E lia n e P e d ra D ia s , J o s e M a ria P in to B a rc e /o s , M a ria E v a n g e lin a F e rre ira F o n s e c a , N a d ia G o m e s d a S ilv a B a s s o
C o n g e n ita l p a p illo m a s a n d p a p illo m a to s e s a s s o c ia te d w ith
th e H u m a n P a p illo m a V ir u s ( H P V ) • r e p o r t o n 5 c a s e s
Pathology Department
of UFF, Pathology Department of UNIRIO,
Virology Department
of UFRJ,
Clinical Pathology of IFF/FIOCRUZ
- Rio de Janeiro, Brazil
T h e a u th o rs p re s e n t a s tu d y o f fiv e c a s e s o f v u lv a r c o n g e n ita l p a p illo m a s a n d p a p illo m a to s e s in s tillb o rn s a n d n e o n a te s d e a d u p o n b irth . T h e s tu d ie d m a te ria l w a s c o lle c te d fro m fiv e n e c ro p s ie s . T h e h is to p a th o lo g ic a l e v a lu a tio n s h o w e d h y p e rk e ra to s is , a c a n th o s is , p a p illo m a to s is , p e rin u c le a r h a lo e s , a n d n u c le a r a b n o rm a litie s . In th re e o f th e c a s e s , th e e le c tro n m ic ro s c o p y id e n tifie d n u c le a r a n d c y to p la s m a tic v ira l p a rtic le s ra n g in g fro m 4 0 to 6 0 n m in s iz e , c o m p a tib le w ith H P V . T h e im m u n o h is to c h e m ic a l s tu d y o f th o s e le s io n s s h o w e d n u c le a r a n d c y to p la s m a tic p o s itiv ity . T h e a u th o rs c o n c lu d e d th a t th e p re s e n c e o f v ira l p a rtic le s s u g g e s tiv e o f H P V a d d e d to th e im m u n o p o s itiv ity in d ic a te d th e p o s s ib ility o f v ira l in fe c tio n .
U N IT E R M S : C o n g e n ita l P a p illo m a . H P V . P a p illo m a to s is .
IN T R O D U C T IO N
T
h eb e n i g nH u m a na n d m a l i g n a n tP a p i l l o m a l e s i o n s i n t h e s k i n a n d m u c o s a sV i r u s ( H P V ) i s a s s o c i a t e d t o ( 1 - 4 ) . O n e o f t h e w a y s t h e i n f e c t i o n p r e s e n t s i t s e l f i st h e c o n d y l o m a a c u m i n a t a , w h i c h c a n b e i n d u c e d b y t y p e s 6 ,
I I , 1 6 , 1 8 , a n d 5 4 ( 3 ) . T h e a p p e a r a n c e o f a n o g e n i t a l p a p i l l o m a s i n c h i l d r e n i s n o t f r e q u e n t . S i n c e 1 9 8 2 , o n l y 3 4
c a s e s o f i n f a n t c o n d y l o m a a c u m i n a t a w e r e p u b l i s h e d ( 5 ) . T h e
w a y s o f t r a n s m i s s i o n i n d i c a t e d w e r e p e r i n a t a l , f a m i l y c o n t a c t ,
a n d s e x u a l a b u s e .
T h e c o n g e n i t a l i n f e c t i o n b y H P V w a s s u g g e s t e d i n 1 9 7 8 ,
b y T a n g e t a l . ( 6 ) , w h e n t h e y r e p o r t e d a c o n d y l o m a a c u m i n a t a
c a s e o f a n e w b o r n w h o s e m o t h e r h a d a l e s i o n d u r i n g
p r e g n a n c y .
I n t h e 8 0 's , t h e n u m b e r o f p u b l i c a t i o n s c o n c e r n i n g t h e
c o n d y l o m a a c u m i n a t a i n c h i l d r e n g r e w s i g n i f i c a n t l y ( 7 - 2 0 ) .
A d d r e s s fo r c o r r e s p o n d e n c e : E lia n e P e d ra D ia s
R u a B a ra o d e Ita p a g ip e , 4 0 1 - b lo c o 2 -a p . 2 0 1 - T iju c a R io d e J a n e iro /R J - B ra s il- C E P 2 0 2 6 1 -0 0 0
I n t h e s e s t u d i e s , t h e m a i n m o d e o f t r a n s m i s s i o n c o n t i n u e d t o
b e s e x u a l a b u s e a n d p e r i n a t a l i n f e c t i o n . T y p e s 6 a n d
I I
a r ep r e d o m i n a n t i n t h e i n f a n t l e s i o n s , h o w e v e r , t y p e 2 w a s a l s o
i n d i c a t e d a s a n e t i o l o g i c a g e n t . B e s i d e s , t h e i d e n t i f i c a t i o n o f
t y p e s 1 6 a n d 1 8 , b o t h h a v i n g a n o n c o g e n i c p o t e n t i a l , r e i n f o r c e s
a l l t h e m o r e t h e i m p o r t a n c e o f f e t a l a n d i n f a n t i n f e c t i o n .
P r e g n a n c y s e e m s t o f a v o r t h e m a n i f e s t a t i o n o f t h e
c o n d y l o m a a c u m i n a t a s i n c e i t o c c u r s m o r e i n p r e g n a n t w o m e n
t h a n i n t h e g e n e r a l p o p u l a t i o n ( 2 1 - 2 3 ) .
U p u n t i l t h e e n d o f t h e 8 0 's , t h e m a j o r c o n c e r n a b o u t
w o m e n t h a t p r e s e n t e d c o n d y l o m a t a a c u m i n a t a d u r i n g d e l i v e r y ,
w a s t h e t r a n s m i s s i o n t o t h e f e t u s d u r i n g b i r t h a n d t h e p o s s i b l e
a p p e a r a n c e o f l a r y i n g e a l p a p i l l o m a t o s i s l e s i o n s ( 2 4 - 2 7 ) .
S e v e r a l s t u d i e s s h o w t h a t t h e t r e a t m e n t o f t h e a c t i v e i n f e c t i o n
d u r i n g p r e g n a n c y p r o t e c t s t h e f e t u s f r o m i n f e c t i o n a n d s o a
c e s a r e a n d e l i v e r y i s n o l o n g e r n e c e s s a r y ( 2 8 - 3 1 ) . T h e s e
s t u d i e s , h o w e v e r , d o n o t r e p r e s e n t l o n g t e r m m o n i t o r i n g o f
t h e c h i l d r e n .
S o m e r e s e a r c h e r s h a v e d e d i c a t e d t h e m s e l v e s t o f i n d i n g
d e f i n i t e p r o o f o f t h e c o n g e n i t a l i n f e c t i o n b y t h e H P V ( 3 2
-3 5 ) . T s e n d e t a l . ( 3 6 ) s t a n d o u t f o r t h e i r s t u d i e s o n v a g i n a l
c e r v i c a l c e l l s a n d t h e p e r i p h e r a l b l o o d o f 5 2 p r e g n a n t w o m e n
( t h i r d q u a r t e r ) a n d b l o o d f r o m t h e c o r d o f t h e r e s p e c t i v e
c o n c e p t u s . T h e y f o u n d H P V 1 6 D N A i n 6 ( 1 1 . 5 % ) s p e c i m e n s
o f v a g i n a l c e r v i c a l c e l l s a n d i n 9 ( 1 7 . 3 % ) o f t h e p e r i p h e r a l
D IA S , E .P .; B A R C E L O S , J .M .P .; F O N S E C A , M .E .F . & B A S S O , N .G .S . - C o n g e n ita l p a p illo m a s a n d p a p illo m a to s e s a s s o c ia te d w ith th e H u m a n P a p illo m a V iru s (H P V ) - re p o rt o n 5 c a s e s
m a te rn a l
b lo o d .
