High levels of HPV-16 DNA are associated with high-grade cervical lesions in women at risk or infected with HIV

Fontaine, Julie; Hankins, Catherine; Mayrand, Marie‐Hélène; Lefevre, Jonas; Money, Deborah; Gagnon, Simon; Rachlis, Anita; Pourreaux, Karina; Ferenczy, Alex; Coutlée, François

doi:10.1097/01.aids.0000168972.65304.6b

Cited by 37 publications

(42 citation statements)

References 53 publications

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“…HPV viral load seems to be a promising marker for high-grade cervical disease (11,12). We found that higher HPV viral loads were associated with high-grade histology (for HPV 16) and high-grade cytology (for HPV 16, 18, and 31).…”

Section: Discussionmentioning

confidence: 71%

“…However, as with cervical pathology, there is considerable interobserver variability in the interpretation of anal cytology and histopathology (9), and different interpretations of anal squamous lesions may critically affect management decisions. The detection of human papilloma virus (HPV) -related biomarkers in cervical pathology specimens may be helpful in determining the cytologic and histologic diagnostic categories of premalignant and malignant lesions (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

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Screening for HIV-Associated Anal Cancer: Correlation of HPV Genotypes, p16, and E6 Transcripts with Anal Pathology

Salit

Tinmouth

Chong

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: HIV-positive men with a history of analreceptive intercourse are at risk for anal cancer. We determined whether human papilloma virus (HPV) biomarkers were correlated with anal pathology in these men. Methods: HPV genotype was determined by PCR/line blot assay. Real-time PCR assays were done for viral load, E6 transcripts for HPV genotypes 16, 18, and 31, and p16 transcripts. Results: The most common oncogenic HPV types were HPV 16 (38%), 18 (19%), 45 (22%), and 52 (19%). HPV types 16, 18, 31, 52, 59, and 68 were associated with highgrade histology. The number of HPV genotypes per anal swab was higher for anal intraepithelial neoplasia (AIN) 2/3 than for normal or AIN 1 histology [median, 5 types (interquartile range) (IQR), 3-7 versus 3.5 (IQR), 2-6; P = 0.0005]. HPV 16 viral load was also associated with

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Screening for HIV-Associated Anal Cancer: Correlation of HPV Genotypes, p16, and E6 Transcripts with Anal Pathology

Salit

Tinmouth

Chong

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…In previous studies, a high viral load of HPV 16 was reported to be associated with persistent infection and the development of CIN 2/3 and cervical carcinoma 11,12,16,30,46 and might have predictive value for CIN 2/3 or carcinoma. 14,42,47,48 Most studies using qRT-PCR assays in cytology specimens have demonstrated an increased HPV 16 viral load in higher-grade squamous intraepithelial lesions.…”

Section: Discussionmentioning

confidence: 92%

“…Similar observations have also been made in cytology specimens, which makes it difficult to define a cutoff value for risk prediction. 30,51 Our cross-sectional data also limit the evaluation of kinetics of the HPV 16 viral load, which may be more valuable in predicting CIN 2/3 and cervical carcinoma, as demonstrated in longitudinal studies that a higher viral load is highly predictive for precancerous lesion progression. 12,15 Periodic evaluation of the HPV viral load may be useful in monitoring viral clearing and predicting cervical precancerous lesion progression, but requires more studies to determine the value of HPV viral load as a predictive marker.…”

Section: Discussionmentioning

confidence: 99%

“…22 The evaluation of HPV 16 integration using qRT-PCR can also be affected by the quantity of the episomal form of the virus in specimens. 22 Nevertheless, Given the fact that the mixed integrated and episomal forms of HPV 16 are the predominant pattern in CINs or even normal cervix, 30,34,42,44,45 the relative ratio of E2/E6, instead of the prevalence of completely integrated HPV 16, may be more specific in predicting CIN progression and may have potential as a predictive marker. However, our small sample size in a cross-sectional study precludes any conclusion about the use of the HPV 16 E2/E6 ratio cutoff to predict CIN progression.…”

