Displaying publications 1 - 20 of 24 in total

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  1. Tay SK, Tay YK
    Aust N Z J Obstet Gynaecol, 2009 Jun;49(3):323-7.
    PMID: 19566569 DOI: 10.1111/j.1479-828X.2009.01000.x
    To investigate the prevalence of high-risk human papillomavirus (HPV) and its associated cytological abnormalities among women attending cervical screening clinics in southern Malaysia and Singapore.
    Matched MeSH terms: Alphapapillomavirus/genetics; Alphapapillomavirus/isolation & purification*
  2. Tan SC, Ismail MP, Duski DR, Othman NH, Ankathil R
    Biosci Rep, 2018 Apr 27;38(2).
    PMID: 29487170 DOI: 10.1042/BSR20171268
    Information on the prevalence and type distribution of human papillomavirus (HPV) among Malaysian women is currently limited. The present study therefore aimed to provide an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. Total DNA was isolated from the cervical cell specimens of 185 histopathologically confirmed cervical cancer patients and 209 cancer-free healthy females who were tested negative in a recent Pap test. Viral-specific DNA was subsequently amplified with biotinylated primers and hybridized to HPV type-specific probes via a proprietary "flow-through hybridization" process for determination of HPV genotype. It was demonstrated that 83.2% of the cervical cancer patients and none (0.0%) of the cancer-free females were positive for HPV infection. Among HPV-positive subjects, 14 different viral genotypes were observed, namely HPV16, 18, 31, 33, 35, 45, 52, 53, 58, 66/68, 73, 81, 82, and 84/26. A total of 91.6% of the HPV-positive subjects had single-type HPV infections and the remaining 8.4% were simultaneously infected by two HPV genotypes. The most common HPV infections found were HPV16 (35.7%), HPV18 (26.0%), HPV58 (9.1%), and HPV33 (7.1%) single-type infections, followed by HPV16 + HPV18 co-infections (5.2%). The study has successfully provided an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. These findings could contribute valuable information for appraisal of the impact and cost-effectiveness of prophylactic HPV vaccines in the Malaysian population.
    Matched MeSH terms: Alphapapillomavirus/genetics*
  3. Shilling H, Murray G, Brotherton JML, Hawkes D, Saville M, Sivertsen T, et al.
    Vaccine, 2020 01 29;38(5):1186-1193.
    PMID: 31767467 DOI: 10.1016/j.vaccine.2019.11.019
    INTRODUCTION: Australia has recently implemented major changes in cervical cancer prevention policies including introduction of primary human papillomavirus (HPV) screening starting at age 25, and replacement of the quadrivalent HPV vaccine with the nonavalent vaccine in the national school-based program. We assessed the feasibility and utility of conducting HPV testing in residual clinical specimens submitted for routine Chlamydia trachomatis screening, as a means of tracking HPV vaccine program impact among young sexually active women.

    METHODS: De-identified residual specimens from women aged 16-24 years submitted for chlamydia testing were collected from three pathology laboratories in Victoria and New South Wales. Limited demographic information, and chlamydia test results were also collected. Patient identifiers were sent directly from the laboratories to the National HPV Vaccination Program Register, to obtain HPV vaccination histories. Samples underwent HPV genotyping using Seegene Anyplex II HPV 28 assay.

    RESULTS: Between April and July 2018, 362 residual samples were collected, the majority (60.2%) of which were cervical swabs. Demographic data and vaccination histories were received for 357 (98.6%) women (mean age 21.8, SD 2.0). Overall, 65.6% of women were fully vaccinated, 9.8% partially, and 24.7% unvaccinated. The majority (86.0%) resided in a major city, 35.9% were classified in the upper quintile of socioeconomic advantage and chlamydia positivity was 7.8%.The prevalence of quadrivalent vaccine-targeted types (HPV6/11/16/18) was 2.8% (1.5-5.1%) overall with no differences by vaccination status (p = 0.729). The prevalence of additional nonavalent vaccine-targeted types (HPV31/33/45/52/58) was 19.3% (15.6-23.8%). One or more oncogenic HPV types were detected in 46.8% (95% CI 41.6-52.0%) of women.

    CONCLUSIONS: HPV testing of residual chlamydia specimens provides a simple, feasible method for monitoring circulating genotypes. Applied on a larger scale this method can be utilised to obtain a timely assessment of nonavalent vaccine impact among young women not yet eligible for cervical screening.

