Abstract
Objective: We aimed to retrospectively examine a series of premalignant and malignant cervical tissues to study a high-risk HPV 16 infection that, among cervical tissue lesions, carries the greatest risk of conversion to cancer, and the presence of p53 protein immunoreactivity, a tumor suppressor gene product. Methods: Paraffin blocks were studied via immunohistochemical (IHC) method to explore the presence of HPV 16 in 59 premalignant and malignant cervical lesions as well as immunoreactivity of the p53 oncoprotein, the most common cellular tumor suppressor gene product in human cancers. Results: In our series, mutant p53 positivity rate was 35.3% for low-grade CIL, 40% for high-grade CIL, and 46.8% for invasive carcinoma cases. Immune staining for high-risk HPV 16 type yielded a positive staining rate of 47% in low-grade CIL, 80% in high-grade CIL, and 50% in invasive carcinoma. Conclusion: The results of our study indicate a progressive increase in p53 oncoprotein reactivity from cervical intraepithelial neoplasia to invasive carcinoma. This suggests the clinical importance of p53 immunoreactivity in dysplastic progression and neoplastic transformation. HPV is the most commonly encountered oncogenic type in cervical lesions, especially in high-grade CIL and invasive carcinomas. Results of the previous reports suggest that HPV-positive carcinomas release wild type p53 and HPV-negative ones release mutant type p53 were not confirmed by our results, which indicated a mutant type p53 reactivity in HPV- 16 positive carcinoma cases.
Highlights
Cervix carcinoma is the third most common cancers in women worldwide and most of cases occurring in lowto-medium-resource countries
Infections by oncogenic high risk (HR) HPV are the most important factor in its etiology; it has been demonstrated that E6 and E7 oncoproteins of HPVs are bound to tumor suppressor genes p53 and Rb and eliminate their tumor suppressing properties, inducing malignancies
When high-level p53 accumulation is taken into consideration, there was a significant difference between invasive cancers and high-grade and low-grade intraepithelial lesions with respect to staining (x2 = 6.44, p = 0.009 and x2 = 7.98, p = 0.012, respectively)
Summary
Cervix carcinoma is the third most common cancers in women worldwide and most of cases occurring in lowto-medium-resource countries. The introduction of screening programs in many high resource countries has successfully decreased cervical cancer incidence and mortality. At least 13 genotypes of the alpha genus (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) have been found to be associated with the risk to develop cervical cancer and defined as “carcinogenic” viral types [1]-[5]. HPV typing has been shown to be a criterion determining which cervical intraepithelial neoplasia (CIN) lesions will turn into cancer. HPV16 is the most prevalent genotype in both squamous cell carcinoma (59.3%) and adenocarcinoma (36.3%) across the world. There is a strong correlation between HPV 16 and CIN2-3 lesions
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