Section: Discussionmentioning

confidence: 99%

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Distribution and viral load of eight oncogenic types of human papillomavirus (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and carcinoma

et al. 2007

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Current human papillomavirus (HPV) DNA testing using pooled probes, although sensitive, lacks specificity in predicting the risk of high-grade cervical intraepithelial neoplasia (CIN 2/3) progression. To evaluate selected HPV genotyping, viral load, and viral integration status as potential predictive markers for CIN progression, we performed HPV genotyping in formalin-fixed, paraffin-embedded cervical tissue with cervical carcinoma (29 cases) and CINs (CIN 1, 27 cases; CIN 2, 28 cases; CIN 3, 33 cases). General HPVs were screened using consensus primers GP5 þ /GP6 þ and PGMY09/11. HPV genotyping and viral load measurement were performed using quantitative real-time PCR for eight oncogenic HPV types (16, 18, 31, 33, 35, 45, 52, and 58). HPV 16 viral integration status was evaluated by measuring HPV 16 E2/E6 ratio. We observed that HPV DNA positivity increased in parallel with the severity of CINs and carcinoma, with 59% positivity in CIN 1, 68% in CIN 2, 76% in CIN 3, and 97% in carcinoma (P trend ¼ 0.004). The eight oncogenic HPV types were significantly associated with CIN 2/3 (81%) and carcinoma (93%) (odds ratio (OR), 15.0; 95% confidence interval (CI), 5.67-39.76; Po0.0001) compared with the unknown HPV types (OR, 2.87; 95% CI, 0.89-9.22; P ¼ 0.08). HPV 16 was the predominant oncogenic HPV type in CIN 2/3 (51%) and carcinoma (71%) and integrated significantly more frequently in carcinoma than in CIN 2/3 (P ¼ 0.004). No significant differences in viral load were observed across the disease categories. Our findings suggest that selected genotyping for the eight oncogenic HPV types might be useful in separating women with a higher risk of CIN progression from those with a minimal risk. We also conclude that the HPV 16 integration status has potential to be a marker for risk assessment of CIN progression.

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Viral load of episomal and integrated forms of human papillomavirus type 33 in high‐grade squamous intraepithelial lesions of the uterine cervix

Khouadri

Villa

Gagnon

et al. 2007

Intl Journal of Cancer

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The association between total and integrated HPV-33 DNA loads and high-grade squamous intraepithelial lesions (HSIL) of the uterine cervix was investigated. Of 5,347 women recruited in 4 studies, 89 (64 without SIL, 7 low-grade SIL (LSIL), 15 HSIL, 3 unknown grade) were infected by HPV-33. HPV-33 E6, HPV-33 E2 and b-globin DNA were measured with real-time PCR that allowed to assess total (E6), episomal (E2) and integrated (E6-E2) HPV-33 viral loads. HPV-33 E6/E2 ratios 2.0 suggesting the presence of integrated HPV-33 were obtained for 28.6% (n 5 18) of women without SIL and 21.4% (n 5 3) of women with HSIL (p 5 0.74). Although median viral loads were similar, there was a trend toward having a greater proportion of women with HSIL in the fourth quartile (

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High levels of HPV-16 DNA are associated with high-grade cervical lesions in women at risk or infected with HIV

Abstract: Higher HPV-16 DNA loads are associated with cervical lesions detected by either histology or cytology. No additional information is gained by measuring integrated or episomal over total HPV-16 DNA loads.

Cited by 37 publications

References 53 publications

Screening for HIV-Associated Anal Cancer: Correlation of HPV Genotypes, p16, and E6 Transcripts with Anal Pathology

Screening for HIV-Associated Anal Cancer: Correlation of HPV Genotypes, p16, and E6 Transcripts with Anal Pathology

Distribution and viral load of eight oncogenic types of human papillomavirus (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and carcinoma

Viral load of episomal and integrated forms of human papillomavirus type 33 in high‐grade squamous intraepithelial lesions of the uterine cervix

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