    Matched MeSH terms: Alphapapillomavirus/isolation & purification*
  4. Saville M, Hawkes D, Keung M, Ip E, Silvers J, Sultana F, et al.
    J Clin Virol, 2020 06;127:104375.
    PMID: 32361328 DOI: 10.1016/j.jcv.2020.104375
    BACKGROUND: In the last decade, human papillomavirus (HPV) testing has been evaluated extensively for cervical screening, with studies finding increased sensitivity compared to cytology. Another advantage of HPV based-screening is the ability to test vaginal samples that can be collected by women themselves. Self-collection has the potential to extend cervical screening coverage by increasing participation rates, particularly among women who are under-screened or have never screened. This could have a significant impact on cervical cancer prevention, as the majority of invasive cervical cancer cases occur among under-screened women. Both the Netherlands and Australia have transitioned their national programs from cytology to HPV as the primary screening test and both countries include a pathway for self-collection.

    OBJECTIVES: We evaluated the relative sensitivity for HPV detection of self-collection compared with practitioner-collected cervical specimens in the context of the Australian National Cervical Screening Program (NCSP).

    STUDY DESIGN: 303 women aged ≥18 years attending a single tertiary referral centre took their own sample using a flocked-swab, and then had a practitioner-collected sample taken at colposcopy. All samples were tested at a single laboratory on the six PCR-based HPV assays which can be utilised in the NCSP; Roche cobas 4800 and cobas, Abbott RealTime, BD Onclarity, Cepheid Xpert, and Seegene Anyplex.

    RESULTS: HPV16/18 results had high observed agreement between self- and practitioner-collected samples on all assays (range: 0.94-0.99), with good agreement for non-HPV16/18 oncogenic HPV types (range: 0.64-0.73).

    CONCLUSIONS: Self-collection for HPV-based cervical screening shows good concordance and relative sensitivity when compared to practitionercollected samples across assays in the NCSP.

    Matched MeSH terms: Alphapapillomavirus/isolation & purification
  5. Saini R, Osman NB, Ismail M, Sobri FM, Tang TH, Santhanam J
    J Investig Clin Dent, 2011 Nov;2(4):241-7.
    PMID: 25426895 DOI: 10.1111/j.2041-1626.2011.00068.x
      To determine the prevalence of human papillomavirus in the oral cavity of denture wearers.
    Matched MeSH terms: Alphapapillomavirus/classification; Alphapapillomavirus/isolation & purification*
  6. Saini R, Khim TP, Rahman SA, Ismail M, Tang TH
    Virol J, 2010;7:131.
    PMID: 20550718 DOI: 10.1186/1743-422X-7-131
    Association of High-risk Human Papillomavirus (HR-HPV) with oral cancer has been established recently. Detecting these viruses in oral cavity is important to prevent oral lesions related to them. The purpose of this study was to evaluate the prevalence of HR-HPV in the oral cavity of women with cervical cancer, and their children. A total of 70 women, previously diagnosed with cervical cancer, and 46 children of these women, born by vaginal delivery only, were selected for this study. Buccal swabs were collected from their oral cavity and HPV detection was carried out using Hybrid Capture 2 high-risk HPV (HC2 HR-HPV) detection system.
    Matched MeSH terms: Alphapapillomavirus/genetics; Alphapapillomavirus/isolation & purification*
  7. Saini R, Tang TH, Zain RB, Cheong SC, Musa KI, Saini D, et al.
    J Cancer Res Clin Oncol, 2011 Feb;137(2):311-20.
    PMID: 20419384 DOI: 10.1007/s00432-010-0886-8
    PURPOSE: The purpose of this study was to evaluate the role of HPV and p53 polymorphisms in oral squamous cell carcinomas (OSCC) affecting Malaysian population.

    METHODS: We analysed frozen samples from 105 OSCC as well as 105 oral specimens derived from healthy individuals. PCR assays targeting two regions of the virus were used. PCR amplification for the analysis of p53 codon 72 arginine/proline alleles was carried out in a separate reaction.

