Correspondence
test performance is dependent on 2 Qiao YL, Sellors JW, Eder PS, et al. A new
the operator and on locality-specific
effectiveness of quality management.4
From this perspective, the Mexico
study1 represents a comparison
of two different sets of largely
uncharacterised quality-management
methods.
Because cytology will remain part of
HPV-based screening programmes,4
we encourage Lazcano-Ponce and
colleagues to consider whether the
quality management parameters
(eg, salaries, training, equipment,
supplies, process measurements)
that were effective in their Qiagen-
supported HC2 laboratory will also
be effective in Mexican cytology
laboratories. The disappointing per-
formance of some Mexican cytology
laboratories1 could be rooted in
factors that will similarly affect
Mexican HC2 laboratories that lack
transnational support.
These issues could have problematic
implications for population coverage,
given the substantial added expense
of HC2, and evidence suggests that
increasing population coverage is
a more crucial challenge in Mexico
than is the optimisation of screening
test performance. Between 1990 and
2006, cytological screening was asso-
ciated with a 45% reduction in deaths
related to cervical cancer,5 despite only
30% population coverage in 2000 and
40% in 2005.
We declare that we have no conflicts of interest.
*Eric J Suba, Ludwig Erick González-Mena,
Myrna D Arrecillas-Zamora,
Stephen S Raab
eric.suba@kp.org
Department of Pathology, Kaiser Permanente
Medical Center, San Francisco, CA 94115, USA (EJS);
Laboratorio de Citología, Hospital General de
México OD, Universidad Nacional Autónoma de
México, México DF, México (LEG-M, MDA-Z);
Department of Laboratory Medicine, University of
Washington, Seattle, WA, USA (SSR); and Memorial
University of Newfoundland/Eastern Health
Authority, St John’s, NL, Canada (SSR)
1 Lazcano-Ponce E, Lorincz AT, Cruz-Valdez A,
et al. Self-collection of vaginal specimens for
human papillomavirus testing in cervical
cancer prevention (MARCH): a
community-based randomised controlled trial.
Lancet 2011; 378: 1868–73.
1588
shows that HPV testing improves
HPV-DNA test for cervical-cancer screening in
developing regions: a cross-sectional study of
clinical accuracy in rural China. Lancet Oncol
2008; 9: 929–36.
3 Sankaranarayanan R, Nene BM, Shastri SS,
et al. HPV screening for cervical cancer in rural
India. N Engl J Med 2009; 360: 1385–94.
4 Suba EJ, Raab SS; Viet/American Cervical
Cancer Prevention Project. Lessons learned
from successful Papanicolaou cytology cervical
cancer prevention in the Socialist Republic of
Vietnam. Diagn Cytopathol 2012; 40: 355–66.
5 Secretaría de Salud, Centro Nacional de
Equidad de Género y Salud Reproductiva.
Programa de acción específico, 2007-2012:
cáncer cérvicouterino. http://www.cnegsr.gob.
mx/programas/cancer-cervico-uterino/interes-
cacu/pa-cacu.html (accessed Dec 2, 2011).
Authors’ reply
Eric Suba and colleagues claim that
published studies from China and
India contradict the findings of our
MARCH randomised clinical trial, yet
the quoted trial from India1 found that
human papillomavirus (HPV) screen-
ing, but not cytology, reduced cervical
cancer mortality. In the other study
from China,2 hybrid capture 2 (HC2)
HPV testing was clearly more sensitive
than was cytology.
Our teams have long studied existing
screening programmes in cooperation
with the Mexican Government. In our
experience, screening with cytology
requires expensive infrastructure
and frequent repetition of invasive
sampling. By contrast, HPV testing
is more sensitive and cost-effective,
requires fewer screening rounds,
and can be adapted to self-collected
specimens. Our cost-effectiveness
studies show that HPV testing is
superior to cytology when real-world
input data and realistic prices are used.3
We have also assisted in major efforts
to increase screening coverage, leading
to about 8·5 million cytology tests
in 2011. Yet according to our recent
audit,4 only 63 cancers were detected
by the latest 1 400 000 cytologies
from women older than 25 years, at a
cost of about US$20 million—quite a
poor performance.
