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The Benefit of Human Papillomavirus Testing in Predicting Cervical Cancer
(95% CI 85.5–90%).
2
HPV testing showed better specificity in Europe a standardised and objective HPV DNA test for front-line primary
and North America. It is difficult to explain why the sensitivity was screening will likely provide better clinical sensitivity and
decreased in African and Asian countries. longer-term protection than either cytology or VIA. A newly
developed rapid HPV DNA test (careHPV Test, QIAGEN) provides
The HC2 HPV test is the only commercially available HPV test that is results in two hours and immediate treatment by cryotherapy of all
clinically validated by large-scale randomised controlled trials. It has women who are HPV-positive and/or have been diagnosed with
been used routinely for over 10 years now by clinicians across Europe disease by VIA could provide an effective alternative approach.
and around the world to identify women at highest risk of cervical Bearing this in mind, a milestone study just published
8
showed that
disease. Although the HC2 HPV test has been used routinely and a simple round of HPV testing using the HC2 system reduced the risk
employed in many clincal studies, there are also a number of other of advanced cervical cancer and deaths from this cancer by 50%
studies that have used the polymerase chain reaction (PCR)-based compared with cytology and VIA.
test. PCR technology provides a high analytical sensitivity to detect low
levels of HPV DNA infection, but has a lower sensitivity when detecting
clinically relevant infections. This reduced clinical sensitivity offers a
The negative predictive value of human
slightly improved specificity. Reproducibility is also often highly
papillomavirus (HPV) DNA testing has
variable, with intra- and inter-laboratory variability. A meta-analysis
showed a pooled sensitivity for detection of CIN2+ using PCR of 80.9%
potential clinical utility in following up
(95% CI 70–91.7%) and specificity of 94.7% (95% CI 92.5–96.9%).
5
treated cervical intra-epitelial neoplasia
The combination of HPV DNA testing (HC2) used adjunctively with
patients: women who are HPV-negative
cytology, which is becoming the standard of care in the US for all
after treatment are at very low risk of
women above 30 years of age, offers nearly 100% sensitivity.
Guidelines and recommendations are also published in Germany for
having residual or recurrent disease.
the use of HPV plus cytology every two years. This combination of
tests can detect CIN2+ in 99.2% of cases. The combination of tests Human Papillomavirus Testing as
has a high NPV, offers longer-term protection and could allow Follow-up After Treatment of
increased time intervals between screening (up to a three- to five- Cervical Intra-epithelial Neoplasia
year interval). However, the low specificity may still produce a high The main purpose of follow-up after treatment of CIN is to detect
number of false-positives and, subsequently, unnecessary referrals to residual or recurrent disease. The recurrence rate of cervical
colposcopy clinics. A developed country can support the extra costs pre-cancer after treatment is about 5–10%. Follow-up is
and infrastructure required for a combined HPV plus pap screening recommended for up to 10 years; the rationale behind such a long
programme because, in the long run, intervals can be extended in follow-up is the increased risk of developing CIN or cancer throughout
women who are double-negative, which will ultimately save on costs. this time period – or even longer – compared with a normal cohort.
The majority of treatment failures are due to residual disease, which
can be detected by cytology within two years of treatment. However,
the high NPV of HPV DNA testing alone also has potential clinical
The combination of human
utility in following up treated CIN patients: women who are HPV-
papillomavirus DNA testing (HC2) used
negative after treatment are at very low risk of having residual or
recurrent disease.
adjunctively with cytology, which is
becoming the standard of care in the
A recent multicentre prospective study evaluated the role of HPV
testing in combination with cytology in the follow-up of treated
US for all women above 30 years of
women.
9
The cumulative risk of residual disease was so low after 24
age, offers nearly 100% sensitivity.
months of follow-up that the authors suggested that women who are
cytology-negative and HPV-negative at six-month follow-up can safely
be recalled at three-year intervals rather than undergoing yearly
A recent study
6
proved this point when it was shown that in a general cytology for 10 years, as currently recommended. Interestingly, the
screening programme of 800,000 women, concerns about excessive NPV of the combination test results was similar in women with
HPV tesing in women above 30 years of age were not borne out. incomplete and complete excision margins in the original operative
specimens. This suggests that HPV status is a more important risk
However, in the developing world, where incidence and mortality factor than margin status with regard to residual disease.
rates are highest, it is difficult to implement cytology-based
screening programmes due to the lack of resources. Moreover, A large meta-analysis showed the sensitivity of HPV DNA testing in
multiple visits to colposcopy units from remote areas present a predicting treatment failure to be 94.4% (95% CI 90.9–97.9%), with a
major practical problem. Alternative methods have been specificity of 75% (95% CI 68.7–81.4%).
10
Unfortunately, the specificity
investigated such as employing visual inspection of the cervix with was statistically very heterogeneous among the groups. Nonetheless,
the application of acetic acid (VIA). This technique has been shown these data suggested that HPV testing has a higher sensitivity but
to reduce cancer incidence in low-resource settings. However, its similar specificity compared with cytology in detecting residual
sensitivity and specificity are not high enough to consider it a disease.
2
Other studies have suggested that combined cytology and
suitable long-term screening method. In such areas,
7
the use of HPV DNA testing is more effective than either test alone.
11,12
EUROPEAN OBSTETRICS & GYNAECOLOGY 59
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