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Human papillomavirus related diseases in Malaysians

Cheah PL

Malays J Pathol, 1994 Jun;16(1):15-7.
PMID: 16329570

The surge of information on the aetiological association of the human papillomavirus (HPV) with some epithelial tumours emanating from various centres has prompted the initiation of a large-scale retrospective study at the Department of Pathology, University Hospital Kuala Lumpur to determine the prevalence and importance of this virus in some epithelial tumours of Malaysian patients. A retrospective analysis of 100 cases of large cell non-keratinising carcinoma of the uterine cervix by in-situ hybridisation on archival formalin-fixed, paraffin-embedded tissue has revealed the presence of HPV type 16 in 47% and type 18 in 41% of cases. This gives an overall detection rate of 88% of the two HPV types most commonly encountered in cervical carcinomas. Except for the unusually high frequency of HPV 18 detected in the cases, the overall prevalence is comparable to that reported in studies from most other centres. Although this higher frequency of HPV 18 may be due to geographical variation, the selection of the large cell non-keratinising type of squamous cell cervical carcinoma for study remains a possible reason for this phenomenon. In comparison to cervical carcinomas, HPV appears to be uncommon in penile carcinomas and HPV 6 was detected in only 1 of 23 cases studied.

Matched MeSH terms: Papillomaviridae/isolation & purification
High-risk human papillomavirus infection in different histological subtypes of renal cell carcinoma

Farhadi A, Behzad-Behbahani A, Geramizadeh B, Sekawi Z, Rahsaz M, Sharifzadeh S

J Med Virol, 2014 Jul;86(7):1134-44.
PMID: 24700118 DOI: 10.1002/jmv.23945

Limited data exist regarding whether a high-risk human papillomavirus (HR-HPV) infection increases the risk of developing renal cell carcinoma. The aim of this study was to investigate whether HPV infection has a role in the pathogenesis or development of a certain histological subtype of renal cell carcinoma. Formalin-fixed paraffin-embedded (FFPE) specimens of 122 patients with histopathologically proven renal cell carcinoma and their respective peritumoral tissues were examined. The presence of HPV-DNA was determined by a combination of MY/GP+ consensus primers and HPV-16/18 type specific nested PCRs followed by direct sequencing. Catalyzed signal-amplified colorimetric in situ hybridization (CSAC-ISH) technique was applied to determine the physical status of viral genome. The expression of p16INK4a and HPV L1 capsid proteins was evaluated using immunohistochemistry. HPV genome was detected in 37 (30.3%) tumor specimens and their four (4.1%) corresponding peritumoral tissues. HPV-18 was the most common viral type identified followed by HPV-16 and 58. Immunoexpression of p16INK4a was detected in 24 (20.3%) cases. Data analysis showed a significant correlation between p16INK4a expression and the presence of HR-HPV DNA (P

Matched MeSH terms: Papillomaviridae/isolation & purification*
Fulltext Cost-effectiveness of HPV vaccination in the prevention of cervical cancer in Malaysia

Wan Puteh WP, Aljunid S

Asian Pac J Cancer Prev, 2010;11(1):79-90.
PMID: 20593935

INTRODUCTION: Cervical cancers (CC) demonstrate the second highest incidence of female cancers in Malaysia. The costs of chronic management have a high impact on nation's health cost and patient's quality of life that can be avoided by better screening and HPV vaccination.

METHODOLOGY: Respondents were interviewed from six public Gynecology-Oncology hospitals. Methods include experts' panel discussions to estimate treatment costs by severity and direct interviews with respondents using costing and SF-36 quality of life (QOL) questionnaires. Three options were compared i.e. screening via Pap smear; quadrivalent HPV Vaccination and combined strategy (screening plus vaccination). Scenario based sensitivity analysis using screening population coverage (40-80%) and costs of vaccine (RM 300-400/dose) were calculated.

RESULTS: 502 cervical pre invasive and invasive cervical cancer (ICC) patients participated in the study. Mean age was 53.3 +/- 11.2 years, educated till secondary level (39.4%), Malays (44.2%) and married for 27.73 +/- 12.1 years. Life expectancy gained from vaccination is 13.04 years and average Quality Adjusted Life Years saved (QALYs) is 24.4 in vaccinated vs 6.29 in unvaccinated. Cost/QALYs for Pap smear at base case is RM 1,214.96/QALYs and RM 1,100.01 at increased screening coverage; for HPV Vaccination base case is at RM 35,346.79 and RM 46,530.08 when vaccination price is higher. In combined strategy, base case is RM 11,289.58; RM 7,712.74 at best case and RM 14,590.37 at worst case scenario. Incremental cost-effectiveness ratio (ICER) showed that screening at 70% coverage or higher is highly cost effective at RM 946.74 per QALYs saved and this is followed by combined strategy at RM 35,346.67 per QALYs saved.

CONCLUSION: Vaccination increase life expectancy with better QOL of women when cancer can be avoided. Cost effective strategies will include increasing the Pap smear coverage to 70% or higher. Since feasibility and long term screening adherence is doubtful among Malaysian women, vaccination of young women is a more cost effective strategy against cervical cancers.

