Abstract
This study was conducted to assess the predictive value of p-glycoprotein (p-gp) and p53 immunoexpression in human papillomavirus (HPV) infected cases of cervical dysplasia. Expression of both p-gp and p53 proteins was detected in cervical smears from 177 squamous intraepithelial lesions (SIL) cases along with 183 "atypical squamous cells of unknown significance" (ASCUS) and 150 normal cases. HPV 16 and 18 infection was detected by polymerase chain reaction using type-specific primers for HPV sub-types. There were no significant detectable p53 and p-gp expression in the normal cervix smears (p>0.05). In the ASCUS group 10 cases were positive for both p53 and p-gp immunoreactivity. In cervical dysplasia cases, p53 was positive in 86 (48.58%) while p-gp was positive in 93 (52.54%) and the two markers showed a highly significant correlation (r=0.92, p<0.001). Expression of p53 and p-gp was associated with grade of SIL (p<0.001). A positive correlation between the presence of HPV and expression of proteins p53 and p-gp in smears of patients with cervical lesions was also noted (p<0.001). Thus, p53 and p-gp immunostaining in cervical smears may act as an auxiliary biomarker for detection of HPV-associated cervical lesions. Additionally, a significant positive correlation between ascending grades of SIL and labeling indices of markers suggests that p53 and p-gp can be used as an adjunct to cytomorphological interpretation of conventional cervical Pap smears.
Highlights
Cancer of the uterine cervix is the second most common and the fifth most deadly cancer among women worldwide, and it is the principal cancer among women in most developing countries (Kent, 2010)
human papillomavirus (HPV)-DNA detection in cervical smears by PCR showed that 92% cases in normal and in 85% cases in atypical squamous cells of unknown significance” (ASCUS) were negative for HPV presence (Table-1)
Among the HPV positive cases, distribution of HPV subtypes was similar in the ASCUS, squamous intraepithelial lesions (SIL) and CIS groups, with the majority being positive for HPV 16 subtype i.e. 55%, 57% and 77% cases, respectively
Summary
Cancer of the uterine cervix is the second most common and the fifth most deadly cancer among women worldwide, and it is the principal cancer among women in most developing countries (Kent, 2010). With an overall poor survival rate cervical cancer continues to remain a key international health problem (Ferlay et al, 2002). Accomplishment of Papanicolaou (Pap) screening program to reduce the incidence of cervical cancer is successful among the developed nations (Canavan and Doshi, 2000). The extent of cervical cancer incidence reduction and the cost-effectiveness of such programs still remains the subject of debate in most of the developing countries. Due extremely variable natural history of cervical intraepithelial neoplasia (CIN), till date it is not possible to predict which cases of CIN will progress and which will persist or regress. Objective biomarkers which allow unambiguous identification of truly dysplastic cells and/or predict disease progression is required
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