The Significance of Human Papillomavirus Viral Load in Prediction of Histologic Severity and Size of Squamous Intraepithelial Lesions of Uterine Cervix

Sun, Chien An; Lai, Hung Cheng; Chang, Cheng‐Chang; Neih, Sin; Yu, Cheng; Chu, Tang-Yuan

doi:10.1006/gyno.2001.6336

Cited by 108 publications

(94 citation statements)

References 19 publications

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“…In our study, we preselected women with single type infections. However, meanwhile we have collected preliminary data of cervical scrapings containing multiple infections including HPV 16,18 and/or 31 and corresponding biopsies of some women with underlying CIN lesions. It appeared that in this biopsy series only one of the HPV types present in the paired scrape could be detected by GP51/61-PCR.…”

Section: Discussionmentioning

confidence: 99%

“…6 In this context, it has been demonstrated for HPV 16 infections that increased viral loads would be associated with an increased risk of CIN 2 whereas reduced amounts of viral DNA reflects the absence of CIN lesions or viral clearance, which is associated with regression of CIN lesions. 7 Still, data in favor of viral load being informative for risk of CIN 2 are mainly based on HPV 16, whereas those of hrHPV types other than HPV 16 are limited and inconsistent, [8][9][10][11][12][13][14][15][16][17][18][19] obviously because of the generally low numbers of women with non-HPV 16 types studied so far. Moreover, the potential value of viral load assessment is quite likely to be dependent on the method used to define HPV positivity since its impact seems lower when the hybridization-based hybrid capture 2 (hc2) is used to define HPV positivity when compared with PCR-based assays, which generally display a higher analytical sensitivity.…”

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confidence: 99%

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Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16, 18, 31 and 33‐positive women with normal cytology

Snijders

Hogewoning

Hesselink

et al. 2006

Intl Journal of Cancer

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An increased high-risk human papillomavirus (hrHPV) viral load in cervical scrapings has been proposed as a determinant for highgrade cervical intraepithelial neoplasia (CIN) and cervical cancer ( CIN 2), but data so far for HPV types different from HPV 16 are limited and inconsistent. In addition, a viral load threshold to distinguish hrHPV positive women without CIN 2 still has not been defined. Here, we used baseline cervical scrapings of women with normal cytology participating in a large population-based cervical screening trial (i.e. POBASCAM) who were GP51/61-PCR positive for 4 common hrHPV types, i.e. HPV 16, 18, 31 or 33, as a reference to arbitrarily define various viral load thresholds (i.e. 25th, 33rd, 50th, 67th and 75th percentiles of the lowest viral load values) for distinguishing women having single infections with these types without high-grade CIN. Viral load assessment was performed by real time type-specific PCR. The viral load threshold values were subsequently validated on abnormal cervical scrapes of 162 women with underlying, histologically confirmed CIN lesions containing 1 of these 4 hrHPV types. All 59 women with CIN 3 had viral load levels that were higher than those of 33% of the women with normal cytology containing the respective hrHPV type detectable by GP51/61-PCR (i.e. higher than the 33rd percentile of viral load). By using this 33rd percentile viral load cut-off, sensitivity for CIN 3 of 100% (95% CI 93.9-100) was obtained. Hence, application of this viral load threshold would increase the specificity of HPV testing for HPV 16, 18, 31 and 33-associated prevalent CIN 3 without the cost of a marked reduction in sensitivity. In practice, on the basis of viral load analysis, a less aggressive management can be foreseen for 33% of the women with normal cytology participating in a population-based screening program who are GP51/61-PCR positive for HPV 16, 18, 31 or 33. ' 2006 Wiley-Liss, Inc. Key words: HPV; viral load; CIN; real time PCRThe relationship between high-risk human papillomavirus (hrHPV) infection and cervical cancer has become evident from epidemiological and functional studies. 1-3 hrHPV DNA has been detected in almost all cervical squamous cell carcinomas and adenocarcinomas. This finding has led to the widely accepted concept that hrHPV infection is a necessary cause of cervical cancer. [1][2][3] The close association between hrHPV and cervical cancer has resulted in the use of hrHPV testing on cervical scrapes for the detection of cervical cancer and its precursor stages. Several studies have shown that addition of hrHPV testing to cervical cytology improves the sensitivity and negative predictive value for highgrade cervical intraepithelial neoplasia (CIN) and cervical cancer ( CIN 2) compared with cytology alone. 4,5 However, the positive predictive value of the hrHPV test is relatively low because many hrHPV positive women will clear the virus. Especially, hrHPV positive women with cytomorphologically normal smears fall in this category. As a consequence, seve...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16, 18, 31 and 33‐positive women with normal cytology

Snijders

Hogewoning

Hesselink

et al. 2006

Intl Journal of Cancer

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“…27 The HPV genotype strip contains 29 probe lines, detecting 27 individual HPV genotypes and two concentrations of the b-Globin control probe (All reagents were kindly provided by Roche Molecular Systems, Alameda, CA). The following types were detected: 6,11,16,18,26,31,33,35,39,40,42,45, 51 to 59, 66, 68, 73, 82, 83 and 84.…”

Section: Hpv Genotypingmentioning

confidence: 99%

“…Using a semi-quantitative measure of HPV16 DNA levels, several observational studies have found a high correlation between high viral load and high-grade intra-epithelial lesions. [11][12][13][14] In a cohort study Josefsson et al found that persistent infection with HPV16 along with high viral load values was a risk factor for the development of cervical cancer. 15 Ylitalo et al observed that persistently high viral load values correlated with the progression of cervical dysplasia.…”

mentioning

confidence: 99%

Cross‐sectional analysis of oncogenic HPV viral load and cervical intraepithelial neoplasia

