Displaying publications 21 - 34 of 34 in total

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  1. Ramesh T, Foo KL, R H, Sam AJ, Solayappan M
    Sci Rep, 2019 11 19;9(1):17039.
    PMID: 31745139 DOI: 10.1038/s41598-019-53476-9
    Detection of host integrated viral oncogenes are critical for early and point-of-care molecular diagnostics of virus-induced carcinoma. However, available diagnostic approaches are incapable of combining both cost-efficient medical diagnosis and high analytical performances. To circumvent this, we have developed an improved IDE-based nanobiosensor for biorecognition of HPV-16 infected cervical cancer cells through electrochemical impedance spectroscopy. The system is fabricated by coating gold (Au) doped zinc oxide (ZnO) nanorods interfaced with HPV-16 viral DNA bioreceptors on top of the Interdigitated Electrode (IDE) chips surface. Due to the concurrently improved sensitivity and biocompatibility of the designed nanohybrid film, Au decorated ZnO-Nanorod biosensors demonstrate exceptional detection of HPV-16 E6 oncogene, the cancer biomarker for HPV infected cervical cancers. This sensor displayed high levels of sensitivity by detecting as low as 1fM of viral E6 gene target. The sensor also exhibited a stable functional life span of more than 5 weeks, good reproducibility and high discriminatory properties against HPV-16. Sensor current responses are obtained from cultured cervical cancer cells which are close to clinical cancer samples. Hence, the developed sensor is an adaptable tool with high potential for clinical diagnosis especially useful for economically challenged countries/regions.
    Matched MeSH terms: Human papillomavirus 16/genetics*
  2. Nor Rashid N, Yusof R, Watson RJ
    J Gen Virol, 2011 Nov;92(Pt 11):2620-2627.
    PMID: 21813705 DOI: 10.1099/vir.0.035352-0
    Human papillomaviruses (HPVs) with tropism for mucosal epithelia are the major aetiological factors in cervical cancer. Most cancers are associated with so-called high-risk HPV types, in particular HPV16, and constitutive expression of the HPV16 E6 and E7 oncoproteins is critical for malignant transformation in infected keratinocytes. E6 and E7 bind to and inactivate the cellular tumour suppressors p53 and Rb, respectively, thus delaying differentiation and inducing proliferation in suprabasal keratinocytes to enable HPV replication. One member of the Rb family, p130, appears to be a particularly important target for E7 in promoting S-phase entry. Recent evidence indicates that p130 regulates cell-cycle progression as part of a large protein complex termed DREAM. The composition of DREAM is cell cycle-regulated, associating with E2F4 and p130 in G0/G1 and with the B-myb transcription factor in S/G2. In this study, we addressed whether p130-DREAM is disrupted in HPV16-transformed cervical cancer cells and whether this is a critical function for E6/E7. We found that p130-DREAM was greatly diminished in HPV16-transformed cervical carcinoma cells (CaSki and SiHa) compared with control cell lines; however, when E6/E7 expression was targeted by specific small hairpin RNAs, p130-DREAM was reformed and the cell cycle was arrested. We further demonstrated that the profound G1 arrest in E7-depleted CaSki cells was dependent on p130-DREAM reformation by also targeting the expression of the DREAM component Lin-54 and p130. The results show that continued HPV16 E6/E7 expression is necessary in cervical cancer cells to prevent cell-cycle arrest by a repressive p130-DREAM complex.
    Matched MeSH terms: Human papillomavirus 16/pathogenicity*
  3. Tan SC, Ismail MP, Duski DR, Othman NH, Bhavaraju VM, Ankathil R
    Cancer Invest, 2017 Mar 16;35(3):163-173.
    PMID: 28301252 DOI: 10.1080/07357907.2017.1278767
    This study aimed to identify the most stably expressed reference genes from a panel of 32 candidate genes for normalization of reverse transcription-quantitative real-time polymerase chain reaction data in cancerous and non-cancerous tissues of human uterine cervix. Overall, PUM1, YWHAZ, and RPLP0 were identified as the most stably expressed genes in paired cancerous and non-cancerous tissues. The results were further stratified by the state of malignancy of the tissues, histopathological type of the cancer, and the human papillomavirus-type.
    Matched MeSH terms: Human papillomavirus 16/physiology*
  4. Lang Kuhs KA, Anantharaman D, Waterboer T, Johansson M, Brennan P, Michel A, et al.
    Cancer Epidemiol Biomarkers Prev, 2015 Apr;24(4):683-9.
    PMID: 25623733 DOI: 10.1158/1055-9965.EPI-14-1217
    BACKGROUND: The increasing incidence of oropharyngeal cancer in many developed countries has been attributed to human papillomavirus type 16 (HPV16) infections. Recently, HPV16 E6 serology has been identified as a promising early marker for oropharyngeal cancer. Therefore, characterization of HPV16 E6 seropositivity among individuals without cancer is warranted.