As the first randomised clinical trial
comparing a simpler vaginal self-
collection approach versus clinic-based
cervical cytology, our MARCH study
acceptability, increases coverage, and
detects significantly more cancers.
Suba and colleagues are correct
that our comparison of strategies
represents a particular time and place
with many uncharacterised variables.
Scale-up of a new system is difficult
and might not reflect the success seen
in the trial; however, issues of scale
affect the implementation of all new
improvements in screening systems
and should not preclude progress.
Finally, Suba and colleagues suggest
that improvements in Papanicolaou
cytology coverage are the best way
to reduce cervical cancer mortality in
Mexico—a perspective with which we
disagree. They claim that our assess-
ment of cytology was unfair and that
cytology is effective in Mexico, quoting
statistics derived from our earlier work
that used a probabilistic model.5 This
study showed that cervical cytology
in Mexico seems to have contributed
to a modest decrease in mortality
from cervical cancer; however, other
potential factors implicated in the
decline are a decrease in birth rates
and an increase in economic indicators
such as gross national product.
We see as the biggest challenge for
Latin American countries the imple-
mentation of organised programmes
to allow effective follow-up of women
with HPV infection and cytological
abnormalities.
We declare that we have no conflicts of interest
other than those stated in the original paper.
*Attila Tibor Lorincz,
Eduardo Lazcano-Ponce
a.lorincz@qmul.ac.uk
Centre for Cancer Prevention, Wolfson Institute of
Preventive Medicine, Barts and the London School
of Medicine, Queen Mary University of London,
London EC1M 6BQ, UK (ATL); and Centro de
Investigación en Salud Poblacional, Instituto
Nacional de Salud Pública, Cuernavaca, Morelos,
Mexico (EL-P)
1 Sankaranarayanan R, Nene BM, Shastri SS,
et al. HPV screening for cervical cancer in rural
India. N Engl J Med 2009; 360: 1385–94.
2 Qiao YL, Sellors JW, Eder PS, et al. A new
HPV-DNA test for cervical-cancer screening in
developing regions: a cross-sectional study of
clinical accuracy in rural China. Lancet Oncol
2008; 9: 929–36.
www.thelancet.com Vol 379 April 28, 2012

3 Flores YN, Bishai DM, Lorincz A, et al. HPV testing
for cervical cancer screening appears more
cost-effective than Papanicolau cytology in
Mexico. Cancer Causes Control 2011; 22: 261–72.
4 Instituto Nacional de Salud Publica and Centro
Nacional de Equidad e Genero y Salud
Reproductiva. Evaluación del programa de
Prevención y Control del Cáncer Cervical en
México, 2008–2011: problemas y
recomendaciones. http://www.insp.mx/
images/stories/Centros/cisp/Docs/120412_
cneg.pdf (accessed April 13, 2012).
5 Lazcano-Ponce E, Palacio-Mejia LS,
Allen-Leigh B, et al. Decreasing cervical cancer
mortality in Mexico: effect of Papanicolaou
coverage, birthrate, and the importance of
diagnostic validity of cytology.
Cancer Epidemiol Biomarkers Prev 2008;
17: 2808–17.
Surfactant treatment for
spontaneously breathing
preterm infants
Wolfgang Göpel and colleagues
(Nov 5, p 1627)1 deserve kudos for
their novel method of administering
surfactant.
However, there is no information
on age at randomisation and number
of patients intubated at baseline. In
supplementary table 2, whether values
for continuous positive airway pressure
(CPAP) at 1 and 12 h of life were baseline
variables or outcome variables is not
clear. If these were post-randomisation
variables, the subgroup analysis is clearly
inappropriate. However, if CPAP status
was a baseline variable as claimed, it
means that at 1 h, 10·2% and 25·9%
were mechanically ventilated in the
intervention and standard treatment
groups, respectively (p=0·003). At
12 h, 19·4% and 35·7% were mech-
anically ventilated in the intervention
and standard treatment groups,
respectively (p=0·007). There is an
imbalance in the proportion ventilated
at baseline, suggesting that patients
in the standard treatment group had
more severe disease than those in the
intervention group.