Flores

Papenfuss

Klimecki

et al. 2005

Intl Journal of Cancer

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In human papillomavirus (HPV)-associated carcinogenesis, HPV infection characteristics such as viral load may play an important role in lesion development. The purpose of this study was to determine the association between quantitative assessment of oncogenic HPV viral load, and abnormal cytology among women residing along the United States-Mexico border. A cross-sectional study of 2,319 women was conducted between 1997 and 1998. Viral load of oncogenic HPV types (16,18,31,39, 45, 51, 52, and 58) was measured among 173 HPV (1) women using quantitative real-time PCR. Overall, HPV 16, 31, 52 and 58 showed the highest viral load. Single type infection had higher viral loads compared to multiple type infections. HPV viral load declined significantly (p 5 0.04) with age. No significant association was observed with other known HPV risk factors such as oral contraceptive use, parity, sexual and STD history. Viral load was independently associated with degree of cervical lesions. An adjusted odds ratio (AOR) of 4.7 for the association between increasing total viral load and Atypical Squamous Cells of Undetermined Significance (ASCUS)/ Atypical Glandular Cells of Undetermined Significance (AGUS) was observed (p for trend <0.01). Increased risk of low-grade SIL was observed with higher viral load compared with HPV negative women (AOR 5 47.7 for total viral load; AOR 5 37.1 for HPV viral load not including HPV16, and AOR 5 25.9 for HPV16 viral load). Likewise, increased risk of high-grade SIL with higher viral loads was observed (AOR 5 58.4 for high total viral load compared with HPV negative women, AOR 5 58.1 for HPV viral load not including HPV16, and AOR 5 69.8 for HPV16 high viral load). Results from this study suggest a dose-response relationship between increasing oncogenic HPV viral load and risk of LSIL and HSIL. ' 2005 Wiley-Liss, Inc.Key words: human papillomavirus; viral load; cervical lesions Squamous intraepithelial lesions (SIL) are the precursor lesions for the development of cervical cancer and are caused primarily by infection with human papillomavirus (HPV). Cervical cancer, however, does not occur without the persistent presence of HPV in the squamo-columnar junction. 1 Since the majority of cervical lesions regress to normal cytology after a period of 12 months from presumed first infection, it is thought that the remaining cervical lesions persist due to environmental, host and viral cofactors that have a pleiotropic effect on HPV viral replication, the immune system and tissue microenvironment. [2][3][4][5][6][7][8][9][10] Recent studies suggest that HPV16 viral load may be a possible molecular biomarker in the natural history of HPV infection. Using a semi-quantitative measure of HPV16 DNA levels, several observational studies have found a high correlation between high viral load and high-grade intra-epithelial lesions. Although a possible role for HPV16 viral load has emerged, only a few studies have used quantitative measures of viral load to study the association of distinct oncogenic HPV types a...

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“…In contrast, two other studies using Hybrid Capture assays revealed smaller amounts of viral DNA in cervical samples of women with HSIL compared to those with LSIL (Farthing et al, 1994;Sun et al, 1995). Sun et al (2001) recently revealed that the effect of HPV infection on SIL development is dominated by the viral load, thus highlighting a potential application of viral load testing in predicting the advancement of cervical intraepithelial lesions. Ylitalo et al (2000) reported that CIN3 is associated with HPV-16-positive women who have consistently high viral loads, and Sherman et al (2002) concluded that for women with ASCUS, HPV-load testing is highly sensitive for detecting CIN3 and cancer with dramatically fewer referrals for colposcopy.…”

Section: Discussionmentioning

confidence: 93%

Clinical and economic benefit of HPV-load testing in follow-up and management of women postcone biopsy for CIN2–3

et al. 2003

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This study aimed to evaluate the clinical and economic implications of integrating human papilloma virus (HPV) load testing into the follow-up and management protocol of women postconisation for high-grade cervical intraepithelial neoplasia (CIN2 -3). We evaluated 130 suitable women: 63 were screened biannually by Pap smears ('conventional approach') and 67 also had HPV-load testing ('HPV approach'). More stringent criteria for undergoing colposcopy or reconisation were observed by the former group compared to the latter. Both approaches were analysed for cost effectiveness. There were 33 out of 67 (49.2%) colposcopic referrals and 24 out of 67 (35.8%) reconisation/hysterectomies with the 'conventional approach' compared to 9 out of 63 (14.2%) and 7 out of 63 (11.1%) with the 'HPV approach'. Cervical intraepithelial neoplasia 2 -3 residual disease was detected in 7 out of 67 (10.5%) and 7 out of 63 (11.1%) women. The 'conventional approach' had more negative colposcopic biopsies and more negative reconisation/hysterectomy histologies than the 'HPV approach'. The respective cost per detection of one case of residual disease was US$3573 and US$3485. The 'HPV approach' required fewer colposcopic and reconisation procedures to detect one case of residual CIN2 -3. Its higher positive predictive value than that of cytology provided a significant decrease in false positive rates and a reduction of US$88 per detected case.

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The Significance of Human Papillomavirus Viral Load in Prediction of Histologic Severity and Size of Squamous Intraepithelial Lesions of Uterine Cervix

Cited by 108 publications

References 19 publications

Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16, 18, 31 and 33‐positive women with normal cytology

Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16, 18, 31 and 33‐positive women with normal cytology

Cross‐sectional analysis of oncogenic HPV viral load and cervical intraepithelial neoplasia

Clinical and economic benefit of HPV-load testing in follow-up and management of women postcone biopsy for CIN2–3

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