    METHODS: A total of 4,666 controls were pooled from several studies of cancer and HPV seropositivity, all tested within the same laboratory. HPV16 E6 seropositive controls were classified as having (i) moderate [mean fluorescent intensity (MFI) ≥ 484 and <1,000] or (ii) high seroreactivity (MFI ≥ 1,000). Associations of moderate and high HPV16 E6 seroreactivity with (i) demographic risk factors; and seropositivity for (ii) other HPV16 proteins (E1, E2, E4, E7, and L1), and (iii) E6 proteins from non-HPV16 types (HPV6, 11, 18, 31, 33, 45, and 52) were evaluated.

    RESULTS: Thirty-two (0.7%) HPV16 E6 seropositive controls were identified; 17 (0.4%) with moderate and 15 (0.3%) with high seroreactivity. High HPV16 E6 seroreactivity was associated with former smoking [odds ratio (OR), 5.5; 95% confidence interval (CI), 1.2-51.8], and seropositivity against HPV16 L1 (OR, 4.8; 95% CI, 1.3-15.4); E2 (OR, 7.7; 95% CI, 1.4-29.1); multiple HPV16 proteins (OR, 25.3; 95% CI, 2.6-119.6 for three HPV16 proteins beside E6) and HPV33 E6 (OR, 17.7; 95% CI, 1.9-81.8). No associations were observed with moderate HPV16 E6 seroreactivity.

    CONCLUSIONS: High HPV16 E6 seroreactivity is rare among individuals without diagnosed cancer and was not explained by demographic factors.

    IMPACT: Some HPV16 E6 seropositive individuals without diagnosed HPV-driven cancer, especially those with seropositivity against other HPV16 proteins, may harbor a biologically relevant HPV16 infection.

    Matched MeSH terms: Human papillomavirus 16/immunology
  5. Lim BK, Ng KY, Omar J, Omar SZ, Gunapalaiah B, Teoh YL, et al.
    Med J Malaysia, 2014 Feb;69(1):2-8.
    PMID: 24814620
    INTRODUCTION: Cervical cancer is the third most common cancer in women worldwide. The HPV-16/18 AS04- adjuvanted vaccine (Cervarix©) has previously been shown to be highly immunogenic with a clinically acceptable safety profile. This phase IIIb, double-blind, randomized (1:1) and placebo controlled trial (NCT00345878) was designed to evaluate the vaccine immunogenicity against HPV-16 and HPV-18 as well as its safety and reactogenicity in Malaysian women.

    METHODS: Healthy women aged 18-35 years received intramuscularly three doses of either the vaccine (HPV group) or aluminium hydroxide (ALU group) at 0, 1, and 6 months. Antibody titers were measured by an enzyme-linked immunosorbent assay (ELISA).

