• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3281-3285
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• 2012

Objectives: To evaluate the clinicopathologic correlation and prognostic value of HPV18 DNA viral load in patients with early-stage cervical neuroendocrine carcinoma (NECA). Methods: Formalin-fixed, paraffin-embedded tissue of cervical NECA patients with known HPV18 infection and clinicopathologic data including follow-up results were collected. The HPV18 DNA load was assessed with quantitative PCR targeting the HPV18 E6E7 region. Results: Twenty-one patients with early-stage (IB-IIA) cervical NECA were identified. HPV18 DNA viral load ranged from 0.83 to 55,174 copies/cell (median 5.90). Disease progression, observed in 10 cases (48%), was not significantly associated with any clinicopathologic variables. However, the group of patients with progressive disease tended to have a higher rate of pelvic lymph node metastasis (50% versus 9%, p=0.063) and a lower median value of HPV18 DNA viral load (4.37 versus 8.17 copies/cell, p=0.198) compared to the non-recurrent group. When stratified by a cut-off viral load value of 5.00 copies/cell, the group of patients with viral load ${\leq}5.00$ copies/cell had a significantly shorter disease-free survival than the group with viral load >5.00 copies/cell (p=0.028). The group with a lower viral load also tended to have a higher rate of disease progression (75% versus 31%, p=0.080). No significant difference in the other clinicopathologic variables between the lower and higher viral load groups was identified. Conclusion: HPV18 DNA viral load may have a prognostic value in patients with early-stage NECA of the cervix. A low viral load may be predictive of shortened disease-free survival in these patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4297-4302
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• 2015

Background: To evaluate HPV testing by Hybrid Capture II (HCII) in conjunction with cytology in detecting the residual/recurrence disease after treatment of high-grade cervical intraepithelial neoplasia (CIN II-III) with loop electrosurgical excision procedure (LEEP). Materials and Methods: A retrospective review of 158 patients with histologically confirmed CIN II-III who underwent LEEP between January 2011 and October 2012 was conducted. Post-treatment control was scheduled at the 3rd, 6th, 12th and 18th month. All patients were followed up by Pap smear and HR-HPV genotype and viral load testing. Results: Pre-treatment, HR-HPV DNA, was detected in all specimens of the patients. At follow-up, 25 patients were diagnosed as the residual/recurrent disease during the FU visit, among whom, 16 patients with positive margin: 13 patients (52%) with HR-HPV DNA+/cytology+, 2 patients (8%) with HR-HPV DNA+/cytology-, 1 patient (4%) with cytology+/HR-HPV DNA-; 9 patients with clean margin - 5 patients (55.6%) with HR-HPV DNA+/cytology+; 2 patients (22.2%) with HRHPV DNA+/cytology-, 2 patients (22.2%) with cytology+/HR-HPV DNA-. None of them persisting HR-HPV DNA-/cytology-with positive or negative margin was identified as the residual/recurrent disease. The majority of residual/recurrent disease was detected at the 12th and 18th month FU, and there was almost no difference in the sensitivity and negative predictive value (NPV) between at the 3rd month and the 6th month FU visits. 14 residual/recurrence disease (14/46:30.4%) had pre-treatment high viral load (>5 000 RUL/PC) and 11 (11/112, 9.8%) with pre-treatment low viral load, P<0.05. Conclusions: (1) The persistence HR-HPV DNA is the root cause of the residual/recurrent disease for the women treated for high-grade CIN; the pre-treatment viral load and margin can be seen as the predictor. (2) The FU visit beginning at the 6th month post-treatment and lasting at least 24 months with the combination of cytology and HPV testing. (3) Patients with high pre-treatment HPV load, which is considered as one risk of developing the residual/recurrent disease, should be paid more attention (especially above 500RUL/PC) to by clinicians.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6379-6384
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• 2012

Objective: To investigate the relationship between plasma EBV-DNA concentration and clinicopathologic features of Hodgkin's lymphoma cases. Methods: At first, the positive rate of plasma EBV-DNA was determined with a nested-PCR method using 45 specimens from Uygur HL patients, as well as 110 healthy people sampled as normal controls. Secondly, using fluorescent quantitative nested-PCR, EBV viral load was assessed in the EBV-DNA positive plasma samples. Then, relationships between plasma EBV viral load and clinicopathologic features of HL patients were analyzed. Results: The positive rate of plasma EBV-DNA of HL patients was significantly higher than that of normal controls (53.3% vs 26.4%, P=0.001). There was no significant difference about plasma EBV viral load between EBV-associated HL and EBV-DNA positive normal people (P=0.490). Looking at patients' characteristics, plasma EBV viral load in 10-20 years EBV-associated HL was higher than in EBV cases which were less than 10 years or more than 35 years (P=0.025). Furthermore, in EBV-associated HL, concentration of plasma EBV-DNA was significantly higher in advanced stage disease (stages III-IV; P=0.013), and with B-symptoms (P=0.020). Conclusion: EBV-DNA levels were associated with part of clinicopathologic features of cases. It was of practical use to screen HL. Further etiological studies appear warranted.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4927-4935
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• 2015