T h e
a n a ly sis
o f th e
c o rd
b lo o d
o f th e
re sp e c tiv e
c o n c e p tu se s
w a s p o sitiv e in 7 .
T h e v u lv a r p a p illo m a to sis
is a n e n tity re c e n tly fo u n d in
a d u lts. Its o rig in a n d c lin ic a l sig n ific a n c e
is still c o n tro v e rsia l
(3 7 -4 1 ). It w a s d e sc rib e d fo r th e first tim e in 1 9 8 2 a n d d e fin e d
a s fin e sc a ly p ro je c tio n s fo u n d in th e v u lv a r v e stib u le (3 8 ,3 9 ).
T h e re a re still d o u b ts c o n c e rn in g th e tru e n a tu re o f th is fre q u e n t
v u lv o sc o p ic
fin d in g ,
w ith a w id e ra n g e o f id e n tific a tio n
o f
th e
v ira l
D N A
(3 7 ,3 8 ,4 1 ).
T h e re
a re
n o re p o rts
o f th e
o c c u rre n c e
o f sim ila r le sio n s in fe tu se s o r n e w b o rn s.
T h e d ia g n o sis o f th e c o n g e n ita l
in fe c tio n is d o n e b y th e
H P V a n d its fe ta l e ffe c ts is a n im p o rta n t c o n trib u tio n
n o t o n ly
fo r th e stu d y
o f b io lo g ic a l
b e h a v io r,
w h ic h
o p e n s
n e w
p e rsp e c tiv e s
fo r re se a rc h , b u t a lso fo r m e d ic a l p ra c tic e w h e re
th e a p p ro a c h to c o n d y lo m a p a tie n ts, p a rtic u la rly
c h ild re n a n d
p re g n a n t w o m e n , sh o u ld b e re v ie w e d .
M A T E R I A L A N D M E T H O D S
T h e
m a c ro
a n d
m ic ro sc o p ic a l
sk in
a lte ra tio n s
o n a
p h a llic p ro je c tio n
o f a m a lfo rm e d
stillb o rn ,
su g g e stiv e
o f a
c y to p a th ic
e ffe c t b y th e H P V , le d u s to re v ie w so m e c a se s in
w h ic h w e a lre a d y h a d o b se rv e d sim ila r a lte ra tio n s in th e g e n ita l
a re a .
T h e re fo re ,
w e p e rfo rm e d
a re v ie w stu d y o f fiv e c a se s,
o n h u m a n
tissu e
in c lu d e d
in p a ra ffin ,
se le c te d
fro m
th e
n e c ro p sie s
o f tw o stillb o rn s
a n d th re e n e o n a te s, a ll o f w h ic h
w e re fe m a le .
O f th e tw o
w h o
w e re m a lfo rm e d ,
o n e h a d
m u ltip le m a lfo rm a tio n s,
a n d a d e c re a se d k id n e y w a s se le c te d
fo r th e p u rp o se
o f re v ie w in g
m o rp h o lo g ic a l
a lte ra tio n s
p re v io u sly c o n sid e re d to b e n e p h ric h y p o p la sia a n d d y sp la sia .
Histopathologic
Exam
A h isto p a th o lo g ic a l
e x a m
w a s p e rfo rm e d
o n th e fiv e
c a se s. S lid e s w e re sta in e d w ith H e m a to x y lin -E o sin ,
u sin g th e
fo llo w in g
c rite ria to e v a lu a te th e sk in w ith g e n ita l le sio n s: a )
h y p e rk e ra to sis,
a c a n th o sis, a n d p a p illo m a to sis;
b ) p e rin u c le a r
h a lo e s
a n d n u c le a r
a b n o rm a litie s;
c ) d e rm a l
in fla m m a to ry
in filtra te .
T h e
id e n tifie d
a b n o rm a litie s
w e re
c la ssifie d
a c c o rd in g
a s lig h t, m o d e ra te , o r a c c e n tu a te d
se v e rity .
H isto lo g ic a l
c u ts in th e c o rtic a l a n d m e d u lla r re g io n s o f
th e re d u c e d k id n e y w e re re v ie w e d fo r th e p u rp o se o f lo o k in g
fo r a b n o rm a litie s
c o m p a tib le
w ith th e in fla m m a to ry
p ro c e ss
th a t c o u ld ju stify
a n a lte ra tio n
in siz e .
Ultramicroscopical
Exam
It w a s p e rfo rm e d
o n th re e o f th e fiv e c a se s (1 ,2 , a n d 4 ).
T h e sa m p le s w e re c o lle c te d
fro m th e g e n ita l le sio n s a n d th e
a lte re d k id n e y , a t th e le v e l o f th e c o rtic a l re g io n (c a se 4 ). T h e
se le c tio n
w a s b a se d o n th e in te n sity
o f
th e a b n o rm a litie s
id e n tifie d
in th e e p id e rm is
a n d in th e n e p h ric
p a re n c h y m a .
P a ra ffin w a s re m o v e d
a n d th e m a te ria l
w a s re p ro c e sse d
fo r
in c lu sio n in re sin (S P U R R ). A fte r th e in c lu sio n , w e p e rfo rm e d
se m i-fin e
a n d u ltra -fin e
c u ts fo r e x a m in a tio n
o n a P h illip s
3 0 I e le c tro n m ic ro sc o p e .
Immunohistochemical
Exam
A n im m u n o h isto c h e m ic a l
e x a m w a s p e rfo rm e d
in th e
fiv e c a se s, w ith "M o n o c lo n a l
P a p illo m a v iru s
H P V
1 6 , L I
M A B 8 8 5 " (C h e m ic o n ).
L e sio n c u ts w ith o u t im m u n e se ru m a n d n o rm a l sk in c u ts
fro m th e n e w b o rn in w h ic h im m u n e se ru m w a s a p p lie d w e re
u se d a s n e g a tiv e re fe re n c e s. M a te ria l o b ta in e d fro m a u te rin e
c e rv ix in fe c te d b y H P V w a s u se d a s a p o sitiv e re fe re n c e .