    RESULTS: A total of 271 eligible subjects were enrolled and 266 subjects completed the study. Initially seronegative subjects in the HPV group showed 100% seroconversion one month post-dose-3 for anti HPV-16 and anti-HPV-18 antibodies with geometric mean titers of 11107.5 (95% CI: 9727.3-12683.4) EL.U/mL and 4273.5 (95% CI: 3771.8-4841.9) EL.U/mL, respectively. Over 96% of subjects in both groups received all three vaccine doses. Solicited local (pain) and general symptoms (myalgia, fatigue, arthralgia and headache) were commonly reported in both HPV and ALU groups. Eight serious adverse events were reported throughout the study (five in the HPV group; three in the ALU group), all considered by investigators to be unrelated to vaccination.

    CONCLUSION: The HPV-16/18 AS04-adjuvanted vaccine was immunogenic and generally well tolerated in Malaysian women aged 18-35 years.
    Matched MeSH terms: Human papillomavirus 16
  6. Win Win Than, Tin Sabai Aung
    MyJurnal
    Introduction: Cervical cancer remains the second commonest female malignancy worldwide and the seventh among Malaysians. Globally in 2012, an estimated 528 000 women developed cervical cancer and almost 266 000 died from this disease. Of all cervical cancers, 83% occur in the less developed world due to the absence of screening. To promote the community health awareness of cervical cancer which is preventable. Methods: By internet literature searching (Google Scholar) and textbooks. Results: The primary cause of cervical pre-cancer and cancer is persistent infection with one or more of the oncogenic types of HPV, the most common infection acquired during sexual inter-course, usually early in sexual life. Cervical cancer due to HPV can be prevented by HPV vaccination, participation in a screening program, avoidance of smoking, limitation of sex partners and use of a condom. Three HPV vaccines are available worldwide such as bivalent HPV 16/18 vaccine, quadrivalent HPV 16/18/6/11 L1 virus-like particles vaccine and 9-valent HPV 6/11/16/18/31/33/45/52/58 recombinant vaccine. The HPV test can be done on the same sample of cells collected from the Pap test and it can help to know HPV types. Conclusion: Cervical cancer due to HPV can be prevented by vaccination and the pre-cancerous phase of cervical cancer can be screened by the HPV testing with the Pap test. The community health awareness plays a major role in cervical cancer prevention.
    Matched MeSH terms: Human papillomavirus 16
  7. Sharifa Ezat, W.P., Sharifah, N.A., Sayyidi Hamzi, A.R., Norin Rahayu, S., Shamsul Azhar, S., Syed Mohamed, A.
    Medicine & Health, 2010;5(2):66-76.
    MyJurnal
    A cross sectional study was done to determine the prevalence and distribution of human papillomavirus (HPV) genotypes in pre-invasive (cervical intraepithelial neoplasia, grade 3 or CIN 3) and invasive cervical cancer (ICC), in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). A total of 80 paraffin-embedded tumour tissue blocks (20 CIN 3, 60 invasive cancers) between 1999 to 2007 were retrieved from the archives of the Department of Pathology. Patient’s medical records were obtained from the Medical Records Office. Among invasive cancers (n=60), squamous cell carcinoma (SCC) account for 75% and adenocarcinoma 25%. The mean age of cases studied was 52.0 ± 12.2 years and Chinese was the predominant ethnicity (66.3%). Twelve HPV genotypes were identified, namely, HPV 16, 33, 18, 39,52, 45, 58, 59, 31, 35, 6 and 11. The prevalence of HPV was 92.5% with types 16 being the most common (73.8%), followed by types 33 (30%) and 18 (22.5%). A total of 31 cases (38.8%) showed single HPV genotype, while 43 (53.8%) had multiple HPV (two genotypes or more) genotypes. In ICC, HPV 16, followed by types 33, 18, 52 and 39 were the top five common HPV genotypes detected. High prevalence of HPV and multiple HPV infections were major findings among patients with pre-invasive and invasive cervical cancer.
    Matched MeSH terms: Human papillomavirus 16
  8. Khoo SP, Bhoo-Pathy N, Yap SH, Anwar Shafii MK, Hairizan Nasir N, Belinson J, et al.
    Sex Transm Infect, 2018 06;94(4):277-283.
    PMID: 29180538 DOI: 10.1136/sextrans-2017-053320
    OBJECTIVES: Cervical cancer is a largely preventable disease, and the strategic implementation of a cervical cancer prevention programme is partly dependent on the impact of human papillomavirus (HPV) infection interpreted within the context of the country's sociodemographic attributes. The objective of this study is to determine the prevalence of cervicovaginal HPV infection among a healthy, community-based, multiethnic Malaysian population. The HPV prevalence was subsequently correlated to the individual's sociodemographics and sexual/reproductive history. Of significance, the observed prevalence captured was in a birth cohort not included in the national school-based HPV vaccination programme.

