DISEASE-SPECIFIC CANCER CONTROL
88 CANCER CONTROL 2014
reducing the infrastructure required for primary screening,
and saving pelvic evaluation for those who are positive on an
HPV screening test. If a triage step is desired, VIA is a
valuable test that can be implemented for evaluation of the
high-risk HPV-infected group of women, although it is
recognized that using a test like VIA or Pap as triage will
result in some loss of overall sensitivity.24 Additionally, VIA as
a triage test will help to identify women suspected of having
invasive cancer and needing immediate referral for
specialized treatment. VIA will also identify women with
large intra-epithelial lesions who are not eligible for
cryotherapy and need to be referred for excisional
procedures.
Even though molecular tests have the highest sensitivity
for detection of precancer and cancer of the uterine cervix,
there are still some limitations for their introduction in
developing countries. The initial investment required for
implementing the technology is high, and countries would
require support for the start-up and introduction in a
population-based programme. This initial investment would
be outweighed by the potential for extending the interscreening interval in women with negative
results, since their
risk of precancer is minimal within the next decade. Another
challenge is the need for developing algorithms for screening
and management of women with positive HPV results. In
order to fill this gap, WHO recently released its new
guidelines for screening and treatment of cervical cancer17;
these guidelines propose different algorithms for screening
using HPV testing, and triage of the positive women using
diverse options such as VIA or Pap smear. It is the
responsibility of each country to determine which algorithm
is more suitable for their population.
What impact will HPV vaccine have on VIA
screening?
Although it has only been seven years since HPV vaccine
introduction started, there are already some early signs of an
impact on screening. In Australia, young women who received
all three doses of vaccine had nearly half the risk of a cervical
intraepithelial neoplasia grade 3 or higher (CIN3+) cervical
lesion compared to similar unvaccinated women.
25 In the
United States, the proportion of cervical lesions that had HPV
types 16 or 18 - the most oncogenic types - was 33% less
among vaccinated women than among unvaccinated
women.26 HPV type 16 generally accounts for 50% or more of
high-grade lesions; if these are prevented, screening
programmes will have considerably fewer screen-positive
women to treat and follow up. How soon the benefit will be
seen after vaccination starts depends on the age at which
screening is initiated. Countries that start screening younger
than age 30 will see a decline sooner, since HPV 16 is
associated more with early-onset lesions. Screening
programmes will be able to start later and screen less often as
the vaccinated cohort comes of age. Even with the crossprotection against HPV types not included in the vaccines27
and a new 9-valent vaccine that will probably become
available in the next year or two, screening will still be needed
for at least the next three or four decades until fully
vaccinated cohorts reach the age of highest risk.28
Because a vaccine will make high-grade precancerous
lesions much less common, it will also make screening by
visual methods (VIA or Pap) more difficult since positive tests
will be relatively rare, giving screeners much less experience
seeing positives. The lower incidence of precancer will, of
necessity, reduce the predictive value of positive screening
tests and increase the cost of identifying precancer.1
For programmes that vaccinate at age 10 or so and start
screening at age 30, as recommended by WHO, it will take 20
years after a vaccine is introduced before an impact on
screening will be seen and 30 years before an impact on
cervical cancer incidence and mortality is measurable. If we
do not increase screening services above the current levels,
we can expect to see 21 million cases of cervical cancer in the
next 30 years and 9 million deaths, nearly all of which are
avoidable by screening and precancer treatment.
Rationale for continuing to invest in VIA and
precancer treatment
Despite these advances in vaccination and more sensitive
molecular tests, it is clear that there are compelling reasons
for continuing and even accelerating the investment in
programmes based on VIA and precancer treatment. VIA is
an effective and feasible screening tool that can be used
where molecular tests are not yet widely available, starting
with once-in-a-lifetime screening and increasing frequency
Even though molecular tests have
the highest sensitivity for detection
of precancer and cancer of the
uterine cervix, there are still some
limitations for their introduction in
developing countries