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Gynaecological Oncology
The Benefit of Human Papillomavirus Testing in Predicting Cervical Cancer
Albert Singer
1
and Ashfaq M Khan
2
1. Professor of Gynaecological Research, University College London, and Consultant Gynaecologist, Whittington Hospital NHS Trust;
2. Clinical Research Fellow, Whittington Hospital NHS Trust, and Clinical Lecturer, Department of Biomedical Science, University College London
Abstract
Human papillomavirus (HPV) is the cause of cervical cancer and as such is being used to detect the pre-cancerous stages of this disease.
HPV DNA is employed in three clinical applications: as a primary screening test, as a triage to detect women with minor cytological
abnormalities who may harbour the more severe stages of the pre-cancer and in the follow-up of women treated for the severe stages. It
is superior when compared with exfoliative cytology, and recent studies show that it is suitable for use in both the developed and the
developing world for detecting cervical cancer. More sophisticated tests using type-specific HPV will be increasingly used in the future to
monitor young women undergoing vaccination against cervical cancer.
Keywords
Human papillomavirus (HPV), cervical pre-cancer (cervical intra-epitelial neoplasia [CIN]), primary screening, HPV genotyping
Disclosure: Albert Singer has received payment for lectures and seminars from Digene Corporation (now Qiagen), and has been on that company’s lecturers’ panel for many
years. Ashfaq M Khan has no conflicts of interest to declare.
Received: 25 January 2009 Accepted: 9 March 2009
Correspondence: Albert Singer, Department of Women’s Health, Jenner Building, The Whittington Hospital, Highgate Hill, London, N19 5NF, UK.
E:
albert.singer@whittington.nhs.uk
Globally, cervical cancer is the second most common cause of At present, HPV DNA testing is useful in three clinical applications:
cancer death in women, and in many developing countries it
remains the leading cause of cancer death in women. Annually, • as a primary screening test (either as an adjunct or stand-alone);
approximately 500,000 women are diagnosed with invasive cervical • in the follow-up of women treated for high-grade CIN; and
cancer, and nearly half of them die. The incidence of cervical cancer • as a triage test to detect genuinely high-risk women who are
varies dramatically around the globe because of the availability of diagnosed with minor cytological abnormalities.
screening services in some regions but not in others. Women living
in much of sub-Saharan Africa are almost 10 times more likely to Primary Screening with
develop cervical cancer than women living in western Europe. Human Papillomavirus Testing
It is now well accepted that HPV DNA testing is more sensitive but
High-risk human papillomavirus (HPV), which is detected in 99.7% less specific than cytology at detecting high-grade CIN. HPV testing
of cervical cancers, is now considered necessary for the tends to be more sensitive when specimen sampling is performed
development, maintenance and progression of cervical intra- by the clinician compared with self-collection by the women.
epithelial neoplasia (CIN) to cervical cancer. There are more than Screening of women over 30 years of age tends to improve the
100 genotypes of HPV, of which 40 exhibit a tropism for the mucosa sensitivity of HPV testing because viral infections in this group are
of the anogenital tract. However, only 13 types (16, 18, 31, 33, 35, more likely to be persistent rather than transient in nature and
39, 45, 51, 52, 56, 58, 59 and 66) are considered to be involved in the are more directly related to the development of high-grade disease.
development of lower genital tract neoplasia. Other high-risk HPV testing can be used as a primary screening test adjunctively
genotypes rarely cause cancer. The highest prevalence is seen in with cytology, as in the US, or as a frontline screen followed by
women under 25 years of age, in whom the infections are transient, cytology or another biomarker to manage women who are HPV-
lasting on average six months with clearance in almost 90% of positive and negative on cytology.
women within three years.
Randomised controlled trials comparing cytology with the combined
It is evident from both meta-analysis and cross-sectional studies use of cytology and HPV testing have shown substantially increased
that HPV testing has a higher sensitivity than cytology in detecting sensitivity with the latter approach.
3,4
A recent meta-analysis by
high-grade cervical pre-cancer (CIN2–3). The high negative Arbyn et al. showed that the overall sensitivity of HPV testing with
predictive value (NPV) of HPV DNA testing has various potential hybrid capture (HC2, QIAGEN, previously Digene) for detecting high-
clinical utilities. Exfoliative cytology with adjunctive HPV DNA testing grade CIN was 89.3% (95% confidence interval [CI] 85.2–93.4%). The
has been found to have a higher NPV for the detection of CIN.
1,2
overall specificity of HC2 in excluding high-grade CIN was 87.8%
58 © TOUCH BRIEFINGS 2009
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