Human papillomavirus 16 load in normal and abnormal cervical scrapes: An indicator of CIN II/III and viral clearance

Abstract

The relation between human papillomavirus type 16 (HPV 16) viral load in cervical scrapes and development of highgrade cervical intraepithelial neoplasia (CIN II or III) was studied in a nested case-control study of women with normal cytology (group A) and in a cohort of women with abnormal cytology (group B). HPV 16 DNA load was determined using a quantitative real-time PCR assay. In group A, case women (women with CIN II/III, n ‫؍‬ 12) had a significantly higher viral load than control women (women with CIN < I, n ‫؍‬ 47). This resulted in an increased relative risk of women with the 50% highest viral load for development of CIN II/III (OR 7.7; CI 1.6 -33). In group B, women with CIN II/III (n ‫؍‬ 38) had a significantly higher viral load than women with CIN < I (n ‫؍‬ 25). Women with the 50% highest viral load had an increased relative risk of CIN II/III (OR 3.2; CI 1.1-9.3) and a decreased chance of both viral clearance and cytologic regression. Our data suggest that in women with normal cytology an increased HPV 16 load confers an increased risk of developing a CIN lesion. A sustained high viral load is subsequently informative for progression to a high-grade CIN lesion. © 2002 Wiley-Liss, Inc. Key words: HPV 16 load; normal cytology; abnormal cytology; CIN II/III; viral clearanceA multitude of studies have established infection with high-risk human papillomavirus (HPV) types as a necessary cause of cervical cancer. 1,2 On the basis of these studies, it has been proposed that testing for the presence of high-risk HPV DNA in cervical scrapes as an adjunct of cervical cytology can be of great value in a variety of clinical settings. 3 Persistence of high-risk HPV DNA appeared to be a prerequisite for the development of high-grade CIN lesions. 4,5 Nevertheless, the far majority of high-risk HPV infections are transient and will either not give rise to a lesion or at most lead to spontaneously regressing, low-grade cervical intraepithelial neoplasia (CIN). 6,7 Hence, there is a strong need for additional markers that predict the outcome of high-risk HPV infection with increased specificity. Using semiquantitative approaches, several studies have implicated that the amount of highrisk HPV DNA present in the cervical scrape, the viral load, can be of value to predict prevalent or incident high-grade CIN. 8 -16 This has recently been substantiated by a fully quantitative, real-time PCR-based retrospective study on cytomorphologically normal archival smears of women who developed cervical carcinoma in situ (CIS). It appeared that women with the highest HPV 16 load were at increased risk of developing CIS. 17 However, with the aid of a fully quantitative method, no studies so far have addressed whether viral load could also be informative for women with abnormal cervical scrapes or to predict future clearance of high-risk HPV infections. Using frozen, freshly collected cervical scrapes collected from well-defined cohorts of women with normal 18,19 and abnormal cytology, 5 we addressed the following questions. First...

HPV16 semiquantitative viral load and serologic biomarkers in oral and oropharyngeal squamous cell carcinomas

“…Large studies on cervical smears suggested that persistent HPV infection, 21 cytological progression, [21][22][23][24] and the risk of a highgrade cervical lesion [21][22][23][24][25] are each associated with high HPV viral load in the cervix. As a consequence, viral load assessment was proposed to distinguish clinically relevant HPV infections in the cervix, 26 yet has only been assessed in a few studies of sites beyond the cervix.…”

Human papillomavirus DNA load and p16INK4aexpression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy

“…To test the quantity and quality of the extracted DNA and to demonstrate that the samples were free of inhibitory substances, real-time beta-globin gene PCR was performed on all samples as previously described. 25 HPV16 DNA load (VL) was determined in HPV16-positive samples and was defined as HPV16 copies per beta-globin gene copy. HPV16 copy numbers were determined by HPV16-specific quantitative real-time PCR (amplimer length 88 bp) using a LightCycler 480 (Roche, Mannheim, Germany), basically described before.…”

High viral loads of human papillomavirus predict risk of invasive cervical carcinoma

“…Viral load has been suggested as a marker of nontransient infection, and high HPV load in smears with normal cytology has been associated with the risk of developing dysplasia and carcinoma in situ (CIS) van Duin et al, 2002;Dalstein et al, 2003;Moberg et al, 2004). However, it is not known whether high viral load is also predictive of invasive cervical cancer, as past studies have pooled the outcomes of invasive cancers together with earlier stages of the disease (Lorincz et al, 2002;Sherman et al, 2002Sherman et al, , 2003Sun et al, 2002;Dalstein et al, 2003;Gravitt et al, 2003).…”