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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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