    RESULTS: HPV DNA was detected in 51.4% OSCC samples, while 24.8% controls were found to be HPV positive. HPV was found to be significantly associated with OSCC (P 

    Matched MeSH terms: Alphapapillomavirus/genetics; Alphapapillomavirus/isolation & purification*
  8. Rompalo A
    J Clin Invest, 2011 Dec;121(12):4580-3.
    PMID: 22133882 DOI: 10.1172/JCI61592
    Sexually transmitted infections (STIs) have plagued humans for millennia and can result in chronic disease, pregnancy complications, infertility, and even death. Recent technological advances have led to a better understanding of the causative agents for these infections as well as aspects of their pathogenesis that might represent novel therapeutic targets. The articles in this Review Series provide excellent updates on the recent advances in understanding of the pathogenesis of some very important and persistent STIs and discuss the importance of considering each pathogen in the broader context of the environment of the individual who it infects.
    Matched MeSH terms: Alphapapillomavirus
  9. Rajan S, Shen TH, Santhanam J, Othman NH, Othman N, Hock TT
    Trop Biomed, 2007 Jun;24(1):17-22.
    PMID: 17568373
    Human papillomavirus (HPV) is well known as an etiological factor for the development of anogenital carcinomas. The aim of our study was to compare the performance of USFDA approved Hybrid II (HCII) Assay and recently introduced DR. HPV Chip Kit for the detection of HPV DNA in clinical cervical scrapings from 40 patients. HPV DNA testing was performed using the automated HCII Assay system and DR. HPV Chip Kit. Taking cytological results as gold standard, it was found that HCII was more sensitive (36.4%) than DR. HPV Chip Kit (18.2%) although specificity was 100% with the latter method. In addition, both these molecular methods had comparable negative and positive predictive values. It was concluded that both HCII and DR. HPV Chip Kit have comparable specificity. However, sensitivity for detection of HPV in clinical samples with HCII is almost double as compared to DR. HPV Chip Kit.
    Matched MeSH terms: Alphapapillomavirus/isolation & purification*
  10. Nor Rashid N, Yong ZL, Yusof R, Watson RJ
    Virol J, 2016 Jan 04;13:2.
    PMID: 26728921 DOI: 10.1186/s12985-015-0460-8
    Retinoblastoma like protein 2 (RBL2) or p130 is a member of the pocket protein family, which is infrequently mutated in human tumours. Its expression is posttranscriptionally regulated and largely G0 restricted. We have previously shown that E6/E7 oncoproteins encoded by human papillomavirus (HPV) type 16, which is a high-risk type for cervical cancer development, must target p130 to promote the host cell to exit from quiescence (G0) state and enter S phase of the cell cycle. P130 is associated with the DREAM (DP, RB-like, E2F and MuvB) complex in G0/G1, which prevents S phase progression by repressing transcription of E2F-regulated genes. E7 proteins could potentially disrupt the p130-DREAM complex through two known mechanisms: direct interaction with p130 or induction of cyclin dependent kinase 2 (CDK2) phosphorylation by interacting with its inhibitor, p21(CIP1).
    Matched MeSH terms: Alphapapillomavirus/classification*; Alphapapillomavirus/metabolism*
  11. Lin Y, Su Z, Chen F, Zhao Q, Zimet GD, Alias H, et al.
    Hum Vaccin Immunother, 2021 01 02;17(1):304-315.
    PMID: 32401617 DOI: 10.1080/21645515.2020.1756152
    Little is known regarding Chinese mothers' intention to vaccinate their daughters against human papillomavirus (HPV) since the HPV vaccine was approved for use in China in 2016. The aim was to explore maternal HPV vaccination acceptance, preference for 2-, 4- or 9-valent HPV vaccine and acceptance of domestically manufactured HPV vaccines. Study participants were mothers of primary school children in Southeastern region of Fujian. An online cross-sectional survey was undertaken between June and August 2019. Among the total of 3,586 completed responses (response rate 28.5%), the intention to vaccinate daughter against HPV was high (83.3%). Higher maternal education and perceived benefit and barriers were associated with greater intention to vaccinate. Among mothers who did not intend to vaccinate their daughters, the three most common reasons were daughter being too young to receive HPV vaccination (40.6%), fear of side effects (31.9%) and vaccine price is too high (16.0%). The largest proportion (41.4%) preferred their daughter to be vaccinated with the 9-valent HPV vaccine (9vHPV). Greater preference for 9vHPVwas strongly associated with higher maternal education level and annual household income. The majority of mothers expressed a preference for imported HPV vaccine (56.3%). Our result indicates that lower intentions to vaccinate daughters against HPV among less educated and lower-income mothers may lead to significant social inequalities in HPV vaccine uptake in the country.
    Matched MeSH terms: Alphapapillomavirus*
  12. Li CK, Dalvi R, Yonemori K, Ariffin H, Lyu CJ, Farid M, et al.
    ESMO Open, 2019;4(3):e000467.
    PMID: 31231565 DOI: 10.1136/esmoopen-2018-000467
    Background: Adolescents and young adults (AYAs) with cancer require dedicated management encompassing both adult and paediatric cancer services. Following a European survey, the European Society for Medical Oncology, the European Society for Paediatric Oncology and the Asian continental branch of International Society of Paediatric Oncology undertook a similar survey to assess AYA cancer care across Asia.

