Amir Sohrabi

The point mutation analysis of Cyp2C9*2 (Arg144Cys C>T), Cyp2C9*3 (Ile359Leu A>C) and VKORC1 (1639G>A) in women with cervical cancer related to HPV: A case‐control study

AbstractHuman papillomavirus (HPV) is the most common sexually transmitted viral infection worldwide. HPV tumorigenesis genotypes are the causative agents of cervical cancer and genital malignancies. The scientific literature has demonstrated that life style, environmental, epigenetic accompanied with HR‐HPV genotypes are potential risk factors for cervical cancer progression. The frequencies of the Cyp2C9*2, Cyp2C9*3, and vitamin K epoxide reductase complex subunit 1 (VKORC1) genotypes as potential molecular biomarkers have been investigated on Iranian women with cervical malignancy related to HPV genotypes. As a case‐control study, the mutations were appraised using a polymerase chain reaction‐restriction fragment length polymorphism procedure on women suffering from HPV infection (60 cases), CC (46 cases), and 40 subjects of as healthy control. The outcomes demonstrated that Cyp2C9*3 showed a meaningful relationship between women diagnosed with cervical cancer and the healthy population (AA vs. AC; OR, 7.15; 95% CI, 1.94‐26.3; p = .003). It was also observed that the Cyp2C9*3 mutation in women with cervical cancer and VKORC1 in healthy population with HPV (+), did not follow the Hardy–Weinberg equilibrium. Our findings aid understanding the genetic polymorphism distribution of Cyp2C9*2, Cyp2C9*3, and VKORC1 in women with genital malignancies. This can also be useful in predicting the susceptibility risk factors for developing cervical cancer. However, allelic discrimination as a molecular biomarker requires further research.

miR-21 and miR29-a: Potential Molecular Biomarkers for HPV Genotypes and Cervical Cancer Detection

Background and objective: This study aimed to assess miR21 and miR-29a diagnostic usefulness for HPV infection and Cervical Cancer (CC) detection. Methods: miRs extraction has been performed on HPV-positive, CC and negative control of 43, 50 and 46 individuals, respectively. The expression level of miRs has been analyzed using Real-Time RT-PCR. Results: There was a correlation between the expression of miRs and the Receiver Operating Characteristic (ROC) analysis in CC and HPV-positive patients. Conclusion: The correlation between expressions of miRs is notable. ROC curve analysis could be applied in molecular diagnostic exposure for CC related to HPV infections.

Lead (Pb) exposure from outdoor air pollution: a potential risk factor for cervical intraepithelial neoplasia related to HPV genotypes

Abstract Human papillomavirus genotypes (HPVs) have been confirmed to be the major cause of cervical intraepithelial neoplasia (CIN) that remains to be one of the most common women cancers around the world. It seems other risk factors have synergistic effects on cervical cancer occurrence including smoking, dietary pattern, sexual behavior, ethnicity, epigenetics, and environmental hazardous materials. Our study characterized the potential cancerous role of lead (Pb) as a common toxic environmental pollutant agent on CIN outcomes. Lead concentration was quantified using an atomic absorption spectrometer in liquid-based cytology specimens of 40 CIN-HPV positive subjects, 50 HPV infected non-cancerous cases, and 43 non-HPV infected/non-cancerous women. Pb concentration was 5.5 (4.7–6.4) μg/dL, 4.7 (4.2–8.7) μg/dL, and 4.7 (4.5–5.4) μg/dL in the CIN-HPV positive group, HPV infected non-cancerous cases, and non-HPV infected/non-cancerous group, respectively. The results showed higher Pb concentration is associated with higher risk for cervical malignancy in comparison with non-HPV infected/non-cancerous subjects, after controlling for age effect (aOR = 4.55, 95% CI: 1.55–15.07, P < 0.01). Our finding suggested a direct significant association between Pb accumulation and CIN existence. The consequences need to be further validated by including more relevant risk factors and controlling the confounders for better understating of Pb impact from outdoor air pollution on cervical cancer progression.

Trends in cocirculation of oncogenic HPV genotypes in single and multiple infections among the unvaccinated community

AbstractCocirculation of multiple human papillomavirus (HPV) infections with low, probably high, and high‐risk genotypes are to be associated with various grades of infections and cancer progression. The oncogenic high‐risk HPVs are distributed and cocirculated throughout the world. This study was investigated to identify HPV genotypes related to genital disorders in unvaccinated women. The subjects were referred from clinics to a molecular lab for HPV testing in Iran as a low‐coverage vaccinated country. HPVs DNAs of cervical scrapping and genital tissue specimens of 1,133 un‐vaccinated women were genotyped using an in vitro diagnostic line probe (reverse hybridization) assay. In addition, phylogenetic trees were constructed on 100 MY09/MY11 polymerase chain reaction (PCR) amplicons of common genotypes of HPV L1 gene by Sanger sequencing. The mean age of the population study was 32.7 ± 8.0 and the mean age of HPV‐positive cases was 31.6 ± 7.8. HPV DNA was detected in 57.8% (655/1133) of women subjects and 42.2% (478/1133) of cases were undetected. Among 655 HPV‐positive cases, 639 subjects (56.4%) were related to defined genotypes and 16 subjects (1.4%) were untypeable. The highest prevalence rate of HPV genotypes was identified in the 25–34 years. The top 6 dominant HPVs in single and multiple genotypes were HPV6 (284/655 [43.4%]), HPV16 (111/655 [16.9%]), HPV31 (72/655 [11%]), HPV53 (67/655 [10.2%]), HPV11 (62/655 [9.5%]), and HPV52 (62/655 [9.5%]). Moreover, single, multiple and untypeable HPV genotypes were diagnosed as follows: 1 type (318/655 [48.5%]), 2 types (162/655 [24.8%]), 3 types (83/655 [12.7%]), 4 types (42/655 [6.5%]), more than 5 types (34/655 [5.3%]), and 1.4% un‐typeable subjects. The sequenced partial L1 gene of HPV genotypes (GenBank databases under the accession numbers: MH253467‐MH253566) confirmed and determined the cocirculated HPV genotypes' origins and addressed helpful insights into the future viral epidemiology investigations. Multiple HPV infections and cocirculation of various oncogenic HPV genotypes among the normal population (women and men) with asymptomatic forms are still challenging in unvaccinated communities. The preventive and organized surveillance programs for HPV screening are needed to be considered and compiled by health policy makers of low or unvaccinated countries.