R E S U L T S
T h e
c a se s
stu d ie d
p re se n te d ,
a m o n g
o th e r
th in g s,
e x te rn a l g e n ita l p a p illo m a to sis
le sio n s (fig u re
I). T h e m a in
c lin ic a l d a ta o f th e m o th e rs
c a n b e se e n o n ta b le
I. In th e
m a te ria l se le c te d
fo r th e stu d y , w e id e n tifie d
th e fo llo w in g
a sp e c ts (ta b le 2 ):
Optical Microscopy
C a se 1 : P a p illo m a
w ith e p id e rm is p re se n tin g
m o d e ra te
h y p e rk e ra to sis,
a c a n th o sis,
a n d p a p illo m a to sis
a n d c e ll w ith
F I G U R E 1 - M a c r o s c o p ic A s p e c t o f t h e V u lv a r L e s io n s : 1 - C a s e 1 : p o ly p - lik e f o r m a t io n in t h e v a g in a l in t r o it u s . 2 - C a s e 2 : s m a ll p o ly p in v a g in a l in t r o it u s ( ) a n d v u lv a l
p e r in e u m d e r m is w it h p a p illo m a t o s is ( * ) . 3 - C a s e 3 : d is c r e t e v u lv a r p a p illo m a t o s is .
4 - C a s e 4 : v u lv a p a p illo m a s ( e ) , c h e s t ( b ) , a n d a r e o la ( c ) , h a r e lip ( a ) , b i- c o r n if ic a t e d u t e r u s ( d ) a n d r e n a l h y p o p la s ia ( f ) .
5 - C a s e 5 : G a s t r o c h is is ( a ) w it h g e n it a lia a b s e n t ( b ) a n d p h a llic p r o je c t io n
O .
C N = C a s e n u m b e r / P /D = P r e g n a n c ie s /D e liv e r ie s / P P = P r e v io u s p r e g n a n c ie s / P B = P r e - d e liv e r y L = L a b o r / C = C o n c e p tu s / N = N e c r o p s y / P I= P la c e n ta / S b = S tillb o r n
P S H D = P r e g n a n c y S p e c ific H y p e r te n s io n D is e a s e / N I= N o n s p e c ific in fla m m a tio n A P = A s c e n d in g p la c e n titis
I
N S p = N o s p e c ia l fe a tu r e s / A H = A r te r y h y p e r te n s io n / F = F e tu s N N = N e o n a te d e a d / N o l= N o in fla m m a tio n / P V = P r o life r a tin g v ilo s itis / D M = D ia b e te s m e llitu m P M = P r e m a tu r e / Iv = ln te r v iio s itis / M F = M a lfo r m e d / B I= B a c te r ia l in fe c tio n / N E = N o t e x a m in e dImmunohistochemical
Electron Microscopy
T he cases
1,2,4,
and 5 presented epiderm icim m unopositivity for anti-H P V 16 L l.
T he brow nish granulations w ere identified,
predom inantly in the cytoplasm ofthe cells of the interm ediate
and superficial layers. N uclear m arking, though dispersed,
w as present. C ase three show ed rare brow nish granulations,
and w as considered to be negative.
PI
A P
NE
P V ?
Iv
A P
N
N I
N o l
N o l
B I
N o l C
S b
NN
N N
N N M F
S b M F
thickened capsule w as
observed on the cuts from the
left kidney, peri-glom erular
and peri-tubular fibrosis, w ith
m ononuclear inflam m atory
infiltrate and few neutrophils.
T hese abnorm alities w ould
suggest an aggression to the
nephric parenchym a,
follow ed by fibrosis and a
reduction in the nephric size.
C ase 5: Instead of a w ell
defined genitalia, the fetus
had a phallic projection,
coated w ith squam ous m ucosa
and a cistic form ation covered
w ith squam ous epitheliocyte,
containing keratin.
W e identified, on the
squam ous epithelium
hyperkeratosis, irregular
acanthosis and m oderate
papillom atosis (figure 2.5 A ).
W e noticed num erous cells
w ith P N H , nuclei portraying
an increase in size, w ith light hyperchrom asia, oval, "flattened"
in som e areas, fusiform or binucleated (figure 2.5 B ). In the
subjacent conjunctive tissue the vessels presented ectasis and,
in som e areas, w ere involved by m ononuclear inflam m atory
cells.
T he ultrafine cuts of the skin in cases 1,2, and 4 show ed,
in the epiderm ic cells, viral precursors, 27 nm in diam eter
located in the nucleus; and w hole viral particles, w ith an
average diam eter of 50 nm located in the cytoplasm and
nucleus. In the tissue of the kidney (case four), viral particles
sim ilar to those of the skin w ere found located in the nucleus
and cytoplasm of the tubular epithelial cells (figure three),
different from the dense fibrillar and fibroblast population,
w here w e did not see viral particles.
T a b le 1
M a in d a ta r e g a r d in g th e c o n c e p tu s e s e x a m in e d b y n e c r o p s y .
CN
Age
P/O
PP
PB
L
3 7 V IIN I V I m o la r P S H O m e c o n iu m a n d c irc u la r
2
?
V /IV N S p A H g e m e la ry F 1 -N S pF 2 -c ro s s e d
3 3 1 IV /III O M g e m e la ry F 1 -P M
F 2 -P M 4 ' 3 5 II/I N S p s to p in g ro w th d iffic u lt
a t 6 m o .
5
?
?
?
c o n ta c t w / d iffic u ltru b e lla
perinuclear haloes (P N H ) in the m ore superficial layers
(figure 2.1).
T he nuclei w ere larger than norm al for the superficial
layer. T hey w ere oval or w ith a "flattened" aspect, w ell defined,
occasionally fusiform and rarely binuclear. T he superficial
derm is show ed ectasis and slight m ononuclear inflam m atory
infiltrate, predom inantly peri-vascular.
C ase 2: M oderate cutaneous hyperkeratoses, acanthosis,
and accentuated papillom atosis, epithelial hyperplasia w ith
num erous cells w ith P N H , particularly in the interm ediary
and superficial layers, w ith nuclei portraying a "flattened"
aspect, m ultilobed or fusiform (figure 2.2). D erm is w ith
congested vessels and surrounded by a m oderate quantity of
m ononucleated inflam m atory cells.
C ase 3: V aginal epithelium w ith hyperplasia and
cytoplasm atic vacuoles, due to glycogenic deposit. T he skin
presented slight and m oderate hyperkeratosis, m oderate and
focal acanthosis, light papillom atosis and areas w ith P N H and
oval nuclei, som etim es "flattened" or fusiform . In the derm is,
vascular ectasis and areas of light m ononuclear inflam m atory
infiltrate (figure 2.3)
C ase 4: E piderm is of the polypoid lesion w ith
hyperkeratosis and m oderate acanthosis, accentuated
papillom atosis and areas of cells w ith P N H and oval nuclei,
colored in excess, fusiform or "flattened"; found in the
interm ediary and superficial layers (figure 2.4). T he presence
of m oderate derm al inflam m atory infiltrate w as noted, form ed
by m ononuclear leukocytes, predom inately perivascular. A
D IA S , E .P .; B A R C E L O S , J .M .P .; F O N S E C A , M .E .F . & B A S S O , N .G .S . - C o n g e n ita l p a p illo m a s a n d p a p illo m a to s e s a s s o c ia te d w ith th e H u m a n P a p illo m a V ir u s ( H P V ) - r e p o r t o n 5 c a s e s
E M
V P V P N S V P N S Ip
Ip IH C
Ip
Ip
possible
to identify the viral particles
and their characteristics,
and the approxim ate
size of 50 nm support
the com patibility
w ith the H P V (47-50).