    Methods: A link to the online survey was sent to healthcare professionals (HCPs) in Asia interested in AYA cancer care. Questions covered the demographics and training of HCPs, their understanding of AYA definition, availability and access to specialised AYA services, the support and advice offered during and after treatment, and factors of treatment non-compliance.

    Results: We received 268 responses from 22 Asian countries. There was a striking variation in the definition of AYA (median lower age 15 years, median higher age 29 years). The majority of the respondents (78%) did not have access to specialised cancer services and 73% were not aware of any research initiatives for AYA. Over two-thirds (69%) had the option to refer their patients for psychological and/or nutritional support and most advised their patients on a healthy lifestyle. Even so, 46% did not ask about smokeless tobacco habits and only half referred smokers to a smoking cessation service. Furthermore, 29% did not promote human papillomavirus vaccination for girls and 17% did not promote hepatitis B virus vaccination for high-risk individuals. In terms of funding, 69% reported governmental insurance coverage, although 65% reported that patients self-paid, at least partially. Almost half (47%) reported treatment non-compliance or abandonment as an issue, attributed to financial and family problems (72%), loss of follow-up (74%) and seeking of alternative treatments (77%).

    Conclusions: Lack of access to and suboptimal delivery of AYA-specialised cancer care services across Asia pose major challenges and require specific interventions.

    Matched MeSH terms: Alphapapillomavirus
  13. Khoo SP, Lim WT, Rajasuriar R, Nasir NH, Gravitt P, Woo YL
    Cancer Prev Res (Phila), 2021 01;14(1):105-112.
    PMID: 32917643 DOI: 10.1158/1940-6207.CAPR-20-0280
    Vaginal self-sampling for human papillomavirus (HPV) testing can potentially increase cervical screening coverage. This study aimed to investigate the acceptability of vaginal self-sampling for HPV testing and factors that might influence a woman's preference for this as a cervical screening method. This was a cross-sectional study that recruited 725 women from the urban and suburban areas of Selangor, Malaysia. All study participants were instructed to self-collect vaginal sample using a dry flocked swab before responding to a detailed questionnaire documenting their experience and preference for self-sampling. Most of the study participants (>80%) perceived vaginal self-sampling as easy, convenient, not embarrassing, comfortable, and were confident in performing the test. This suggests high acceptability toward vaginal self-sampling for HPV testing. Of the 725 women, 83% preferred self-sampling HPV testing over healthcare personnel sampling HPV testing and Pap test. Women with higher household income and full-time employment status were more likely to prefer self-sampling. Those who had not undergone Pap test also expressed preference for self-sampling HPV testing. Convenience and women's confidence in performing a vaginal self-sampling for HPV testing were the independent key factors that influenced the preference for self-sampling method. Vaginal self-sampling for HPV testing is highly acceptable among Malaysian women. It is the preferred choice as a primary cervical screening method and serves as an alternative to healthcare-acquired sample for Pap test. PREVENTION RELEVANCE: Organized cervical cancer screening remains unachievable in many countries. Self-sampling HPV testing is an evidence-based method that can remove barriers to cervical screening. This is particularly important for developing countries in order to achieve the WHO global strategy to accelerate cervical cancer elimination.
    Matched MeSH terms: Alphapapillomavirus/isolation & purification
  14. Khoo CL, Teoh S, Rashid AK, Zakaria UU, Mansor S, Salleh FN, et al.
    Asian Pac J Cancer Prev, 2011;12(6):1429-33.
    PMID: 22126476
    INTRODUCTION: As the second most common cancer in women worldwide, cervical cancer causes major health and economic burdens. Recent introduction of HPV immunization program locally has been encouraging but vaccine uptake remains poor. In addition, no study has been conducted to explore the people' s awareness and knowledge on cervical cancer, HPV and its vaccine in a rural setting in Malaysia after the inception of the HPV vaccination program.
    OBJECTIVE: This study was conducted to determine the awareness of cervical cancer, HPV vaccination and its affordability among people in a rural area in Malaysia.

