Early integration of high copy HPV16 detectable in women with normal and low grade cervical cytology and histology

Abstract

Integrated HPV16 is present in low grade cervical lesions, mostly mixed with the episomal form. Women with the pure integrated form of HPV16 are older than those with the other forms.

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

“…36,39,40 Although the mechanism that causes persistent infection of HPV 16 is not completely clear, it has been reported to be associated with viral integration into the human genome. 41,42 In contrast, the oncogenic HPV types, such as HPV 52 and 58, was reported significantly less likely to be integrated into the cells of cervical carcinoma. 43 We demonstrated the integrated form of HPV 16 in all of the carcinoma specimens and significantly increased HPV 16 integration in cervical carcinoma compared with CIN 2/3, supporting the notion that HPV 16 integration into the host genome is an important step of carcinogenesis.…”

“…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.…”

“…17,18 In most published studies of cervical carcinoma, the integrated forms of HPV 16 were also observed in either all or a majority of the specimens. 42,43 AriasPulido et al 22 recently conducted a study of formalin-fixed paraffin-embedded as well as fresh cervical specimens using qRT-PCR and reported a relatively low proportion of the integrated type of HPV 16 in carcinoma in situ (30.3%) and in invasive carcinoma (60.9%). The discrepancies of HPV 16 integration in the published studies may be resulted by different primers targeting different E1 or E2 regions and the effect of the adjacent tissue around the targeted lesion.…”

“…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. However, a controversial observation has been reported, showing inconsistent results with significantly less HPV 16 viral load in high-grade squamous intraepithelial lesions than low-grade squamous intraepithelial lesions.…”

Diagnostic role of p16/INK4A protein in Human Papillomavirus (HPV) induced cervical dysplasia

“…The prevalence of the integrated HPV DNA sequence over episomal molecules then appears in a proportion of ASCUS graded smears (sometimes characterized by ASC-H cells) and in LSIL smears, but later on becomes clearly prevalent in HSIL grade smears and, of course, in cervical cancer. Women showing the prevalence of integrated HPV DNA were almost 10 years older than those with a predominating episomal HPV DNA pattern, which points to a higher risk of HPV infection in women aged over 35 years [20]. Three non-structural HPV coded oncoproteins are involved in host cell proliferation and immortalization (E5, E6 and E7) causing continuous host cell division rather than direct malignant transformation ( Table 3).…”