Previous surfactant treatment
with intubation was not an exclusion
criterion. How many patients in each
group had received surfactant with
intubation before randomisation?
www.thelancet.com Vol 379 April 28, 2012
Patients in the intervention group
received 100 mg/kg of surfactant. Did
any patient in the standard treatment
group receive 200 mg/kg as the first
dose of poractant?2
It would be interesting to know
whether there were differences be-
tween patients getting poractant
and beractant via catheter in terms
of the lowest heart rate and lowest
peripheral oxygen saturation reached
during administration. Differences
could affect the generalisability of the
findings to units that predominately
use beractant.
I declare that I have no conflicts of interest.
Sourabh Dutta
sdutta@mcmaster.ca
Department of Pediatrics, McMaster University
Medical Centre, Hamilton, ON L9K 1S7, Canada
1 Göpel W, Kribs A, Ziegler A, et al. Avoidance of
mechanical ventilation by surfactant
treatment of spontaneously breathing
preterm infants (AMV): an open-label,
randomised, controlled trial. Lancet 2011;
378: 1627–34.
2 Ramanathan R, Rasmussen MR,
Gerstmann DR, et al. A randomised,
multicentre masked comparison trial of
poractant alfa (Curosurf) versus beractant
(Survanta) in the treatment of respiratory
distress syndrome in preterm infants.
Am J Perinatol 2004; 21: 109–19.
Authors’ reply
Sourabh Dutta has some concerns
about the status of patients at entry
into the Avoiding Mechanical Ventil-
ation (AMV) trial.1 By contrast with
other studies—eg, the COIN trial,2 which
excluded infants who needed intubation
in the first minutes of life—we included
patients irrespective of their respiratory
status. This meant that eventually only
60% of all infants in the intervention
group received surfactant by gastric
tube. Some infants were intubated and
ventilated directly after delivery, and
others never reached the threshold of
30% oxygen saturation (see original
figure 11). A similar design has also been
chosen for the SUPPORT trial,3 since it
allows us to get an idea of how many
infants of a given gestational age might
benefit from such a procedure.
In light of similar questions that
arose during the review process,4 we
Correspondence
did a secondary analysis of respiratory
support at different times, and reported
it in the webappendix. Intubation rate
is expected to be higher in the standard
treatment group from 1 h to 12 h after
birth, because respiratory distress
syndrome will often develop within the
first 12 h and intubation is the only way
to deliver surfactant in these infants.
Concerning the surfactant dose
delivered, 100 mg/kg was given, as per
the design of the study, to all infants
in the intervention group and to 99%
in the standard treatment group. Only
a single child received the intervention
after an initial standard treatment.
Differences between different sur-
factant preparations and doses have
been discussed elsewhere.5 However,
we found no differences between
surfactant preparations in terms of
effects or side-effects (median lowest
heart rate: 133/min, IQR 120–155
on poractant; 150/min, 138–177 on
Science Photo Library
beractant; median lowest oxygen
saturation: 80%, 70–86 on poractant;
77%, 70–85 on beractant). Although
the absolute numbers of infants who
received different surfactants in our
study were too small to allow valid
conclusions to be drawn, the procedure
was well tolerated with 4 mL/kg
beractant (25 g/L) as well as 1·25 mL/kg
poractant (80 g/L phospholipids).
We declare that we have no conflicts of interest
other than those stated in the original paper.
*Egbert Herting, Christoph Härtel,
Angela Kribs, Bernhard Roth,
Wolfgang Göpel
herting@paedia.ukl.mu-luebeck.de
University of Lübeck, 23538 Lübeck, Germany
(EH, CH, WG); and University of Cologne, Cologne,
Germany (AK, BR)
1 Göpel W, Kribs A, Ziegler A, et al. Avoidance of
mechanical ventilation by surfactant treatment
of spontaneously breathing preterm infants
(AMV): an open-label, randomised, controlled
trial. Lancet 2011; 378: 1627–34.
2 Morley CJ, Davis PG, Doyle LW, et al. Nasal
CPAP or intubation at birth for very preterm
infants. N Engl J Med 2008; 358: 700–08.
3 Support Study Group of the Eunice Kennedy
Shriver NICHD Neonatal Research Network. Early
CPAP versus surfactant in extremely preterm
infants. N Engl J Med 2010; 362: 1970–79.
4 Cools F. A new method of surfactant
administration in preterm infants. Lancet
2011; 378: 1607–08.
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