    METHOD: A cross-sectional study was conducted among 116 participants in a village in Penang. All consenting female villagers aged 13 years and above, and males who were married were interviewed using a questionnaire.
    RESULTS: Most participants (88.8%) had heard of cervical cancer, however only 29.3% and 42.2% of them had heard of HPV and HPV vaccination respectively. Only 5.2% knew the actual market price for the vaccine. They were willing to pay an average of RM 96.7 (USD $27.7) for the full course of vaccination if it is not given to them for free, whereas the market price is RM1200 (USD $342.85).
    CONCLUSION: Awareness among the Malaysian population in a rural setting on HPV and HPV vaccination is low. Educating the public on the infection can help control the illness. Cost of the HPV vaccine is a serious barrier to the success of the vaccination program in Malaysia.
    Matched MeSH terms: Alphapapillomavirus
  15. Khairuddin N, Blake SJ, Firdaus F, Steptoe RJ, Behlke MA, Hertzog PJ, et al.
    Immunol Cell Biol, 2014 Feb;92(2):156-63.
    PMID: 24217808 DOI: 10.1038/icb.2013.75
    Small interfering RNAs (siRNAs) to inhibit oncogene expression and also to activate innate immune responses via Toll-like receptor (TLR) recognition have been shown to be beneficial as anti-cancer therapy in certain cancer models. In this study, we investigated the effects of local versus systemic delivery of such immune-stimulating Dicer-substrate siRNAs (IS-DsiRNAs) on a human papillomavirus (HPV)-driven tumour model. Localized siRNA delivery using intratumour injection of siRNA was able to increase siRNA delivery to the tumour compared with intravenous (IV) delivery and potently activated innate immune responses. However, IV injection remained the more effective delivery route for reducing tumour growth. Although IS-DsiRNAs activated innate immune cells and required interferon-α (IFNα) for full effect on tumour growth, we found that potent silencing siRNA acting independently of IFNα were overall more effective at inhibiting TC-1 tumour growth. Other published work utilising IS-siRNAs have been carried out on tumour models with low levels of major histocompatibility complex (MHC)-class 1, a target of natural killer cells that are potently activated by IS-siRNA. As TC-1 cells used in our study express high levels of MHC-class I, the addition of the immunostimulatory motifs may not be as beneficial in this particular tumour model. Our data suggest that selection of siRNA profile and delivery method based on tumour environment is crucial to developing siRNA-based therapies.
    Matched MeSH terms: Alphapapillomavirus/immunology*
  16. Keane A, Ng CW, Simms KT, Nguyen D, Woo YL, Saville M, et al.
    Int J Cancer, 2021 12 15;149(12):1997-2009.
    PMID: 34363620 DOI: 10.1002/ijc.33759
    The WHO has launched a global strategy to eliminate cervical cancer through the scale-up of human papillomavirus (HPV) vaccination, cervical screening, and cervical cancer treatment. Malaysia has achieved high-coverage HPV vaccination since 2010, but coverage of the existing cytology-based program remains low. Pilot studies found HPV self-sampling was acceptable and effective, with high follow-up rates when a digital registry was used, and recently the Malaysian Government announced plans for a national HPV-based screening program. We therefore evaluated the impact of primary HPV screening with self-collection in Malaysia in the context of Malaysia's existing vaccination program. We used the "Policy1-Cervix" modeling platform to assess health outcomes, cost-effectiveness, resource use and cervical cancer elimination timing (the year when cervical cancer rates reach four cases per 100 000 women) of implementing primary HPV testing with self-collection, assuming 70% routine-screening coverage could be achieved. Based on available data, we assumed that compliance with follow-up was 90% when a digital registry was used, but that compliance with follow-up would be 50-75% without the use of a digital registry. We found that the current vaccination program would prevent 27 000 to 32 200 cervical cancer cases and 11 700 to 14 000 deaths by 2070. HPV testing with a digital registry was cost-effective (CER = $US 6953-7549 
    Matched MeSH terms: Alphapapillomavirus/isolation & purification
  17. Islam JY, Gurbani A, Ramos S, Morgan K, Kim CJ, Richter KL, et al.
    Sex Transm Dis, 2021 Aug 01;48(8):557-564.
    PMID: 34014055 DOI: 10.1097/OLQ.0000000000001389
    BACKGROUND: National human papillomavirus (HPV) vaccination programs could reduce global cervical cancer morbidity and mortality with support from health care providers. We assessed providers' perceptions of HPV vaccination in 5 countries.