Matched MeSH terms: Papillomaviridae/isolation & purification
HPV infection and the alterations of the pRB pathway in oral carcinogenesis

Lim KP, Hamid S, Lau SH, Teo SH, Cheong SC

Oncol Rep, 2007 Jun;17(6):1321-6.
PMID: 17487385 DOI: 10.3892/or.17.6.1321

Inactivation of the retinoblastoma (pRB) pathway is a common event in oral squamous cell carcinoma particularly through the aberrant expression of the components within this pathway. This study examines the alterations of molecules within the pRB pathway by looking at the presence of homozygous deletions in p16(INK4A) and the expression patterns of pRB, cyclin D1 and CDK4, as well as the presence of human papillomavirus (HPV) in our samples. In our study, 5/20 samples demonstrated deletions of p16(INK4A) exon 1alpha. pRB overexpression was found in 20/20 samples, the expression was mainly observed in all layers of the epithelia, particularly in the basal layer where cells are actively dividing and aberrant pRB expression was found in 12/20 samples. Cyclin D1 and CDK4 overexpression was detected in 6/20 and 2/20 samples respectively in comparison to hyperplasias where both proteins were either not expressed or expressed at minimal levels (<10%). Strikingly, HPV was found to be present in all of our samples, suggesting that HPV plays a significant role in driving oral carcinogenesis. Notably, 17/20 of our samples showed more than one alteration in the pRB pathway, however, we did not find any significant relationship between the presence of HPV, homozygous deletion of p16(INK4A) and overexpression of pRB, cyclin D1 and CDK4. Collectively, this data demonstrates that alterations in the pRB pathway are a common event and involve the aberration of more than one molecule within the pathway. Furthermore, the involvement of HPV in all our samples suggests that HPV infection may play an important role in oral carcinogenesis.

Matched MeSH terms: Papillomaviridae/isolation & purification
Assessment of the reliability of a novel self-sampling device for performing cervical sampling in Malaysia

Latiff LA, Rahman SA, Wee WY, Dashti S, Andi Asri AA, Unit NH, et al.

Asian Pac J Cancer Prev, 2015;16(2):559-64.
PMID: 25684487

BACKGROUND: The participation of women in cervical cancer screening in Malaysia is low. Self-sampling might be able to overcome this problem.The aim of this study was to assess the reliability of self-sampling for cervical smear in our country.
MATERIALS AND METHODS: This cross-sectional study was conducted on 258 community dwelling women from urban and rural settings who participated in health campaigns. In order to reduce the sampling bias, half of the study population performed the self-sampling prior to the physician sampling while the other half performed the self-sampling after the physician sampling, randomly. Acquired samples were assessed for cytological changes as well as HPV DNA detection.
RESULTS: The mean age of the subjects was 40.4±11.3 years. The prevalence of abnormal cervical changes was 2.7%. High risk and low risk HPV genotypes were found in 4.0% and 2.7% of the subjects, respectively. A substantial agreement was observed between self-sampling and the physician obtained sampling in cytological diagnosis (k=0.62, 95%CI=0.50, 0.74), micro-organism detection (k=0.77, 95%CI=0.66, 0.88) and detection of hormonal status (k=0.75, 95%CI=0.65, 0.85) as well as detection of high risk (k=0.77, 95%CI=0.4, 0.98) and low risk (K=0.77, 95%CI=0.50, 0.92) HPV. Menopausal state was found to be related with 8.39 times more adequate cell specimens for cytology but 0.13 times less adequate cell specimens for virological assessment.
CONCLUSIONS: This study revealed that self-sampling has a good agreement with physician sampling in detecting HPV genotypes. Self-sampling can serve as a tool in HPV screening while it may be useful in detecting cytological abnormalities in Malaysia.

Matched MeSH terms: Papillomaviridae/isolation & purification*
Fulltext Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development

Kaur G, Balasubramaniam SD, Lee YJ, Balakrishnan V, Oon CE

Asian Pac J Cancer Prev, 2019 Oct 01;20(10):3043-3049.
PMID: 31653153 DOI: 10.31557/APJCP.2019.20.10.3043

OBJECTIVE: Minichromosome maintenance complex (MCM) proteins are essential for the process of DNA replication and cell division. This study aimed to evaluate MCM genes expression profiles and MCM2 protein in HPV-associated cervical carcinogenesis.
METHODOLOGY: MCM2, 4, 5 and 7 genes expression profiles were evaluated in three cervical tissue samples each of normal cervix, human papillomavirus (HPV)-infected low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC), using Human Transcriptome Array 2.0 and validated by nCounter® PanCancer Pathway NanoString Array. Immunohistochemical expression of MCM2 protein was semi-quantitatively assessed by histoscore in tissue microarrays containing 9 cases of normal cervix, 10 LSIL, 10 HSIL and 42 cases of SCC.
RESULTS: MCM2, 4, 5 and 7 genes expressions were upregulated with increasing fold change during the progression from LSIL to HSIL and the highest in SCC. MCM2 gene had the highest fold change in SCC compared to normal cervix. Immunohistochemically, MCM2 protein was localised in the nuclei of basal cells of normal cervical epithelium and dysplastic-neoplastic cells of CIN and SCC. There was a significant difference in MCM2 protein expression between the histological groups (P = 0.039), and histoscore was the highest in HSIL compared to normal cervix (P = 0.010).
CONCLUSION: The upregulation of MCM genes expressions in cervical carcinogenesis reaffirms MCM as a proliferative marker in DNA replication pathway, whereby proliferation of dysplastic and cancer cells become increasingly dysregulated and uncontrolled. A strong expression of MCM2 protein in HSIL may aid as a concatenated screening tool in detecting pre-cancerous cervical lesions.

Matched MeSH terms: Papillomaviridae/isolation & purification