Northeastern India is a major nasopharyngeal carcinoma (NPC) high risk-area although the rest of the country has very low incidence. A case-control study of 105 NPC cases and 115 controls was conducted to identify the potential risk factors for NPC development in this region. Information was collected by interviewer about socio-demographic characteristics, cigarette smoking, alcohol consumption, dietary history, occupational history, and a family history of cancer. Epstein-Barr viral load was assayed from the blood DNA by real time PCR. Associations between GSTs genotypes, cytochrome P450 family including CYP1A1, CYP2E1 and CYP2A6 polymorphisms and susceptibility to relationship between the diseases were studied using PCR-RFLP assay. Results indicate that Epstein-Barr virus load was significantly higher in patients compared to controls (p<0.0001). Furthermore, concentration of blood EBV-DNA was significantly higher in advanced stage disease (Stage III and IV) than in early stage disease (Stage I and II) (p<0.05). Presence of CYP2A6 variants that reduced the enzyme activity was significantly less frequent in cases than controls. Smoked meat consumption, exposure to smoke, living in poorly ventilated house and alcohol consumption were associated with NPC development among the population of Northeastern India. Thus, overall our study revealed that EBV viral load and genetic polymorphism of CYP2A6 along with living practices which include smoked meat consumption, exposure to smoke, living in poorly ventilated houses and alcohol consumption are the potential risk factors of NPC in north eastern region of India. Understanding of the risk factors and their role in the etiology of NPC are helpful forpreventive measures and screening.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2145-2150
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• 2015

HPV viruses are integral to the development of cervical cancer. The pathogenesis has been extensively studied. To date, numerous HPV tests and products have been developed and successfully utilized in diagnosis, treatment and prevention of cervical cancer. The HPV DNA test, when combined with other routine cervical cancer screening and diagnostic tests namely exfoliative cytology, visual inspection with acetic acid (VIA) and colposcopy has increased the detection rate of cervical cancer. HPV DNA products could also be measured in other body fluids like urine, lymph node tissue, and serum. HPV association could also be quantified by measuring other parameters like HPV mRNA, viral load, viral integration and methylation status. Vaccination against HPV has been found to decrease the incidence of cervical cancer. Further, therapeutic vaccines for cervical cancer against HPV continue to evolve. All these findings pertaining to HPV could possibly decrease the incidence of cervical cancer in the near future. This review aims to give an overview of the HPV tests and products in use and those under trial currently.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2643-2646
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• 2012

Objectives: Human papillomavirus (HPV) is the major etiological agent of cervical cancer, a leading cause of morbidity and mortality in women worldwide. Screening strategies for reducing the burden of HPV-mediated carcinogenesis are emerging as an effective means for cervical cancer control and prevention in developing countries. Our study, therefore, aimed to identify HPV infection status in North Indian women during random population screening. Methodology: Cervical/vaginal exfoliated cells and/or Pap smear specimens were collected from 890 women of North Indian ethnicity residing in Lucknow and adjoining areas, during random population screening from June 2009-March 2012. HPV viral loads in clinical specimens were determined by the Hybrid Capture (hc)-2 HPV DNA assay, and subsequently, positive/negative/borderline HPV status was calculated. Results: The HPV incidence in the present study was 11.7%. 751 out of a total of 890 women (84.4%) participating in our HPV screening program were HPV negative (HPV -), 104 (11.7%) tested positive (HPV +) while 35 (3.9%) showed borderline (HPV $^*$) infection status. Furthermore, in the HPV + subjects (N=104), 18 (17.3%) showed strong positivity. We observed that HPV positivity tends to increase with age in North Indian women; the higher the viral load with increasing age, higher is the susceptibility to HPV-mediated cervical cancer. Conclusions: HPV viral load/genotyping may help in identifying women at risk of developing cervical cancer. However, cost-effective HPV screening protocols with a wider population coverage are warranted so as to reduce the burden of cervical cancer in women worldwide in the vaccine-era.