    METHODS: We identified providers from 5 countries where national HPV vaccination programs were at various stages of implementation: Argentina, Malaysia, South Africa, South Korea, and Spain. Providers authorized to administer adolescent vaccines completed an in-depth survey, reporting perceptions of barriers and facilitators to initiating and completing HPV vaccination, and logistical challenges to HPV vaccination.

    RESULTS: Among 151 providers, common barriers to HPV vaccination initiation across all countries were parents' lack of awareness (39%), concerns about vaccine safety or efficacy (33%), and cost to patients (30%). Vaccination education campaign (70%) was the most commonly cited facilitator of HPV vaccination initiation. Common barriers to series completion included no reminder system or dosing schedule (37%), loss to follow-up or forgetting appointment (29%), and cost to patients (25%). Cited facilitators to completing the vaccine series were education campaigns (45%), affordable vaccination (32%), and reminder/recall systems (22%). Among all countries, high cost of vaccination was the most common logistical challenge to offering vaccination to adolescents (33%).

    CONCLUSIONS: Incorporating provider insights into future HPV vaccination programs could accelerate vaccine delivery to increase HPV vaccination rates globally.

    Matched MeSH terms: Alphapapillomavirus*
  18. Hawkes D
    Med J Malaysia, 2021 09;76(5):718.
    PMID: 34508380
    No abstract provided.
    Matched MeSH terms: Alphapapillomavirus*
  19. Gravitt PE
    J Clin Invest, 2011 Dec;121(12):4593-9.
    PMID: 22133884 DOI: 10.1172/JCI57149
    The discovery that certain high-risk strains of human papillomavirus (HR-HPV) cause nearly 100% of invasive cervical cancer has spurred a revolution in cervical cancer prevention by promoting the development of viral vaccines. Although the efficacy of these vaccines has already been demonstrated, a complete understanding of viral latency and natural immunity is lacking, and solving these mysteries could help guide policies of cervical cancer screening and vaccine use. Here, we examine the epidemiological and biological understanding of the natural history of HPV infection, with an eye toward using these studies to guide the implementation of cervical cancer prevention strategies.
    Matched MeSH terms: Alphapapillomavirus/classification; Alphapapillomavirus/immunology; Alphapapillomavirus/physiology*
  20. Gandhi S, Nor Rashid N, Mohamad Razif MF, Othman S
    Mol Biol Rep, 2021 Jun;48(6):5121-5133.
    PMID: 34169395 DOI: 10.1007/s11033-021-06509-4
    The High-Risk Human Papillomaviruses (HR-HPVs) 16 and 18 are known to cause cervical cancer, which is primarily attributed to E6 and E7 oncoproteins. In addition, recent studies have focused on the vital role of the p130 pocket protein as an oncosuppressor to limit the expression of E2F transcription factors required for cell cycle progression. In view of this, the current study was conducted to investigate the mechanism by which transfection with HPV16/18 E7 leads to the deregulation of the host cell cycle, altering the localisation of p130, and expression of differentiation genes in Human Keratinocytes (HaCaT) cells. Co-immunoprecipitation, Western blot analysis, immunofluorescence microscopy, flow cytometry, quantitative-Polymerase Chain Reaction (qPCR), and the inhibition of p130 by MG132 inhibitor were employed to investigate the loss of p130 and its disruption in HPV 16/18 E7-transfected HaCaT cells. The HPV16- and HPV18-transformed cells, known as CaSki and HeLa, respectively, were also used to complement the ectopic expressions of E7 in HaCaT cells. Normal keratinocytes displayed higher level of p130 expression than HPV-transformed cells. In addition, the immunofluorescence analysis revealed that both HPV 16/18 E7-transfected HaCaT and HPV-transformed cells exhibited higher level of cytoplasmic p130 compared to nuclear p130. A significant increase in the number of S/G2 phase cells in HPV-transformed cells was also recorded since E7 has been shown to stimulate proliferation through the deactivation of Retinoblastoma Protein (pRB)-dependent G1/S checkpoint. Furthermore, the findings recorded the down-regulation of keratinocyte differentiation markers, namely p130, keratin10, and involucrin. The proteasomal degradation of the exported p130 confirmed the cellular localisation pattern of p130, which was commonly observed in cancerous cells. The findings provide strong evidence that the localisation of nuclear p130 nuclear was disrupted by HPV16/18 E7 led to the deregulation of the cell cycle and the impairment of cellular differentiation ultimately lead to cellular transformation.
    Matched MeSH terms: Alphapapillomavirus/genetics; Alphapapillomavirus/pathogenicity
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