In case 4, the presence
of peri tubular,
periglom erular
and
interstitial
fibrosis
associated
to an
inflam m atory
infiltrate,
represent
abnorm alities
that justify
the nephric decrease
in size. T he identification
of viral particles
in tubular
cells confirm s
the association
of the abnorm alities
to the H P V , how ever,
it does not m ake
possible
an etiologic
association,
since the H P V
m ay have
infected
the abnorm al
nephric
tissue T his raises som e questions,
such as, the path of
infection.
In this case
w e could
not prove
that the viruses
infected
the
kidney
by hem atogenous
spread,
since
the
am niotic
liquid
could
have
been
infected
via
ascendens.
S tudies for viral identification
in other m alform ations
or tissues
reachable
only hem atogenically
are required.
T he studies
that use the IH Q
techniques
to reveal
the
presence
of H P V
antigen,
indicate
m arked
nuclei
are
a
standard
of positivity
(50-54).
A ll
these
studies
w ere
perform ed
on the lesions
of adult patients,
and though
there
are technical
variations
and variations
and in the results,
the
expressive
nuclear
m arking
alw ays
being present.
P adayache
(53), in 1987, published
the results
of their
studies
on oral
papillom as.
It describes,
along
w ith
positive
and
negative
groups,
a group
w ith 9% of doubtful
cases,
w ith
cells
w ith
cytoplasm atic
im m unopositivity
exclusively
or in the nucleus
and cytoplasm .
T he
identification
of discontinued
areas
of
the nuclear m em brane,
though the possibility
of artifact should
be considered,
and
the
com plete
particles
found
in the
cytoplasm
in the cases
of congenital
vulvar
lesions,
m ay
explain
the cytoplasm atic
m arking
by im m unohistochem ical
(lH Q ), justifying
the scarce
nuclear
m arking.
In the reference
groups,
the epiderm ic
m arking
w as expressive
only
in case
five, w hich w as repeated
together
w ith the negative
references,
im m unopositivity
w as
show n
only
in the
lesion
cut
w ith
im m une
serum . T he positive
reference
that w as used show ed
the expected
nuclear
m arking.
C onsidering
that the studies
of lesions
w ere done on stillborns
and
dead
neonates,
it can
be
affi rm ed
that
the
infection
happened
intra-uterus,
though
the
hem atologic
or ascendant
spread
could
be discussed.
T he studies about condylom a
show
that
the
evolution
is
unpredictable:
som e
cases
resolve
spontaneously,
others that
recur, and others
persist
and can
be associated
to the developm ent
of carcinom as
(28-30,43,55).
T he
factors
involved
in
the
determ ination
of evolution
by the
H P V are still not com pletely
clear.
A nyw ay,
the
H P V
type,
the
IU M n M /M n U M n M /M n U M n N u
+
++
+
+++
+ O p tic a l M ic ro s c o p y
A c P p P N H
M M + +
S
S
+++
M L +
M
S
+++
M M + +
H k
M
M
L M M M C
P
P /P p
P p
P
P
T a b le 2
M a in d a ta fro m m a c ro s c o p ic , h is to p a th o lo g y , im m u n o h is to c h e m ic a l a n d u ltra m ic ro s c o p ic a l e v a lu a tio n o f th e v u lv a r le s io n s .
C S = C a s e / M C = M a c ro s c o p ic c o n c lu s io n s / P = P a p illo m a / H k = H y p e rk e ra to s is / A c = A c a n th o s is P p = P a p illo m a to s is / P N H = P e rin u c ie a r h a lo / L = L ig h t / M = M o d e ra te / S = S e v e re
N u = N u c le a r a lte ra tio n s / 1 = ln fla m m a tio n / M n = M o n o n u c ie a r / IH C = lm m u n o h is to c h e m ic a l E M = E le c tro n m ic ro s c o p y / + = D e g re e / N S = N o t s e le c te d c a s e / V P = V iru s p a rtic le s Ip = lm m u n o p o s itiv ity
CS
1
2 3
4
5
T he genital
w orts are lesions
that have been recognized
since
antiguity
and referred
to by m any
G reek
and R om an
w riters
(42). U ntil
1954 the m echanism
of transm ission
w as
still not clear, the viral etiology
w as only established
in 196842
and w as further
investigated
only after becam e
associated
to
the vul val carcinom a
(43). T he potential
of fetal infection
of
som e
viruses
is w ell know n.
T he possibility
of H P V
being
one of these viruses
has been described
in the last few years
(32-36).
In our report
of the fi ve cases of congenital
papillom as
and papillom atosis,
identified
in stillborns
and new ly
borns
dead after a short period
of tim e, during
the initial necropsy
the possibility
of a viral lesion
w as not considered,
except
in
the last case, in w hich
a necroscopy
exam
w as done in 1991.
In this w ay, it becam e
a triggering
factor for the re-evaluation
of the other cases.
T he histopathological
aspects
observed
in the lesions
that w ere studied,
correspond
and are classically
described
as
being associated
to the injection
by the H P V . In all the cases
w e observed
epiderm ic
abnorm alities,
such as, hyperkeratosis,
acanthosis,
papillom atoses
and perinuclear
haloes
sim ilar
to
the
K oylocitosis
(44-46).
In the
lesions
w e studied,
the
vacuolated
cells
show ed
aspects
very
sim ilar
to the ones
described
in the
literature,
w ith
am ple
and
w ell-defined
perinuclear
haloes,
involving
various
aspects
of nuclei:
w ith
a single
or double
nucleus,
increased
in size, oval, fusiform ,
w ith condensed
and granulated
chrom atin,
w ith central clear
areas and peripheral
chrom atin.
In
all
of
the
vulval
lesions
subm itted
to
the
ultram icroscopy
study, w e identified
viral particles.
In spite
of the artifacts
consequent
to the reprocessing
of m aterial
included
in paraffin.
S om e authors
have dem onstrated
that its
D IS C U S S IO N
FIGURE 2 - H isto p a th o lo g ica l A sp e cts o f th e V u lva r L e sio n s: 1 - C a se 1 ; 2 - C a se 2 ; 3 - C a se 3 ; 4 - C a se 4 ; 5 - C a se 5 ; A I ca se s sh o w , in d iffe re n t d e g re e s: h yp e rke ra to sis, a ca n th o sis; p e ri-n u cle a r h a lo s a sso cia te d to irre g u la r fo rm a tio n s; n u cle a r h yp e rch ro m a tism a n d b in u cle a tio n
O .
i m m u n o l o g i c a l s t a t u s o f t h e h o s t , a s w e l l a s g e n e t i c f a c t o r s ,
a r e i n v o l v e d ( 5 6 ) . C o n s i d e r i n g s t i l l , t h a t p r e g n a n c y i s a p e r i o d
p a r t i c u l a r l y s u s c e p t i b l e t o t h e a p p e a r a n c e o f c o n d y l o m a t a
a c u m i n a t a a n d c e r v i c a l l e s i o n s , i t i s p r o b a b l e t h a t t h e H P V
t y p e , t h e i n t e n s i t y o f t h e l e s i o n , t h e t i m e o f e v o l u t i o n , a n d t h e
s t a g e o f p r e g n a n c y i n w h i c h t h e m a t e r n a l i n f e c t i o n o c c u r s ,
m a y b e s o m e o f t h e f a c t o r s i n v o l v e d i n t h e o c c u r r e n c e o f f e t a l
i n f e c t i o n a n d i n t h e d e t e r m i n a t i o n o f i t s s e v e r i t y a n d
c o n s e q u e n c e s .