• Journal of Life Science
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• v.27 no.3
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• pp.283-288
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• 2017

Porcine circovirus type 2 (PCV2) is a notorious and ubiquitous virus in the swine industry. The susceptibility of the host to PCV2 infection is considered to be one factor associated with the dynamics of PCV2. The objective of this study was to verify the criteria for host susceptibility to PCV2, using blood parameters of post-weaned pigs naturally infected with the virus. The PCV2 DNA viral load, antibody titer, and leukopenia characteristics were measured in the serum extracted from the pigs at the 10th week. We classified the pigs into high (>5.0), intermediate (3.0 to 5.0), and low (<3.0) groups on the basis of the PCV2 viral load (log copies/ml), or as positive (${\leq}0.50$) and negative (>0.50) groups on the basis of antibody titer (sample-to-negative corrected ratio). Moreover, using these two categorized parameters, we suggested the criteria for classification into the susceptible and resistant groups. Statistical analyses revealed that pigs in the susceptible group had a significantly higher viral load (p<0.001) and negative antibody titer (p<0.001), as well as significantly lower leukocyte counts (p=0.018) and lower amounts of several leukocyte components (p<0.05), than pigs in the resistant group. We concluded that the susceptible group could be considered to have PCV2-induced leukopenia. Therefore, we suggest that the combined classifications of viral loads and anti-PCV2 antibodies can be used to determine PCV2-induced leukopenia in the subclinical PCV2 infection of post-weaned pig populations.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6109-6113
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• 2012

Background: Oral cancer has become one of the most prevalent cancers worldwide and human Papillomavirus is one of the risk factors for developing oral cancer. For this study HPV18 was chosen as it is one of the high risk HPV types and may lead to carcinogenesis. However, prevalence of HPV18 infection in Oral Squamous Cell Carcinoma in Malaysia remains unclear. Objective: This study aimed to investigate the viral load of HPV18 DNA in OSCC and potentially malignant lesions using saliva samples. Materials and Methods: Genomic DNAs of thirty saliva samples of normal subjects and thirty saliva samples compromised of 16 samples from potentially malignant lesions and 14 of OSCC patients were amplified for HPV18 DNA using a nested polymerase chain reaction analysis. All PCR products were then analyzed using the Bioanalyzer to confirm presence of HPV18 DNA. Result: From thirty patients examined, only one of 30 (3.3%) cases was found to be positive for HPV18 in this study. Conclusion: The finding of this study revealed that there is a low viral detection of HPV18 in Malaysian OSCC by using saliva samples, suggesting that prevalence of HPV18 may not be important in this group of Malaysian OSCC.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.15 no.1
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• pp.38-43
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• 2012

Purpose: Epstein-Barr virus (EBV) hepatitis is a usually asymptomatic and self-limiting disease in immunocompetent patients. However, the range of severity is wide, and the serological diagnosis is typically difficult until the convalescent phase. Thus, we examined the value of plasma EBV DNA real-time quantitative polymerase chain reaction (RT-qPCR) in EBV hepatitis for the timely diagnosis and the relationship between EBV viral load and clinical severity. Methods: Sixty samples were confirmed as having EBV infection by RT-qPCR with the EBV BALF5 gene sequence. We examined the clinical characteristics of EBV hepatitis by reviewing medical records. Results: The median total duration of fever was 8 days (range: 0-13 days). The mean peak value of aspartate aminotransferase (AST) was $241{\pm}214$ U/L, and the mean peak value of alanine aminotransferase (ALT) was $298{\pm}312$ U/L. There was no correlation between the serum levels of liver enzyme and plasma EBV DNA titer ($p$=0.1) or between median total duration of fever and EBV DNA titer ($p$=0.056). The median age of the EBV VCA IgM-negative group was lower compared with the EBV VCA IgM-positive group in EBV hepatitis (2 years vs. 6 years, $p$=0.0009). Conclusion: The severity of EBV hepatitis does not correlate with circulating EBV DNA load according to our data. Furthermore, we suggest that plasma EBV PCR may be valuable in young infants in whom the results of serology test for EBV infection commonly are negative.

• The Korean Journal of Blood Transfusion
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• v.23 no.2
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• pp.152-161
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• 2012

Background: Since Jan. 2012, for performance evaluation of viral reagents, analysis of domestic samples has been recommended in order to obtain approval from the KFDA when they are first introduced to Korea. This regulation requires the standard domestic materials driven from locally infected samples. We tried manufacturing the plasma working standards of HBV, HCV, and HIV NAT using a mixed titer of viral loads. Methods: Forty three HBV DNA positive plasmas, 25 HCV RNA positive plasmas, and 26 HIV RNA positive plasmas were evaluated according to viral load and genotype. Several plasma units, which had high-titer viral loads and the common viral genotypes in Korea, were selected as the source materials for each viral standard. To adjust the appropriate concentration based on the detectable range of variable viral reagents, the source plasma was diluted to several concentrations, divided into small vials, and analyzed for quantification. Results: The 13 plasma working standards, which had variable viral loads for the mixed titer performance panel of HIV, HCV, and HBV NAT, were produced. Conclusion: These national standard materials were first produced in order to supply the mixed titer performance panel for the viral NAT reagent of the level IV transfusion related high-risk group in Korea.