Association between human papillomavirus DNA load and development of cervical intraepithelial neoplasia and cervical cancer

Huang, Yi; Huang, Meng; LI, X.-G.; LI, N.; Li-ping, WU

doi:10.1111/j.1525-1438.2007.01092.x

Cited by 12 publications

(9 citation statements)

References 31 publications

(60 reference statements)

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“…For CIN, the effect of alcohol consumption was examined for CIN1 and CIN2/3 subgroups respectively [8], [11]–[13]. HPV viral load was categorized into three groups: high (≥100 RLU/PC), medium (10–100 RLU/PC), and low (<10 RLU/PC) [14]–[17].…”

Section: Methodsmentioning

confidence: 99%

Alcohol Consumption and Viral Load Are Synergistically Associated with CIN1

Min

Lee

et al. 2013

PLoS ONE

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PurposeWe investigated the association between alcohol consumption and risk of cervical intraepithelial neoplasia (CIN) and cervical cancer, and determined whether these associations were modified by human papillomavirus (HPV) viral load in high-risk HPV-positive women participating in the Korean HPV cohort study (KHPV).MethodsAmong the women recruited in the KHPV (n = 1,243) from March 2006 to December 2009, we analyzed normal cytology (n = 581) as control group, CIN1 (n = 299), CIN2/3 (n = 161), or cervical cancer (n = 202). Multinomial logistic analysis was performed to estimate multivariate-adjusted odds ratios (OR).ResultsAlcohol drinkers had an increased risk of CIN1 (OR = 2.18, 95% CI 1.22–3.89) compared with non-drinkers after adjusting for potential confounders. Subjects with more frequent alcohol consumption had a higher risk of CIN1 (p for linear trend <0.0001). Higher ethanol consumption was associated with an increased risk of CIN1 (p for linear trend = 0.0001). We also observed a synergistic effect between HPV viral load and alcohol consumption: drinkers with a high HPV viral load (≥100 RLU/PC) were associated with a significantly increased risk of CIN1 (OR = 19.1; 95% CI, 6.60–55.3, interaction p<0.001). There were no associations between alcohol drinking and CIN2/3 or cervical cancer.ConclusionsHPV viral load and alcohol was associated with the risk of CIN1 among high-risk HPV-positive women. This is the first demonstration that alcohol is an independent and combined risk factor of CIN1.

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Section: Methodsmentioning

confidence: 99%

Alcohol Consumption and Viral Load Are Synergistically Associated with CIN1

Min

Lee

et al. 2013

PLoS ONE

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“…Many studies that attempted to examine viral load associations did not analyze the physical status of the viral genome (4,12,13,18,28,29). In addition, some studies have used a method that measured the total viral load of a mixture of HPV types (13,18,28,29). It is now known that the relationship between viral load, integration, and disease severity varies with different HPV types (5)(6)(7).…”

Section: Discussionmentioning

confidence: 99%

“…As the disease worsens, the virus becomes integrated, which is a genome form not capable of self-replicating, and therefore the mechanism for maintaining a high viral load is uncertain. Many studies that attempted to examine viral load associations did not analyze the physical status of the viral genome (4,12,13,18,28,29). In addition, some studies have used a method that measured the total viral load of a mixture of HPV types (13,18,28,29).…”

Section: Discussionmentioning

confidence: 99%

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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“…High viral levels may increase the risk of carcinogenic progression, but studies to date have been inconclusive [Wang and Hildesheim, 2003]. Previous studies have tended to report positive associations between HPV viral load and presence/increasing grade of cervical squamous intraepithelial lesions (SIL) or cervical intraepithelial neoplasia (CIN), but most have been cross-sectional in design [Forslund et al, 1997;Ikenberg et al, 1997;Ho et al, 1998aHo et al, , 2006Swan et al, 1999;Healey et al, 2001;Sun et al, 2001Sun et al, , 2002Zerbini et al, 2001;Wang-Johanning et al, 2002;Gravitt et al, 2003;Hernandez-Hernandez et al, 2003;Santos et al, 2003;Hesselink et al, 2004;Lillo et al, 2005;Lo et al, 2005;Rajeevan et al, 2005;Tsai et al, 2005;Carcopino et al, 2006;Flores et al, 2006;Lai et al, 2006;Oikonomou et al, 2006;Snijders et al, 2006;Wu et al, 2006;Cricca et al, 2007;Fiander et al, 2007;Huang et al, 2007] and/or measured viral load in ways that were only semiquantitative or not type-specific [Ikenberg et al, 1997;Ho et al, 1998a;Healey et al, 2001;Sun et al, 2001Sun et al, , 2002Zerbini et al, 2001;Castle et al, 2002;Dalstein et al, 2003;Hernandez-Her...…”

Section: Introductionmentioning

confidence: 99%

Quantitative human papillomavirus 16 and 18 levels in incident infections and cervical lesion development

Harris

Jansen³

et al. 2009

Journal of Medical Virology

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Human papillomavirus (HPV) RNA levels may be a more sensitive early indicator of predisposition to carcinogenesis than DNA levels. We evaluated whether levels of HPV-16 and HPV-18 DNA and messenger RNA (mRNA) in newly detected infections are associated with cervical lesion development. Female university students were recruited from 1990-2004. Cervical samples for HPV DNA, HPV mRNA, and Papanicolaou testing were collected tri-annually, and women were referred for colposcopically-directed biopsy when indicated. Quantitative real-time polymerase chain reaction of L1 and E7 DNA and E7 mRNA was performed on samples from women with HPV-16 and HPV-18 infections that were incidently detected by consensus PCR. Adjusting for other HPV types, increasing E7 cervical HPV-16 mRNA levels at the time of incident HPV-16 DNA detection were associated with an increased risk of cervical intraepithelial neoplasia grade 2 to 3 (HR per 1 log10 increase in mRNA=6.36,95%CI=2.00-20.23). Increasing HPV-16 mRNA levels were also associated with an increased risk of cervical squamous intraepithelial lesions; the risk was highest at the incident positive visit and decreased over time. Neither HPV-16 E7 DNA levels nor HPV-18 E7 DNA nor mRNA levels were significantly associated with cervical lesion development. Report of >1 new partner in the past 8 months (relative to no new partners) was associated with increased HPV mRNA (viral level ratio [VLR]=10.05,95%CI=1.09-92.56) and increased HPV DNA (VLR=16.80,95%CI=1.46-193.01). In newly detected HPV-16 infections, increasing levels of E7 mRNA appear to be associated with an increased risk of developing cervical pre-cancer.

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Association between human papillomavirus DNA load and development of cervical intraepithelial neoplasia and cervical cancer

Cited by 12 publications

References 31 publications

Alcohol Consumption and Viral Load Are Synergistically Associated with CIN1

Alcohol Consumption and Viral Load Are Synergistically Associated with CIN1

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

Quantitative human papillomavirus 16 and 18 levels in incident infections and cervical lesion development

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