R e s u l t i n g m o r p h o l o g i c a l a l t e r a t i o n s o f t h e c o n g e n i t a l
i n f e c t i o n m a y n o t b e p r e s e n t a t b i r t h , s i n c e a 6 - 8 m o n t h
i n c u b a t i o n p e r i o d h a s t o b e t a k e n i n t o a c c o u n t . T h e l e s i o n s
i d e n t i f i e d m o n t h s a f t e r b i r t h , r e p o r t e d b y s o m e a u t h o r s
( 5 ,1 5 ,1 6 ) , c a n b e t h e e x p r e s s i o n o f a n i n t r a - u t e r i n e i n f e c t i o n .
I n 1 9 7 4 , B a r c e l l o s e t a l . ( 5 7 ) , a f t e r s t u d y i n g c y t o
-h i s t o l o g i c a l l y 1 9 5 m a c r o s c o p i c a l l y n o r m a l u t e r i n e c e r v i x e s
o f i n f a n t s , n e w b o r n s , a n d f e t u s e s , i d e n t i f i e d d y s p l a s t i c c e l l u l a r
a t y p i a s i n t h e s q u a m o u s m u c o s a i n s o m e c a s e s a n d i n q u i r e d ,
" W h y w o u l d t h e s e p a t h o l o g i c a l a b n o r m a l i t i e s e x i s t i n a n o r m a l
f e t u s , n e w b o r n , a n d i n f a n t s ? " . T h e r e c e n t e v i d e n c e s o f
c o n g e n i t a l i n f e c t i o n b y t h e H P V i n d i c a t e t h e p o s s i b i l i t y t h a t
t h e d y s p l a s t i c a b n o r m a l i t i e s c o r r e s p o n d t o t h e v i r a l i n f e c t i o n .
T h e i n t r a - u t e r i n e f e t u s i n f e c t i o n b y t h e H P V r a i s e s s o m e
q u e s t i o n s . I t i s k n o w n t h a t m a n y w o m e n p r e s e n t t h e l a t e n t
i n f e c t i o n ( 3 ,5 8 - 6 0 ) , t h a t t h e r e i s a r e l a t i o n b e t w e e n t h e H P V
t y p e a n d t h e a n a t o m i c a l s i t e o f t h e l e s i o n s ( 6 1 ,6 2 ) a n d t h e
e v o l u t i o n t h a t s e e m s t o v a r y a c c o r d i n g t o t h e h o s t 's p a r t i c u l a r
c h a r a c t e r i s t i c s ( 6 2 ,6 3 ) . W o u l d t h e s e a s p e c t s b e v a l i d f o r a
f e t u s i n f e c t i o n ? I s t h e r e a m o m e n t i n w h i c h t h e f e t u s i s m o r e
s u s c e p t i b l e t o i n f e c t i o n ? W o u l d a m o r e e f f i c i e n t f e t u s
i m m u n o l o g i c a l r e s p o n s e c a u s e t h e l e s i o n s n o t t o a p p e a r ? C a n
t h e i n f e c t i o n b y t h e H P V b e a c a u s e o f s p o n t a n e o u s a b o r t i o n ?
I n t h e c o n g e n i t a l i n f e c t i o n b y t h e H P V , t h e c y t o p a t h i c
c o n s e q u e n c e s s h o u l d , s i m i l i a r l y t o o t h e r b o d i l y a r e a s , v a r y
w i t h t h e t y p e o f v i r u s a n d p r e g n a n t w o m a n 's i m m u n o l o g i c a l
c o n d i t i o n s . T h u s , a n a m p l e s p e c t r u m o f p o s s i b i l i t i e s i s o p e n e d
t h a t c a n v a r y f r o m n o n a p p a r e n t i n f e c t i o n t o s e v e r e
a b n o r m a l i t i e s i n t h e f e t a l m o r p h o g e n e s i s a n d i n f l u e n c e o n t h e
m o r b i d i t y a n d d e a t h .
T h e r e f o r e , e v i d e n c e s a r e a d d i n g u p t o s h o w t h a t t h e
H P V , b e s i d e s b e i n g s p e c i f i c t o h u m a n s , i n f e c t i n g t h e s k i n a n d
m u c o s a l m e m b r a n e s , b e i n g s e x u a l l y t r a n s m i t t a b l e , i n f e c t i n g
f e t u s e s a t t h e m o m e n t o f b i r t h , a n d b e i n g t r a n s m i t t e d b y n o n
-s e x u a l c o n t a c t , p r o b a b l y a t s o m e m o m e n t o f i t s b i o l o g i c a l
c y c l e d i s s e m i n a t e s i t s e l f v i a a s c e n d a n t s a n d / o r
h e m a t o g e n i c a l l y a n d , i n p r e g n a n t w o m e n , c r o s s e s t h e p l a c e n t a l
b a r r i e r a n d c a u s e s f e t a l i n f e c t i o n .
F o r t h e s a m e r e a s o n t h e l e s i o n s h a v e n o t d r a w n a t t e n t i o n
b e f o r e , w e b e l i e v e t h a t o t h e r s i m i l a r s i t u a t i o n s h a v e o c c u r r e d
a n d t h a t t h e i n c i d e n c e o f g e n i t a l p a p i l l o m a o r t h e i n f e c t i o n i n
o t h e r a r e a s o f t h e s k i n , i s g r e a t e r t h a n w h a t i s d e s c r i b e d i n
l i t e r a t u r e . I t i s p o s s i b l e t h a t a s o b s t e t r i c i a n s , p e d i a t r i c i a n s ,
a n d p a t h o l o g i s t s s t a r t g i v i n g m o r e a t t e n t i o n t o t h e f e t u s e s '
g e n i t a l i a a n d s k i n , t h e p a p i l l o m a s a n d t h e p a p i l l o m a t o s e s w i l l
b e m o r e a p p a r e n t .
T h e h i s t o p a t h o l o g i c a l a b n o r m a l i t i e s c l a s s i c a l l y
d e s c r i b e d a s b e i n g c o m p a t i b l e w i t h t h e i n f e c t i o n b y t h e H P V
i n a d u l t s , a r e p r e s e n t i n c o n g e n i t a l p a p i l l o m a s a n d
p a p i l l o m a t o s e s .
