SCIENCE REVIEW


Human papillomavirus: genomics and immunity


The human papillomavirus (HPV) is a pathogenic non-enveloped virus belonging to the family Papillomaviridae, and contains double-stranded DNA. It infects epithelial tissues, is transmitted by sexual contact, and is associated with cervical cancer and anogenital and oropharyngeal cancers. It is estimated that HPV infection is responsible for around 500,000 cases of cervical cancer and 275,000 deaths worldwide each year. The virus has a number of genotypes, and these are subdivided into low-risk and high-risk types, the latter resulting in a predisposition to cancerous transformation. The HPV16 and HPV18 subtypes are high-risk types because they express the oncoproteins E6 and E7 in target cells, and these contribute to cellular proliferation, differentiation and genomic instability, inducing malignant transformation. An Irish study (Keegan H, Ryan F, Malkin A, Griffin M, Lambkin H. Human papillomavirus prevalence and genotypes in an opportunistically screened female Irish population. Br J Biomed Sci 2006; 64 [1]: 1–5) evaluated HPV prevalence and predominating genotypes in liquid-based cervical cytology samples from a female urban Irish population. In addition, the cohort was screened for HPV using the MY09/11 primers for the HPV L1 gene and


Human papillomavirus (HPV) infection causes benign and malignant neoplastic lesions of the uterine cervical epithelium. Multiple HPV types are known to infect the anogenital region and these are classified as high-risk or low-risk according to their oncogenic potential. High-risk types 16 and 18 are the most common HPV types found in cervical carcinomas worldwide and much research has focused on these HPV types in the elucidation of the molecular mechanisms of cervical carcinogenesis. The majority of cervical HPV infections are


of high-risk type; however, the geographical distribution of HPV types other than HPV 16 and 18 varies considerably worldwide. Human papillomavirus is a ubiquitous


organism and it is estimated that approximately 80–85% of individuals will be infected during their lifetime. Human papillomavirus infections, most of which are transient, are most common in young adults, and persistent high-risk infection is the single most important risk factor in the development of cancerous and precancerous lesions. Precancerous cervical lesions are


screened by conventional Papanicolaou (Pap) smear examination and most developed countries have screening


THE BIOMEDICAL SCIENTIST MAY 2016


primers for β-globin amplification in a multiplex format. In 2012, a Portuguese group (Pereira A, Prata E, Nunes R. Understanding how HLA and KIR gene combinations can influence HPV infection. The Biomedical Scientist 2012 August; 56 [8]: 472–7) studied the effect of human leucocyte antigen (HLA) and gene combinations on HPV infection. Recently, groups working in the USA (Ambulos NP Jr, Schumaker LM, Mathias TJ et al. Next-generation sequencing-based HPV genotyping assay validated in formalin-fixed, paraffin-embedded oropharyngeal and cervical cancer specimens. J Biomol Tech 2016 Mar 7. pii: jbt.16- 2702-004 [Epub ahead of print]), France (Tamalet C, Halfon P, Retraite LL et al. Genotyping and follow-up of HR-HPV types detected by self-sampling in women from low socioeconomic groups not participating in regular cervical cancer screening in France. J Clin Virol 2016; 78:102–7) and Egypt (Youssef MA, Abdelsalam L, Harfoush RA et al. Prevalence of human papillomavirus [HPV] and its genotypes in cervical specimens of Egyptian women by linear array HPV genotyping test. Infect Agent Cancer 2016; 11: 6) have extended the literature on the genomic theme.


programmes in place. However, recently there has been a drive towards DNA-based testing for high-risk HPV as part of screening algorithms, as this substantially increases the sensitivity of detection of neoplasia.


Genotypes and opportunistic screening An Irish study (Keegan H, Ryan F, Malkin A, Griffin M, Lambkin H. Human papillomavirus prevalence and genotypes in an opportunistically screened female Irish population. Br J Biomed Sci 2006; 64 [1]: 1–5) evaluated HPV prevalence and predominating genotypes in liquid-based cervical cytology samples from a female urban Irish population. Importantly, the cohort was also screened for HPV using the MY09/11 primers for the HPV L1 gene


‘Human papillomavirus is a ubiquitous organism and it is estimated that approximately 80–85% of individuals will be infected during their lifetime’


and primers for β-globin amplification in a multiplex format. Overall, 996 women between the ages of


16 and 72 years were included in the study and HPV prevalence was 19.8%. Cytology results showed that 88.9% were normal, 9% borderline or mild dyskaryosis, 1.1% moderate dyskaryosis and 0.9% severe dyskaryosis. Human papillomavirus prevalence in women under 25 was 31%, reducing to 23% in women in the 25–35 age group and to 11% in women over 35. Human papillomavirus prevalence


increased with grade of cytology from 11.4% (normal), 85.4% (borderline), 84% (mild), 100% (moderate) to 100% (severe dyskaryosis). The genotypes HPV 16 (20%) and HPV 18 (12%) were the most common high-risk types detected in the study. Other common high-risk types were (in descending order) HPV 66, 33, 53, 31 and 58. HPV 66 was associated with the detection of borderline abnormalities by cytology. At the time of this study, the Republic of


Ireland was awaiting the full implementation of a national cervical screening programme. Thus, few data were available on HPV prevalence in the normal asymptomatic female Irish population, and thus the study


233


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60