    METHODS: This was a cross-sectional study where 1293 healthy women aged between 18 and 60 years were recruited via convenience sampling from five community-based clinics in Selangor, Malaysia. Cervicovaginal self-samples were obtained and DNA was extracted for HPV detection and genotyping. A comprehensive questionnaire was administered to determine the sociodemographics and behavioural patterns of participants.

    RESULTS: The median age at enrolment was 37 years old (IQR: 30-47). In total, 86/1190 (7.2%) of the samples collected were positive for HPV infection, with the highest HPV prevalence (11.9%) detected in the subgroup of 18-24 years old. The top three most prevalent HPV genotypes were HPV 16, 52 and 58. The independent risk factors associated with higher rates of HPV infection included Indian ethnicity, widowed status and women with partners who are away from home for long periods and/or has another sexual partner.

    CONCLUSIONS: The overall prevalence of HPV infection in this Malaysian multiethnic population was 7.2%, with 6.5% being high-risk genotypes. The top three most common high-risk HPV types were HPV 16, 52 and 58. This information is important for the planning of primary (HPV vaccination) and secondary (screening) cervical cancer prevention programmes in Malaysia.

    Matched MeSH terms: Human papillomavirus 16
  9. Velentzis LS, Hawkes D, Caruana M, Brotherton JM, Smith MA, Roeske L, et al.
    Tumour Virus Res, 2023 Jun;15:200255.
    PMID: 36736490 DOI: 10.1016/j.tvr.2023.200255
    Australia's cervical screening program transitioned from cytology to HPV-testing with genotyping for HPV16/18 in Dec'2017. We investigated whether program data could be used to monitor HPV vaccination program impact (commenced in 2007) on HPV16/18 prevalence and compared estimates with pre-vaccination benchmark prevalence. Pre-vaccination samples (2005-2008) (n = 1933; WHINURS), from 25 to 64-year-old women had been previously analysed with Linear Array (LA). Post-vaccination samples (2013-2014) (n = 2989; Compass pilot), from 25 to 64-year-old women, were analysed by cobas 4800 (cobas), and by LA for historical comparability. Age standardised pre-vaccination HPV16/18 prevalence was 4.85% (95%CI:3.81-5.89) by LA; post-vaccination estimates were 1.67% (95%CI:1.21-2.13%) by LA, 1.49% (95%CI:1.05-1.93%) by cobas, and 1.63% (95%CI:1.17-2.08%) for cobas and LA testing of non-16/18 cobas positives (cobas/LA). Age-standardised pre-vaccination oncogenic HPV prevalence was 15.70% (95%CI:13.79-17.60%) by LA; post-vaccination estimates were 9.06% (95%CI:8.02-10.09%) by LA, 8.47% (95%CI:7.47-9.47%) by cobas and cobas/LA. Standardised rate ratios between post-vs. pre-vaccination rates were significantly different for HPV16/18, non-16/18 HPV and oncogenic HPV: 0.34 (95%CI:0.23-0.50), 0.68 (95%CI:0.55-0.84) and 0.58 (95%CI:0.48-0.69), respectively. Additional strategies (LA for all cobas positives; combined cobas and LA results on all samples) had similar results. If a single method is applied consistently, it will provide important data on relative changes in HPV prevalence following vaccination.
    Matched MeSH terms: Human papillomavirus 16
  10. Van Ta T, Nguyen QN, Truong VL, Tran TT, Nguyen HP, Vuong LD
    Malays J Med Sci, 2019 Sep;26(5):151-157.
    PMID: 31728128 DOI: 10.21315/mjms2019.26.5.15