FIGURE 3 - Im m u n o -H isto ch e m ica l A sp e cts a n d U ltra stru ctu re N u cle a r a n d C yto p la sm ic Im m u n o p o sitivity:
1 - C a se 2 ; 2 - C a se 4
3 - D isru p tio n o f th e n u cle a r m e m b ra n e
0
a n d p e rin u cle a r cle a ra n ce (ca se 4 - 1 5 ,0 0 0 x)4 - R e n a l tu b u la r ce ll (ca se 4 ):
A . vira l p a rticle s o f 5 0 n m (3 0 ,0 0 0 x) B . p a rticle s e n la rg e m e n t (8 1 ,0 0 0 x)
D IA S , E .P .; B A R C E L O S , J.M .P .; F O N S E C A , M .E .F . & B A S S O , N .G .S . - C o n g e n ita l p a p illo m a s a n d p a p illo m a to se s a sso cia te d w ith th e H u m a n P a p illo m a V iru s (H P V ) - re p o rt o n 5 ca se s
The im m unopositivity
for the L I protein of the H PV
capsid in the nucleus and cytoplasm of the epiderm ic cells of
4 of the 5 lesions studied and the identification of nuclear and
cytoplasm atic viral particles, m easuring approxim ately 50 nm ,
in the epiderm ic cells of three lesions, confirm the association
betw een the H PV and the lesions studied. H ow ever, only m ore
detailed studies w ith a greater num ber of cases can definitely
confirm the involvem ent of the H PV in the etiology of these
lesions.
RESUMO
In tro d u ~ a o : O s a u to re s a p re s e n ta m u m e s tu d o d e c in c o c a s o s d e p a p ilo m a s e p a p ilo m a to s e s v u lv a re s c o n g e n ita s e m n e o e n a ti-m o rto s . M a te ria l e M tH o d o s : 0 m a te ria l u tiliz a d o fo i p ro v e n ie n te d e c in c o n e c r6 p s ia s . A a v a lia c ;:a o h is to p a to l6 g ic a m o s tro u a s p e c to s s u g e s tiv o s d e in fe c c ;:a o p e !o P a ilo m a v iru s h u m a n o (H P V ). A m ic ro s c o p ia e le tro n ic a d e tre s d o s c a s o s id e n tific o u p a rtic u la s v ir6 tic a s n u c le a re s e c ito p la s m a tic a s v a ria n d o d e40 a60 n m , c o m p a tiv e is c o m H P V . R e s u lta d o s : 0 e s tu d o im u n o -h is to q u im ic o d e s ta s le s 6 e s d e m o n s tro u ir:n u n o p o s itiv id a d e c ito p la s m a tic a e n u c le a r. C o n c lu s a o : O s a u to re s c o n c lu ira m q u e a p re s e n c ;:ad e p a rtic u la s v ir6 tic a s .s o m a d a a im u n o p o s itiv id a d e e m c e lu la s e s c a m o s a s , s a o e v id e n c ia s d o p ro v a v e l e n v o lv im e n to e tio l6 g ic o d o H P V n e s ta s le s 6 e s .
REFERENCES
I. O RTH , G . et alii. The hum an papillom aviruses. Bull. Cancer, 65: 151-164,1978.
2. O STRO W , R.S. & FA RA S, A J. The m olecular biology of H um an papillom aviroses and the pathogenesis of genital
papillom as and neoplasm a. Cancer and M etastasis Review , 6: 383-395, 1987.
3. SY RJA N EN , K J. Epidem iology of H um an papillom avirus
(H PV ) infection and their associations w ith genital squam ous cell cancer. A PM IS, 97: 957-970, 1989.
4. D IA S, E.P Papillom avirus hum ano: aspectos biol6gicos, clfnicos
e m orfol6gicos. JM B, 64 (6): 206-17,1993.
5. D E JO N G , A .R., W EISS, J.e. & BREN T, R.L. Condylom a acum inata in children. A m . J. D is. Child., 136 (8): 704-706, A ugust, 1982.
6. TA N G , C-k; SH ERM ETA , D & W O O D , C Congenital condylom a acum inata. A m . J. O bst. & G inecoI., 15:912-913, 1978.
7. STU M PF, PG . Increasing occurrence of condylom ata acum in& ta in prem enarchal children. O bst. & G inecoI., 56 (2): 262-264, 1980.
8. JO N ES, J.G . Sexual abuse of children. Current concepts. A m . J. D is. Child., 136 (2): 142-146, 1982.
9. D E JO N G , A .R. Sexually transm itted diseases in children. A m . Fam . Physician., 30 (1): 185-193, 1984.
10. STRIN G EL, G ., M ERCER, S. & CO RSIN I, L Condylom a acum inata in children. J. Pediatri. Surg., 20 (5) : 499 - 501,
1985.
II. RO CK , B. et alii. G enital tract papillom avirus infection in children. A rch. D erm atoI. 122 (10) :1129-1132, O ct, 1986. 12. BEN D ER, M .E. N ew concepts of condylom a acum inata in
children. A rch. D erm atoI., 122 (10): 1121-1124, O ct, 1986.
13. V A LLEJO S, H . et alii. Characterization of H um an Papillom a V irus types in condylom ata acum inata in children by in situ hybridization. Lab. Invest., 56 (6): 611-615,1987.
14. STEIN BERG , B.M . Papillom avirus. Effects upon m other and child. A nn. N . Y . A cad. Sci., 549 (12): 118-128, 1988. IS. SIN G H , K .G ., BA JA J, A .K . & SH A PM A , R. Perianal
condylom a acum inatum in an infant. Int.
J.
D erm atoI., 27 (3): 181-182, 1988.16. G IBSO N , P.E., G A RD N ER, S.D . & BEST,
S.l.
H um an papillom avirus types in anogenital w arts of children ..T.
M ed. V iroI., 30 (2): 142-145, Feb, 1990.17. BO Y D , A .S. Condylom ata acum inata in the pediatric population. A m . J. D is. Child., 144 (7): 817-824, 1990.
18. N U O V O , G J. et alii. H um an papillom avirus segregation patterns in genital and nongenital w arts in prepuberal children and adults. A m .
J.
CIin. PathoI., 95: 467-474, 1991.19. CRA IG H ILL, M .e. H um an Papillom avirus Infection in Children
and A dolescents. Sem . Pediatr. Infect. D is., 4 (2): 85-93, 1993. 20. CH A CK O , M .R. & TA BER, L.H . Epidem iology of Sexually
transm itted D iseases in Children and A dolescents in the U nited States. Sem . Pediatr. Infect. D is., 4 (2): 71-76, 1993.
21. H O RD IN G , U . et alii. Prevalence of H um an papillom avirus types 11, 16 and 18 in cervical sw abs. A study of 1362 pregnant w om en. Eur. J. O bst. et G ynecoI. Reprod. BioI., 35 (2-3): 192-8,1990.
22. BEU RET, T., SA D O U L, G ., FA RL, A ., IO N ESCO , M . & D E BRU X , J. Estude epidem iologique com parative entre 120 patientes atteintes de lesion condylom ateuse et 120 patientes tem oins. J. G ynecoI. O bstet. BioI. Reprod. (Paris), 16 (5): 555-564, 1987.
23. G A RRY , R. & JO N ES, R. Relationship betw een cervical condylom ata, pregnancy and subclinical papillom avirus infection. J. Reprod. M ed., 30 (5): 395-399, 1985.
24. RA Y M O N D , F.R. &TH O M A S, RJ. Condylom a acum inatum in pregnancy .
.T.
