HPV16-E6/E7 Oncogene Mutation and p53 Expression among Indonesian Women with Cervical Cancer.

OBJECTIVE: To characterize HPV16 E6/E7 mutation and its association with p53 expression among Indonesian women with cervical cancer. METHODS: This is a cross-sectional study involving 31 Indonesian women with pathologically proven cervical cancer and HPV16 infection. Data about the clinical characteristics of the study population were obtained from the medical records. Biopsy specimen of the cervical cancer mass from each study participant was obtained for DNA isolation. The ORFs of E6 and E7 genes were amplified using specific primer designed according to K02718/HPV16R gene sequence obtained from GenBank. Sequencing was performed using software program MEGA10. HPV16 E6 and E7 prototype sequences for nucleotide alignment (HPv16. P, GenBank Access code: NC_001526) was selected from European variant. The sequence of nucleotide and amino acid was aligned using software program BioEdit. p53 expression was evaluated through immunohistochemistry and quantified using immunoreactivity score (IRS). RESULTS: Twelve subjects (38.7%) present with E6 and E7 mutation. Median age, parity, stage and histologic type of the tumour did not associate with E6/E7 mutation. E6 and E7 mutation rate was 25.8% (8/31) and 12.9% (4/31), respectively. Seven single nucleotide changes were identified within the E6 and E7 oncogenes, including four non-synonymous and three synonymous mutations. E6 T27C was the most prevalent mutation (16.1%). Nonsynonymous mutations were more prevalent within E7 gene (9.6%) (N29T, N29S, and R77C). Median IRS did not differ between HPV16-E6/E7 variants and wildtype (p value = 0.990). There was no association between E6/E7 mutations and p53 expression in Indonesian women with cervical cancer (PR 1.4, 95% CI: 0.29-6.77, p value = 0.704). CONCLUSIONS: HPV16 E6 mutation was more prevalent than E7 mutation among Indonesian women. There was no association between E6/E7 mutation and p53 expression level.

Diagnostic accuracy of serum insulin-like growth factor-binding protein 2 for ovarian cancer.

INTRODUCTION: Insulin-like growth factor-binding protein 2 (IGFBP2) plays an important role in the pathogenesis of ovarian cancer. The most prominent effects of IGFBP2 include promoting proliferation, driving invasion, and suppressing apoptosis. This study aimed to determine the diagnostic accuracy of serum IGFBP2 in differentiating between benign and malignant ovarian neoplasms. METHODS: Preoperative serum IGFBP2 level was evaluated from 76 women with primary ovarian tumor who underwent exploratory laparotomy at Sanglah General Hospital, Denpasar, Bali, Indonesia. The optimal threshold value of IGFBP2 for the diagnosis of ovarian cancer was determined from the receiver 0perating characteristic (ROC) curve. The diagnosis was confirmed by histopathologic analysis of resected ovarian specimens. RESULTS: Forty-six (60.5%) patients were diagnosed with ovarian cancer. The area under the ROC curve (AUC) of IGFBP2 in detecting ovarian cancer was 0.815 (95% CI: 0.721 to 0.910, P<0.001). For a given specificity larger than 95%, the optimal sensitivity was 63%. The optimal threshold value of IGFBP2 for the diagnosis of ovarian cancer was 804 ng/mL [sensitivity 63%, specificity 96.7%, positive predictive value (PPV) 96.7%, negative predictive value (NPV) 63%, accuracy 76.3%, and diagnostic odd ratio (DOR) 49.5 (95% CI 6.1 to 396.5)]. In a subgroup analysis, IGFBP2 showed excellence performance in diagnosing advanced ovarian cancer (AUC 0.904 [95% CI: 0.806 to 1.000], sensitivity 83.3%, specificity 96.7%, PPV 95.2%, NPV 87.9%, accuracy 90.7%, and DOR 145.0 [95% CI 15.0 to 1395.3]). CONCLUSION: IGFBP2 is a novel and potentially promising biomarker for detecting ovarian cancer. Further studies are needed to confirm its diagnostic performance in premenopausal women and for detecting early stage ovarian cancer.

Impact of human papilloma virus vaccination on adolescent knowledge, perception of sexual risk and need for safer sexual behaviors in Bali, Indonesia.

AIM: To determine the impact of human papilloma virus (HPV) vaccination on knowledge, perception of sexual risk and need for continued safe sexual behavior among Indonesian girls. METHODS: A comparative cross-sectional study was carried on in Denpasar, the capital city of Bali, Indonesia, during September 2015-February 2016. A total of 828 adolescent girls (12-16 years) were recruited to assess their knowledge on HPV/HPV vaccine, perception of sexual risks and need for continued safe sexual behavior. RESULTS: A total of 419 girls (50.7%) had received HPV vaccination prior to the study, 76.4% of whom (320/419) had sufficient knowledge about HPV. HPV vaccination was a strong and independent predictor of higher HPV/HPV vaccine knowledge (adjusted OR [AOR], 9.358; 95%CI: 6.816-12.849, P < 0.001). HPV vaccination (AOR, 0.107; 95%CI: 0.074-0.155, P < 0.001) and higher knowledge level (AOR, 0.667; 95%CI: 0.464-0.958, P = 0.028) were associated with lower perceived HPV risk. Despite the low risk perception, most of the vaccinated girls (408/419, 97.4%) continued to perceive higher need for safe sexual behaviors. On multivariate analysis, higher knowledge was the independent predictor for higher perceived need for safe sexual behaviors (AOR, 4.260; 95%CI: 2.016-9.001, P < 0.001). CONCLUSION: The HPV vaccination was associated with higher knowledge and appropriately lower perception of HPV risk. Despite the vaccination, most of the adolescents continued to perceive a need for safer sexual behavior. All adolescent girls should receive HPV vaccination in order to reduce cervical cancer burden in the future.

The prospect of induced pluripotent stem cells for diabetes mellitus treatment.

A continuous search for a permanent cure for diabetes mellitus is underway with several remarkable discoveries over the past few decades. One of these is the potential of pancreatic stem/progenitor cells to rejuvenate functional ß cells. However, the existence of these cell populations is still obscure and a lack of phenotype characterization hampers their use in clinical settings. Cellular reprogramming through induced pluripotent stem (iPS) cell technology can become an alternative strategy to generate insulin-producing cells in a relatively safe (autologous-derived cells, thus devoid of rejection risk) and efficient way (high cellular proliferation) but retain a precise morphological and genetic composition, similar to that of the native ß cells. iPS cell technology is a technique of transducing any cell types with key transcription factors to yield embryonic-like stem cells with high clonogenicity and is able to give rise into all cell lineages from three germ layers (endoderm, ectoderm, and mesoderm). This approach can generate ß-like pancreatic cells that are fully functional as proven by either in vitro or in vivo studies. This novel proof-of-concept stem cell technology brings new expectations on applying stem cell therapy for diabetes mellitus in clinical settings.