Better triage tests needed for HPV positive women
Pedro Vieira-Baptista1,2,3
1. Hospital Lusíadas Porto, Porto, Portugal
2. LAP, Unilabs, Porto, Portugal
3. Lower Genital Tract Unit, Centro Hospitalar de São
João, Porto, Portugal
Email: pedrovieirabaptista@gmail.com
Tidy et al showed that 1/3 of all referrals for colposcopy, in
settings where primary high-risk HPV (HR-HPV) test is used for
screening, are due to positive tests with a negative triage cytology
(BJOG 2020 xxxx). These represent a significant burden of colposcopies
but yield a relatively low number of cases of CIN2+ (7%), translating a
low positive predictive value (PPV) of this approach.
Before generalizations of the results of this study can be made, some
particularities of the English cervical cancer screening program must to
be accounted for: 1) any HR-HPV positive test (including HPV16 and 18)
is subjected to triage with cytology; 2) there is an ongoing organized
screening program since 1988. In many countries, HPV16/18 positive women
are directly referred for colposcopy. An organized screening, with a
good coverage rate, even if cytology based, leads to a significant
reduction in the prevalence of disease – the near absence of CIN2+
encountered in older women is not a reality for most countries.(Mendes Det al. European Journal of Public Health . 2018; 2:343–7) In its
absence, the incidence of cervical cancer is bimodal, with the second
peak at the age of 60-69.
The rate of CIN2+ decreased steadily, as age increased: from 14.2% in
the group aged 25-34 years to absent in those >65 years. In
the first group, most cases were due to HPV16, while it lost importance
with increasing age. The PPV of colposcopy was lower in those positive
for non 16 HR-HPV. Additionally, the rate of non-visualization of the
squamo-colunar junction (SCJ) increased with age. Low rate of disease,
dominance of non 16 HR-HPV genotypes and non-visualization of the SCJ
contributed to a decline in the role and performance of colposcopy in
older women (in this equation the poorer performance of cytology in
older women is not being considered).
A minority of the women were likely to have been vaccinated against HPV.
As vaccinated women enter screening, the rate of HPV16 and 18 will drop
significantly in the younger cohorts. Putting in perspective: less
HPV16/18 and less CIN2/3, that is, a scenario comparable to the one
described in this paper for older women. The remaining CIN2/3, even in
younger women, will be attributable to genotypes of lower risk, thus
less likely to progress.
We are reaching a point, in adequately vaccinated and screened
populations, in which we must question ourselves whether we want to find
all CIN2/3 or just the ones that are likely to progress. As HPV16 and 18
become rarer, this will be a more and more a burning question. Finding
the right CIN2/3 is more important than finding all of them! The burden
associated with colposcopies and treatments cannot be ignored.
HPV will maintain its role in screening (probably with more extended
genotyping), as its sensitivity is unaffected by the decrease in
prevalence of disease. Nevertheless, more specific tests, unaffected by
the hormonal status or genotype, will be needed for triage (i.e.
methylation markers). Until the day prevalence becomes so low that
screening is not cost-effective…
Disclosure of interests: Received speaker fees from
Merck®, Roche®, Gedeon
Richter®, Seegene® Received
investigation grant from Seegene®. A completed disclosure of interest
form is available to view online as supporting information.