A m . O steopath. A ssoc., 82 (10): 774-778, 1983.2 5 . H A L L D E N , C .
&
M A JM U D A R , B . T h e re la tio n sh ip b e tw e e nju v e n il la ry n g e a l p a p illo m a to sis a n d m a te rn a l c o n d y lo m a ta
a c u m in a ta .
J.
R e p ro d . M e d ., 3 1 (9 ): 8 0 4 -8 0 7 , 1 9 8 6 .2 6 . K JE R , J.J., E L D O N , K .
&
D R E IS L E R , A . M a te rn a lc o n d y lo m a ta a n d ju v e n illa ry n g e a l p a p illo m a s in th e ir c h ild re n .
Z e n tra Ib l. G y n a k o l., 1 1 0 (2 ): 1 0 7 -1 1 0 , 1 9 8 8 .
2 7 . F L E T C H E R , J.L Jr. P e rin a ta l tra n sm issio n o f H u m a n
p a p illo m a v iru s. A m . F a m . P h y sic ia n ., 4 3 (1 ): 1 4 3 -8 , 1 9 9 1 .
2 8 . C A L K IN S , J. W ., M A S T E R S O N , B .1 ., M A G R IN A , J.F .
&
C A P E N , c .v . M a n a g e m e n t o f c o n d y lo m a ta a c u m in a ta w ith th e
c a rb o n d io x id e la se r. O b ste t. G y n e c o l., 5 9 (1 ): 1 0 5 -1 0 8 , 1 9 8 2 .
2 9 . B E R G M A N , A ., M A T S U N A G A , 1 .
&
B H A T IA , N .N . C e rv ic a lc ry o th e ra p y fo r c o n d y lo m a ta a c u m in a ta d u rin g p re g n a n c y .
O b ste t. G y n e c o l., 6 9 (1 ): 4 7 -5 0 , 1 9 8 7 .
3 0 . M A T S U N A G A , J., B E R G M A N , A .
&
B H A T IA , N .N G e n ita lc o n d y lo m a ta a c u m in a ta in p re g n a n c y : e ffe c tiv e n e ss, sa fe ty a n d
p re g n a n c y o u tc o m e fo llo w in g c ry o th e ra p y . B r . .1 . O b ste t.
G y n e c o l., 9 4 (2 ): 1 6 8 -1 7 2 , 1 9 8 7 .
3 1 . A U D R A , P . [T h e m a n a g e m e n t o f p re g n a n t w o m e n p re se n tin g
w ith g e n ita l H P V in fe c tio n s]. R e v . F r. G y n e c o l. O b ste t., 8 5
(1 0 ): 5 6 1 -3 ,1 9 9 0 .
3 2 . R O G O , K .O .
&
N Y A N S E R A , P .N . C o n g e n ita l c o n d y lo m a taa c u m in a ta w ith m e c o n iu m sta in in g o f a m n io tic flu id a n d fe ta l
h y d ro c e p h a lu s: c a se re p o rt. E a st. A fr. M e d . .1 ., 6 6 (6 ): 4 1 1
-4 1 3 , Ju n , 1 9 8 9 .
3 3 . P A T S N E R , B ., B A K E R , D .A .
&
JA M E S , W .O .Jr. H u m a np a p illo m a v iru s g e n ita l tra c t in fe c tio n s d u rin g p re g n a n c y . C lin .
O b ste t. a n d G y n e c o l., 3 3 (2 ): 2 5 8 -2 6 7 , 1 9 9 0 .
3 4 . R O M A N , A .
&
F IF E K . H u m a n p a p illo m a v iru s D N A a sso c ia te dw ith fo re sk in s o f n o rm a l n e w b o rn s. L . In fe c t. D is., 1 5 3 : 8 5 5 ,
1 9 8 6 .
3 5 . S E D L A C E K , T .v ., L IN D H E IM , S . E d e r, C . e t a lii. M e c h a n ism
fo r h u m a n p a p illo m a v iru s tra n sm issio n a t b irth . A m . .1 . O b ste t.
G y n e c o l., 1 6 1 : 5 5 , 1 9 8 9 .
3 6 . T S E N G , C 1 . e t a lii. - P o ssib le tra n sp la c e n ta l tra n sm issio n o f
h u m a n p a p illo m a v iru se s. A m . .1 . O b ste t. G y n e c o l., 1 6 6 : 3 5 -4 0 , 1 9 9 2 .
3 7 . B E R G E R O N , C ., F E R E N C Z Y , A ., R IC H A R T , R .M .
&
G U R A L N IC K . M . M ic ro p a p illo m a to sis L a b ia lis a p p e a rs
u n re la te d to H u m a n p a p illo m a v iru s. O b ste t. G y n e c o l., 7 6 (2 ):
2 8 1 -2 8 6 , 1 9 9 0 .
3 8 . C O S T A , S . e t a lii. Is v e stib u la r p a p illo m a to sis a sso c ia te d w ith
H u m a n p a p illo m a v iru s? .1 . M e d . V iro l., 3 5 : 7 -1 3 ,1 9 9 1 .
3 9 . M c K A Y , M . V u lv ite a n d v u lv o v a g in itis: c u ta n e o u s
c o n sid e ra tio n s. A m . .1 . O b ste t. G y n e c o l., 1 6 5 (4 ): 1 1 7 6
-1 -1 8 2 ,-1 9 9 -1 .
4 0 . M A R IN O F F , S . C .
&
T U R N E R , M .L .C . V u lv a r v e stib u litissy n d ro m e : a n o v e rv ie w . A m . .1 . O b ste t. G y n e c o l., 1 6 5 (4 ): 1 2 2 8
-1 2 3 3 ,-1 9 9 -1 .
4 1 . W IL K IN S O N , E .J. e t a lii. V u lv a r v e stib u litis is ra re ly a sso c ia te d
w ith h u m a n p a p illo m a v iru s in fe c tio n ty p e s 6 , II, 1 6 o r 1 8 . In t.
.1 . G y n e c o l. P a th o l., 1 2 (4 ): 3 4 4 -9 , 1 9 9 3 .
4 2 . O R IE L , 1 .0 . N a tu ra l h isto ry o f g e n ita l w a rts. B rit. .1 . V e n e r. D is., 4 7 : 1 -1 3 , 1 9 7 1 .
4 3 . B A R O U R ,
S.,
L IN D E L V F , B .&
E K L U N D , G . C o n d y lo m a taa c u m in a ta a n d risk o f c a n c e r: a n e p id e m io lo g ic a l stu d y . B M .1 ,
3 0 3 (1 0 ): 3 4 1 -3 4 4 , 1 9 9 1 .
4 4 . A Y R E , J .R . T h e v a g in a l sm e a r. "P re c a n c e r" c e ll stu d ie s u sin g a
m o d ifie d te c h n iq u e . A m . .1 . O b ste t. G y n e c o l., 5 8 : 1 2 0 5 -1 2 1 9 ,
1 9 4 9 .
4 5 . R E A G A N , J.W ., H IC K S , D .J.
&
S C O T Y , R .B . A ty p ic a lh y p e rp la sia o f u te rin e c e rv ix . C a n c e r, 8 : 4 2 -5 3 , 1 9 5 5 .
