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J Pathol. 1999 Sep;189(1):12-9.
Human papillomavirus is a necessary cause of invasive
cervical cancer worldwide.
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA,
Shah KV, Snijders PJ, Peto J, Meijer CJ, Mu?z N.
Department of Pathology, University Hospital Vrije
Universiteit, Amsterdam, The Netherlands. JMM.Walboomers@azvu.nl
A recent report that 93 per cent of invasive cervical
cancers worldwide contain human papillomavirus (HPV) may
be an underestimate, due to sample inadequacy or
integration events affecting the HPV L1 gene, which is
the target of the polymerase chain reaction (PCR)-based
test which was used. The formerly HPV-negative cases
from this study have therefore been reanalyzed for HPV
serum antibodies and HPV DNA. Serology for HPV 16 VLPs,
E6, and E7 antibodies was performed on 49 of the 66
cases which were HPV-negative and a sample of 48 of the
866 cases which were HPV-positive in the original study.
Moreover, 55 of the 66 formerly HPV-negative biopsies
were also reanalyzed by a sandwich procedure in which
the outer sections in a series of sections are used for
histological review, while the inner sections are
assayed by three different HPV PCR assays targeting
different open reading frames (ORFs). No significant
difference was found in serology for HPV 16 proteins
between the cases that were originally HPV PCR-negative
and -positive. Type-specific E7 PCR for 14 high-risk HPV
types detected HPV DNA in 38 (69 per cent) of the 55
originally HPV-negative and amplifiable specimens. The
HPV types detected were 16, 18, 31, 33, 39, 45, 52, and
58. Two (4 per cent) additional cases were only HPV
DNA-positive by E1 and/or L1 consensus PCR. Histological
analysis of the 55 specimens revealed that 21 were
qualitatively inadequate. Only two of the 34 adequate
samples were HPV-negative on all PCR tests, as against
13 of the 21 that were inadequate ( p< 0.001). Combining
the data from this and the previous study and excluding
inadequate specimens, the worldwide HPV prevalence in
cervical carcinomas is 99.7 per cent. The presence of
HPV in virtually all cervical cancers implies the
highest worldwide attributable fraction so far reported
for a specific cause of any major human cancer. The
extreme rarity of HPV-negative cancers reinforces the
rationale for HPV testing in addition to, or even
instead of, cervical cytology in routine cervical
screening.
   
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