Human papillomavirus genotyping and p16INK4a expression in cervical intraepithelial neoplasia of adolescents

Abstract

Adolescents have high rates of human papillomavirus (HPV) infection, and persistent high-risk HPV infection can lead to the development of cervical cancer. The cyclin-dependent kinase inhibitor, p16 INK4a is overexpressed in cervical intraepithelial neoplasia (CIN), probably due to a persistent and integrated HPV infection. This study investigated p16 INK4a expression, grades of CIN, and high-risk HPV infection in adolescent cervical biopsies. Biopsies were immunohistochemically stained for p16 INK4a . The presence of wide-spectrum, low-risk, or highrisk HPV was determined by amplifying DNA extracted from the cervical biopsies. Early sexual activity with multiple partners places many female adolescents at high risk for the future development of cervical cancer. The prevalence of human papillomavirus (HPV) infection in adolescents ranges from 19 to 46%, but the cervical intraepithelial neoplasia (CIN) in adolescents are predominantly low-grade and in the great majority of cases they resolve spontaneously. Only 0.12-3% of adolescents known to be infected with high-risk HPV develop high-grade CIN, and cervical carcinoma is extremely rare. 1-5 Woodman et al 4 reported that adolescents infected with HPV 16, 18, and 31 had a higher risk of developing high-grade CIN than persons infected with other oncogenic HPV types. Moscicki et al 6 observed that persistently positive high-risk HPV testing precedes the development of high-grade CIN.High-risk HPV DNA can be detected in almost all high-grade CIN and cervical cancers. 7,8 From a screening study of 7932 women aged 21-30 years, Clavel et al 9 reported that 23% had high-risk HPV infections. For the majority of women, the infections are transient and last 8-10 months. 9-11 It was the repeated positive high-risk HPV test results, reflecting persistent infection that predicted a likelihood of having a high-grade CIN. 3,9 In susceptible adolescents, either repeated exposure or an inability to suppress immunologically an infection may promote the oncogenic potential of

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

“…We found that the distribution patterns of the individual HPV types differed from those shown by a pooled data from North American population and by our previous study in Mississippi, which showed HPV 16 to be the most prevalent, followed by HPV 18 and 31. 8,37 In our current study, HPV 16 was the most prevalent type, followed by HPV 31 and HPV 35. HPV 18 was under-represented in our carcinoma and CIN 2/3 groups.…”

The Indicators of Predicting Disease Outcome in HPV Carcinogenesis

“…Most studies confirm p16 overexpression in all HSIL lesions but also in some normal epithelium of cervix at both protein (von Knebel Doeberitz et al, 2002) and messenger levels (Bleotu et al, 2009). On the other hand, p16 is not expressed in cervicitis nor is in squamous metaplasic epithelium (in the absence of CIN stages) (Hu et al, 2005). Still, other studies proved that p16 high level was found in cervical glandular epithelium and also in metaplasic epithelium.…”

Evaluation of a new p16INK4A ELISA test and a high‐risk HPV DNA test for cervical cancer screening: Results from proof‐of‐concept study

“…2,3 Some authors have proposed that p16 INK4a staining could be used to triage women with low-grade cytology results and predict who is more likely to have CIN3 or worse. 4,5 HPV transformed cells with high levels of p16 INK4a can be identified with a protein-based assay. Thus, a biochemical test for p16 INK4a might be better than a test for high-risk HPV DNA at identifying the subset of HPV-infected women with significant clinical disease.…”

“…Staining of histology and cytology specimens for p16 INK4a has shown that detection of antibodies to the protein is a sensitive and specific marker of high-grade cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. [2][3][4][5] In a number of studies, p16 INK4a staining of biopsy tissue was seen in over 90% of cases with high-grade CIN and invasive cervical cancer, being generally absent from the normal tissue and staining only zonal or patchy areas of the low-grade CIN cases. 2,6,7 Findings from these immunostaining studies suggest that compared to high-risk HPV DNA, which is detected in the majority of both high-and low-grade lesions, 8 p16 INK4a might be a better marker for identifying those lesions most likely to progress.…”