow-up visits. One hundred forty-nine women were included in the study and a total of 39 high-grade lesions including one cancer were detected. All of these were found to be associated with the persistent presence of one or more of 13 high-risk human papillomavirus types (HPV) as detected by a multiplex type specific PCR technique. Two high-grade lesions were initially missed by cytology. In contrast, no cytological or histological evidence of high-grade lesions was found during a follow-up period of up to 8 years in 62 women with no high-risk HPV infection or in 38 women with only transient high-risk HPV infection. The utility of high-risk HPV detection in the management of women presenting with mild cytological abnormalities is discussed.

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Semi‐quantitative human papillomavirus DNA detection in the management of women with minor cytological abnormality

Cited by 23 publications

References 12 publications

Analysis of Human Papillomavirus Type 18 Load and Integration Status from Low-Grade Cervical Lesion to Invasive Cervical Cancer

Analysis of Human Papillomavirus Type 18 Load and Integration Status from Low-Grade Cervical Lesion to Invasive Cervical Cancer

Viral Load, E2 Gene Disruption Status, and Lineage of Human Papillomavirus Type 16 Infection in Cervical Neoplasia

Human papillomavirus DNA detection in the management of women with twice mildly abnormal cytological smears

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