4 6 . K O S S , L .G .
&
D U R F E E , G .R > U n u su a l p a tte rn s o f sq u a m o u se p ith e liu m o f th e u te rin e c e rv ix : c y to lo g ic a n d p a th o lo g ic stu d y
o f k o ilo c y to tic a ty p ia . A n n . N Y . A c a d . S c i., 6 3 : 1 2 4 5 -1 2 6 1 ,
1 9 5 6 .
4 7 . O R IE L , J.D .
&
A L M E ID A , J.D . D e m o n stra tio n o f v iru s p a rtic le sin h u m a n g e n ita l w a rts. B rit .
.T.
V e n e r. D is., 4 6 : 3 7 -4 2 , 1 9 7 0 . 4 8 . G O N Z A L E Z -A N G U L O , A ., C H A V E Z , I.R .&
C A S T A N E D A ,M . A re lia b le m e th o d fo r e le c tro n m ic ro sc o p ic e x a m in a tio n o f
sp e c ific a re a s fro m p a ra ffin -e m b e d d e d tissu e m o u n te d o n g la ss
slid e s. A m . S o c . C lin . P a th o l., 7 0 (4 ): 6 9 7 -6 9 9 , 1 9 7 8 .
4 9 . K A D IS H , A .S ., B U R K , R .D ., K R E S S , Y ., C A L D E R S .
&
R O M N E Y , S . H u m a n P a p illo m a v iru se s o f d iffe re n t ty p e s in
p re c a n c e ro u s le sio n s o f th e u te rin e c e rv ix : H isto lo g ic ,
Im m u n o c y to c h e m ic a l a n d u ltra stu c tu ra l stu d ie s. H u m . P a th o l.,
1 7 : 3 8 4 -3 9 2 , 1 9 8 6 .
5 0 . O A S H I, M .
&
O G IY A M A Y . E le c tro n m ic ro sc o p ic e x a m in a tio no f c u ta n e o u s le sio n s b y th e q u ic k re m b e d d in g m e th o d fro m
p a ra ffin -e m b e d d e d b lo c k s . .1 . C u ta n . P a th o l. 2 1 : 2 3 9 -2 4 6 , 1 9 9 4 .
5 1 . W O O D R U F F , J.D . e t a lii. Im m u n o lo g ic id e n tific a tio n o f
p a p illo m a v iru s a n tig e n in c o n d y lo m a tissu e s fro m th e fe m a le
g e n ita l tra c t. O b ste t. G y n e c o l., 5 6 (6 ): 7 2 7 -7 3 2 , 1 9 8 0 .
5 2 . G O E S JU N IO R , J.S . e t a lii: P re se n ~ a d e a n tfg e n o s d e
p a p ilo m a v fru s e m le so e s p re -m a lig n a s d a c e rv ic e u te rin a n o
B ra sil. U rn e stu d o im u n o -h isto q u fm ic o d e 9 0 c a so s. R e v . B ra s.
G in e c . O b ste tr., m a io / ju n h o : 1 2 8 -1 3 3 , 1 9 8 3 .
5 3 . P A D A Y A C H E E , A .
&
V a n W Y K , W . H u m a n P a p illo m a v iru s(H P V ) in o ra l S q u a m o u s C e ll p a p illo m a s . .1 . O ra l. P a th o I., 1 6 :
3 5 3 -3 5 5 , 1 9 8 7 .
5 4 . Z H O U , J. e t a lii. Id e n tific a tio n o f n u c le a r lo c a liz a tio n sig n a l o f
h u m a n p a p illo m a v iru s ty p e 1 6 L 1 p ro te in . V iro lo g y , 1 8 5 : 6 2 5
-6 3 2 , 1 9 9 1 .
5 5 . S A D O U L , G .
&
B E U R E T , T . A n a ly se d 'u n e se rie c o n tin u e d e4 2 1 c o n d y lo m e s g e n ita u x . E v o lu tio n , c o n d u ite e t re su lta ts
th e ra p e u tiq u e s . .T .G y n e c o l. O b ste t. B io I. R e p ro d ., 1 4 (8 ): 1 0 4 9
-1 0 5 8 , -1 9 8 5 .
5 6 . G L E W , S .
&
S T E R N , P L . H L A a n tig e n s a n d c e rv ic a l c a rc in o m a .N a tu re , 3 5 6 : 2 2 , 1 9 9 2 .
5 7 . B A R C E L L O S , J.M .P . e t a lii. C o lo u te rin o : e stu d o n a in fa n te ,
re c e m -n a sc id a e fe to . A lg u n s a sp e c to s c ito e h isto p a to l6 g ic o s.
R e v . B ra s. d e C a n c e ro lo g ia , 2 5 (3 ): 7 7 -9 5 , 1 9 7 5 .
5 8 . M A N D A L , D . e t a lii. P re v a le n c e o f o c c u lt h u m a n p a p illo m a v iru s
in fe c tio n , d e te rm in e d b y c y to lo g y a n d D N A h y b rid iz a tio n , in
h e te ro se x u a l m e n a tte n d in g a g e n ito u rin a ry m e d ic in e c lin ic . In t.
J.
S T D A ID S , 2 (5 ): 3 5 1 -5 , 1 9 9 1 .5 9 . R O B E R T S O N , 0 .1 . e t a lii. C e rv ic o -v a g in a l sc re e n in g in a n S T D
c lin ic . C a n .
J.
P u b lic . H e a lth , 8 2 (4 ): 2 6 4 -6 , 1 9 9 1 .60.
M IN C H E V A , A . e t a lii. D e te c tio n o f h u m a n p a p illo m a v iru s D N Ain g y n e c o lo g ic a l sw a b s b y filte r in situ h y b rid iz a tio n . A c ta . V iro I.
(P ra h a ), 3 5 (3 ): 2 0 9 -1 7 , 1 9 9 1 .
6 1 . N U O V O , G .J. e t a lii. H u m a n p a p illo m a v iru s se g re g a tio n p a tte rn s
in g e n ita l a n d n o n g e n ita l w a rts in p re p u b e rta l c h ild re n a n d a d u lts. A m .
J .
C lin . P a th o I., 9 5 : 4 6 7 -4 7 4 ,1 9 9 1 .6 2 . R E ID , R . e t a lii. S e x u a lly tra n sm itte d p a p illo m a v ira l in fe c tio n s.
A m . .T . O b ste t. G y n e c o I., 1 5 6 (1 ): 2 1 2 -2 2 2 , 1 9 8 7 .
6 3 . W IL S O N , R .W ., C H E N G G IS , M .L .
&
U N D E R , E .R .L o n g itu d in a l stu d y o f h u m a n p a p illo m a v iru s in fe c tio n o f th e
fe m a le u ro g e n ita l tra c t b y in situ h y b rid iz a tio n . A rc h . P a th o l.
L a b . M e d ., 1 1 4 : 1 5 5 -1 5 9 ,1 9 9 0 .
DIAS, E.P.; BARCELOS, J.M.P.; FONSECA, M.E.F. & BASSO, N.G.S. - Congenital papillomas and papillomatoses associated with the Human Papilloma Virus (HPV) - report on 5 cases