    Neuroendocrine cervical cancer is a rare subtype of cervical cancer with a highly aggressive malignancy. This study was conducted to analyse the human papillomavirus (HPV) infection and molecular abnormalities in Vietnamese neuroendocrine carcinomas of the uterine cervix. HPV genotyping and p53 mutations were examined using polymerase chain reaction (PCR)-based direct sequencing. Mutations of epidermal growth factor receptor (EGFR), Kirsten rat sarcoma (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B (BRAF) were identified using commercial kits. Four high-risk HPV genotypes were identified in 26 (86.7%) out of a total of 30 tumours. The prevalence of HPV 16, 18, 31 and 45 was 20.0%, 50.0%, 20.0% and 36.7%, respectively. Overexpression of p16INK4a was observed in 93.3% of cases and was significantly correlated with high-risk HPV infections. Furthermore, p53 and NRAS mutations were detected in five (16.7%) and one (3.3%) cases, respectively, whereas no EGFR, KRAS or BRAF mutations were observed. These results demonstrate that high-risk HPV infection may be an important oncogenic factor for the development and progression of cervical neuroendocrine carcinoma.
    Matched MeSH terms: Human papillomavirus 16
  11. Krishnappa P, Mohamad IB, Lin YJ, Barua A
    Diagn Pathol, 2014;9:202.
    PMID: 25361681 DOI: 10.1186/s13000-014-0202-z
    Cervical cancer is one of the most common cancers affecting women worldwide. It is well established that human papilloma virus (HPV) infection is the prime risk factor in the development of cervical cancer. The current screening and diagnostic tests have limitations in identifying the range of lesions caused by HPV. The current study aims to evaluate the diagnostic value of p16 immunohistochemical (IHC) investigation in high-risk human papillomavirus (HR-HPV) related lesions of the uterine cervix in Hospital Tuanku Jaafar, Seremban, Malaysia.
    Matched MeSH terms: Human papillomavirus 16*
  12. Van Kriekinge G, Sohn WY, Aljunid SM, Soon R, Yong CM, Chen J, et al.
    Asian Pac J Cancer Prev, 2018 Apr 25;19(4):933-940.
    PMID: 29693347
    Purpose: To comparatively evaluate the results of a 2-dose human papillomavirus (HPV) vaccination programme
    with the AS04-adjuvanted HPV16/18 vaccine (AS04-HPV-16/18v) or HPV-6/11/16/18 vaccine (4vHPVv), in addition
    to cervical cancer (CC) screening, in Malaysia. Methods: A lifetime Markov model replicating the natural history of
    HPV in 13-year-old girls was adapted to Malaysia to assess the impact of vaccination on pre-cancerous lesions, genital
    warts and CC cases, CC deaths, quality-adjusted life years (QALYs), and costs from the perspective of the Malaysian
    Ministry of Health. Vaccine effectiveness was based on efficacy and HPV type distribution. Both vaccines were assumed
    to have equal efficacy against vaccine-type HPV but differed for protection against non-vaccine types. Vaccine price
    parity was used and health and cost outcomes were discounted at 3%/annum. Sensitivity analyses tested the robustness
    of the results. Results: The model predicted that AS04-HPV-16/18v would result in 361 fewer CC cases and 115 fewer
    CC deaths than 4vHPVv, whereas 4vHPVv averted 4,241 cases of genital warts over the cohort’s lifetime. Discounted
    total costs showed savings of 18.50 million Malaysian Ringgits and 246 QALYs in favour of AS04-HPV-16/18v. In
    one-way sensitivity analyses, the discount rate was the most influential variable for costs and QALYs, but AS04-HPV-
    16/18v remained dominant throughout. A two-way sensitivity analysis to assess the longevity of cross-protection for both
    vaccines confirmed the base-case. Conclusions: In Malaysia, the use of AS04-HPV-16/18v, in addition to screening,
    was modelled to be dominant over 4vHPVv, with greater estimated CC benefits and lower costs.
    Matched MeSH terms: Human papillomavirus 16/drug effects*
