p16 promoter methylation, expression, and its association with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 subtype of breast carcinoma

Objectives: The purpose of the study is to investigate p16 protein expression and promoter methylation of p16 gene and their association with molecular subtypes based on parameter such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Materials and Methods: A total of 114 breast cancer tissue biopsies were collected for methylation-specific polymerase chain reaction (MSP) and immunohistochemical (IHC) analysis. Results: Seven tissue microarrays were constructed. p16 protein expression was studied in 114 cases, of which 35/114 (30.7%) cases showed strong expression and the majority of them had ER-positive tumor (57.6%), and it was statistically significant (P < 0.0074). Similarly, p16 expression was reduced in the majority of PR-negative tumors (83.9%) and the association was statistically significant (P = 0.0026). p16 methylation was studied in 114 cases and was positive in 71.0% cases. Conclusion: High p16 protein expression was associated with ER-positive, PR-negative, and HER2-negative tumors which is associated with poor prognosis. p16 protein expression may be used as a prognostic indicator to predict treatment response to hormonal therapy.

Physical state & copy number of high risk human papillomavirus type 16 DNA in progression of cervical cancer.

Background & objectives: High-risk human papilloma virus (HR-HPV) infection and its integration in host genome is a key event in malignant transformation of cervical cells. HPV16 being a dominant HR-HPV type, we undertook this study to analyze if viral load and physical state of the virus correlated with each other in the absence of other confounding variables and examined their potential as predictors of progressive cervical lesions. Methods: Both, viral load and integration status of HPV16 were determined by real time URR PCR and estimation of E2:E6 ratio in a total of 130 PGMY-RLB -confirmed, monotypic HPV16-infected cervical DNA samples from biopsies of cytology-confirmed low grade (LSIL, 30) and high grade (HSIL, 30), and invasive carcinoma, (squamous cell carcinoma SCC, 70) cases. Results: Investigation of DNA samples revealed a gradual increase in HPV16 viral load over several magnitudes and increased frequency of integration from LSIL to HSIL and HSIL to invasive cancer in relation to the severity of lesions in monotypic HPV16-infected cervical tissues. In a substantial number of precancer (11/60) and cancer cases (29/70), HPV16 was detected in concomitant mixed form. The concomitant form of HPV16 genome carried significantly higher viral load. Interpretation & conclusions: Overall, viral load and integration increased with disease severity and could be useful biomarkers in disease progression, at least, in HPV16-infected cervical pre-cancer and cancer lesions.

Anti-human papillomavirus therapeutics: Facts & future.

Even after 25 years of establishing Human Papillomavirus (HPV) as the causative agent for cervical cancer, effective treatment of HPV infection still unavailable. Comprehensive efforts especially for targeting HPV infection have been made only in recent years. Conventional physical ablation of HPV-induced lesions such as cryo-therapy, photo-therapy, LEEP, laser cone-biopsy and localized radiotherapy are shown to be effective to some extent in treating localized lesions where the removal of diseased tissue is associated with removal of transforming keratinocytes harboring HPV. Apart from currently available prophylactic vaccines which prevent the viral entry and should be given prior to viral exposure, several attempts are being made to develop therapeutic vaccines that could treat prevailing HPV infection. In addition, immunomodulators like interferons and imiquimod that have been shown to elicit cytokine milieu to enhance host immune response against HPV infection. Also, antiviral approaches such as RNA interference (RNAi) nucleotide analogs, antioxidants and herbal derivatives have shown effective therapeutic potential against HPV infection. These leads are being tested in pre-clinical and clinical studies. Present article provides a brief overview of conventional therapies for HPV-associated diseases. Potential of non-ablative anti-HPV treatment modalities that could prove useful for either elimination of HPV in early stages of infection when the virus is not integrated into the host cell genome or suppression of the expression of viral oncogenes that dysregulate the host cell cycle following transformation is discussed.

Infection of human papillomaviruses in cancers of different human organ sites.

Clinico-epidemiological and molecular studies have established the casual link between Human Papillomavirus (HPV) infection and cervical cancer as also association of HPV infection with several other cancers. In India, cervical cancer is a leading cancer among women and almost all cases of cervical cancer show prevalence of High Risk (HR)-HPV infection. HPV has been also detected in a significant proportion of oral, esophageal, anal, vaginal, vulvar, and penile cancer and in a small percentage of lung, laryngeal, and stomach cancer in India. Due to lack of organized HPV screening program, insufficient infrastructure and trained manpower and inadequacy in cancer registries, there are not much data available on the countrywide HPV prevalence and its type distribution in different cancers in India. Forthcoming introduction of recently developed HPV vaccines in India given a new urgency to know the prevalence and distribution of various HPV types in different organ sites for the management and monitoring of vaccination program and its impact on prevalence of other cancers. This review, summarizes studies on the prevalence of HPV infection in cancers of different organ sites in India.

Adrenocorticotropic hormone production in breast cancer.

Presence of adrenocorticotropic hormone (ACTH) was investigated in tissues from 150 cases of primary breast cancer. ACTH peptides were detected in 16.7% cases and ACTH expression was higher in post-menopausal cancers. A significant association was noticed between the presence of ACTH and the positive estrogen receptor (ER) status of tumors. The study indicated a probable role of these ectopic ACTH peptides in steroid hormone related pathology of breast cancer.