Expression of p16INK4a and human papillomavirus 16 with associated risk factors in cervical premalignant and malignant lesions

Abstract

Introduction:Human papilloma virus (HPV) which is causative factor for cervical cancer may interact with p16 leading to malignant transformation of cervical epithelial cells. The present study was conducted to assess the immunoexpression of p16 INK4a in premalignant and malignant lesions of cervix and to correlate it with HPV 16 expression. It was also intended to study the various risk factors which may be associated with cervical cancer in this north Himalayan region of India.Material and Methods:The study included 50 cases of premalignant and malignant cervical lesions and 50 controls diagnosed on histopathology over a period of one year. All the relevant clinical details were noted and both cases and controls were subjected to HPV 16 and p16 INK4a immunohistochemical staining.Results:67% of subjects (including cases and controls) and 94% of the cases were positive for HPV 16 expression. p16 INK4a expression was negative in all the controls, positive in 96% of invasive cancer, 66.6% in HSIL and 37.5% in LSIL.Conclusion:Cervical cancer is associated with low socio economic status, illiteracy, smoking, early age of marriage and conception in north Himalayan region of India. HPV 16 infection is positive in both cases and controls indicating high prevalence of HPV 16 in this region. Neoplastic transformation by HPV is identified by over expression of p16 INK4a in premalignant and malignant cases. The immunopositivity of p16 INK4a increases with the severity of cervical lesions and thus may play an important role in stratification of premalignant and malignant lesions.

Expression of Ki 67 and human papilloma virus 16 with risk factors in cervical pre malignant and malignant lesions

“…The present study also showed that HPV 16 is uniformly present in cervical premalignant and malignant lesions and there is no difference in its expression with severity of the lesion. This is in concordance with previous study by Zouheiret al who have also observed that there is no significant difference in HPV detection rate between HSIL (high grade squamous intraepithelial lesion) and LSIL (low grade squamous intraepithelial lesion) or between HSIL and cervical cancer [11]. In the present study, it was found that maximum number of cases (90%) were positive for Ki-67, amongst which 56% showed grade 3 positivity while all controls (100%) were negative for Ki-67 expression.…”

Absence of Nuclear p16 Is a Diagnostic and Independent Prognostic Biomarker in Squamous Cell Carcinoma of the Cervix

“…Importantly, we found that p16 expression-and especially the cytoplasmic/nuclear p16 ratio-significantly distinguished HSIL from SCCC. Our findings are therefore evidence of the usefulness of p16 as a diagnostic biomarker between HSIL and SCCC, as previously proposed [18,19]. In fact, it has facilitated inter-observer agreement and then has improved the accuracy of traditional diagnostic methods based on histological observation in lower grade lesions [4][5][6]21,30].…”

“…Although p16 overexpression is a potential biomarker for CC clinical management [5,17,18], there is a lack of consensus [5,19] and standard guidelines [2] concerning its routine use. Similarly, the biological significance of the paradoxical activation of this tumor-suppressor protein in CC is not yet well understood.…”

“…The cyclin-dependent kinase inhibitor 2A protein, also called p16, is a well-known tumor-suppressor protein which is down-regulated in many tumors, and is involved in regulating cell cycle, senescence, apoptosis, cell invasion and angiogenesis [3,5,15]. In spite of these well-recognized tumor-suppressor properties, p16 expression paradoxically increases with the severity of the cervical lesion [3,5,14,16], and has been then proposed as a useful marker for identifying such lesions [5,[17][18][19][20]. In fact, its ancillary use in cervical cytology has improved the accuracy of histological diagnosis [5,21], mainly in premalignant lesions [4].…”

“…As there is a lack of consensus and clear guidelines regarding the use of p16 expression in routine clinical management of SCCC [2,5,19], we aimed to shed some light on the clinical utility and biological significance of p16 overexpression during SCCC progression.…”