  13. Abdullah NN, Daud S, Wang SM, Mahmud Z, Mohd Kornain NK, Al-Kubaisy W
    J Obstet Gynaecol, 2018 Apr;38(3):402-407.
    PMID: 29385850 DOI: 10.1080/01443615.2017.1379061
    This study aims to determine the acceptability of Human Papilloma Virus (HPV) self-sampling and the factors associated with willingness to buy HPV self-sampling kit in the future. A total of 164 women aged 28-60 years old from Obstetrics & Gynaecology clinics at a teaching hospital performed HPV self-sampling using the Digene HC2 DNA collection kit. After samples were taken, the participants were given self-administered questionnaires. The majority of the participants were Malay (93.9%), had attained tertiary education (65.2%) and were employed (70.1%). The acceptability was good. More than half of the participants felt that self-sampling was easy. Only 1.2% felt that the procedure was difficult to perform. Most reported no pain at all during the procedure (66.9%). The commonest concern was getting a good sample (90.1%). A number of Pap smears were found to be significantly associated with the willingness to buy the HPV self-sampling kit. HPV self-sampling has the potential to be included in the cervical cancer screening programme. Impact Statement What is already known on this subject: HPV self-sampling is acceptable in some developed and developing countries. It is acceptable because it was easy to perform with very minimal pain or discomfort. Studies on the acceptance of self-screening are needed to plan a policy on self-sampling in the future. What the results of this study add: Our study adds new findings to the body of knowledge on self-sampling in the local population. We found that more women are willing to do the self-sampling at the clinic rather than at home. Although more than 90% expressed willingness to do self-sampling in the future, only 70% of them were willing to purchase the kit. Cost is a potential barrier to women who have the interest to perform the self-sampling. Given the global economic challenges, cost is inevitably an important predictor that we have to consider. What the implications are of these findings for clinical practice and/or further research: Future research should examine women from the rural areas and those who are resilient to Pap smear screening. In clinical practice, clinicians should acknowledge that cost is a potential barrier for women who are willing to do self-sampling. Self-sampling could be an option for women with no financial constraint to buy the kit. However, clinicians should counsel women so that they can make an informed choice in determining their screening method.
    Matched MeSH terms: Human papillomavirus 16
  14. Rashid NN, Yusof R, Watson RJ
    Anticancer Res, 2014 Nov;34(11):6557-63.
    PMID: 25368258
    It is well-established that HPV E7 proteins, encoded by human papillomavirus (HPV) genes, frequently associated with cervical cancers bind avidly to the retinoblastoma (RB) family of pocket proteins and disrupt their association with members of the E2F transcription factor family. Our previous study showed that the repressive p130-dimerization partner, RB-like, E2F and multi-vulval class (DREAM) complex was disrupted by HPV16 E7 proteins in order to maintain the viral replication in CaSki cells. However, we would like to address whether the activator B-myb-DREAM complex is critical in regulating the replication and mitosis phase since our previous study showed increased B-myb-DREAM expression in HPV-transformed cell lines when compared to control cells.
    Matched MeSH terms: Human papillomavirus 16/pathogenicity
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