O U R N A L
E d e n ils o n E d u a r d o C a lo r e , M a r ia J o s e C a v a lie r e , N e u z a K a s u m i S h ir a ta , M a r ia d e F a tim a A r a u jo
P a p illo m a v ir u s in c e r v ic o v a g in a l s m e a r s o f w o m e n
infected with Human Immunodefficiency Virus
P a t h o l o g i c a l A n a t o m y S e s s i o n o f t h e I n s t i t u t o E m t 1 i o R i b a s - P a t h o l o g y D e p a r t m e n t o f t h e
F a c u l d a d e d e M e d i c i n a d e S i i o P a u l o - P a t h o l o g y D i v i s i o n o f t h e I n s t i t u t o A d o l f o L u t z , S i i o P a u l o - S p , B r a z i l
It h a s b e e n d e s c rib e d th a t w o m e n in fe c te d w ith th e h u m a n im m u n o d e ffc ie n c y v iru s (H IV ) p re s e n t m o re fre q u e n t c y to lo g ic a l a b n o r-m a litie s in c e rv ic o v a g in a l s m e a rs , g e n e ra lly re la te d to in fe c tio n b y h u m a n p a p illo m a v iru s (H P V ). T h e p re s e n t w o rk is a s tu d y o f c e rv ic o v a g in a l s m e a rs o f 1 4 7 H IV -s e ro p o s itiv e w o m e n s u b m itte d to ro u tin e g y n e c o lo g ic a l e x a m in a tio n s . T h e s m e a rs w e re s ta in e d b y th e P a p a n ic o la o u m e th o d . C y to p a th ic e ffe c ts o f H P V w e re fo u n d in 3 8 (2 5 .8 % ) c a s e s . N u c le a r a ty p ia s o f c e rv ic a l in tra e p ith e lia l n e o p la s ia (C IN ) w e re e v id e n t in 3 6 (2 4 .5 % ) o f th e s e c a s e s : 2 7 (1 8 .4 % ), C IN I; 6 (4 .0 % ), C IN II a n d 3 (2 .0 % ) C IN III. A ls o 2 (1 .4 % ) in v a s iv e c a rc in o m a s a n d o n e (0 .7 % ) e n d o c e rv ic a l d y s p la s ia w e re fo u n d . O th e r a g e n ts o b s e rv e d w e re : C a n d id a s p , 1 9 (1 2 .9 % ) c a s e s ,' G a rd n e re lla v a g in a lis , 1 9 (1 2 .9 % ), T r ic h o m o n a s v a g in a lis , 1 3 (8 .4 % ), C h la m y d ia tr a c h o m a tis 5 (3 .4 % ), M o b ilu n c u s s p 2 (1 .4 % ) a n d H e rp e s s im p le x v iru s 1 (0 .7 % ). T h is s tu d y e m p h a s iz e s th e h ig h fre q u e n c y o f H P V /C IN c e rv ic o v a g in a l'a b n o rm a litie s in H IV -s e ro p o s itiv e in o u r p o p u la tio n . It is p o s s ib le th a t im m u n o lo g ic a l fa c to rs a n d s e x u a l p ro m is c u ity a re in v o lv e d in th is p h e n o m e n o n .
U N IT E R M S : H IV in fe c tio n . P a p illo m a v iru s in fe c tio n . C e rv ic a l in tra e p ith e lia l n e o p la s ia . C e rv ic a l n e o p la s ia .
IN T R O D U C T IO N
T
h e r eh u m a nh a sp a p i I I o m a v i r u s e sb e e n a g e n e r a l( H P V ) p l a y ac o n s e n s u s m a j o r c a u s a lt h a t g e n i t a l r o l e i n t h e d e v e l o p m e n t o f c e r v i c a l i n t r a e p i t h e l i a ln e o p l a s i a o r c e r v i c a l c a n c e r ( 2 , 9 , 1 1 , 1 2 ) . H P V t y p e s a n d
r i s k f a c t o r s , e s p e c i a l l y i m m u n e s t a t e , m a y a l s o p l a y
i m p o r t a n t r o l e s ( 9 ) . I t h a s b e e n d e s c r i b e d t h a t t h e r i s k o f
d e v e l o p i n g n e o p l a s t i c c h a n g e s i n t h e c e r v i x i s g r e a t e r i n
i m m u n o s u p p r e s s e d 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 .
A c q u i r e d I m m u n o d e f f i c i e n c y S y n d r o m e ( A I D S ) i s a r i s k
f a c t o r f o r p r e - n e o p l a s t i c / n e o p l a s t i c c e r v i c o v a g i n a l
A d d r e s s fo r c o r r e s p o n d e n c e : E d e n ils o n E d u a r d o G a lo r e
In s titu to d e In fe c to lo g ia E m flio R ib a s - S e 9 a O d e A n a to m ia P a to l6 g ic a - A v . D r . A r n a ld o , 1 6 5
S a o P a u lo /S P - B r a s il- G E P 0 1 2 4 6 - 0 0 1
d i s o r d e r s a s w e l l f o r H P V i n f e c t i o n s , s u b c l i n i c a l o r
s y m p t o m a t i c ( 2 , 1 0 ) . S q u a m o u s c e l l a t y p i a a n d c y t o l o g i c a l
s i g n s o f H P V i n f e c t i o n w e r e f o u n d i n w o m e n s e r o p o s i t i v e
f o r h u m a n i m m u n o d e f f i c i e n c y v i r u s ( H I V ) a t a
s i g n i f i c a n t l y h i g h e r r a t e w h e n c o m p a r e d t o s e r o n e g a t i v e
w o m e n ( 1 1 ) . I n t h e p r e s e n t w o r k , w e s t u d i e d s e r i e s o f 1 4 7
c e r v i c o v a g i n a l s m e a r s o f H I V - s e r o p o s i t i v e w o m e n ,
s u b m i t t e d t o r o u t i n e g y n e c o l o g i c a l e x a m i n a t i o n . T h e
s m e a r s w e r e s t a i n e d b y t h e P a p a n i c o l a o u m e t h o d a n d
a n a l y z e d t o s e a r c h f o r n u c l e a r c y t o l o g i c a l a b n o r m a l i t i e s ,
H P V c y t o p a t h i c e f f e c t s a n d o t h e r a g e n t s .
M A T E R IA L A N D M E T H O D S
O n e h u n d r e d f o r t y - s e v e n o u t p a t i e n t w o m e n ,
s e r o p o s i t i v e f o r H I V , i n d i f f e r e n t s t a g e s o f t h e d i s e a s e ,
C A L O R E , E .E .; C A V A L IE R E , M .J .; S H IR A T A , N .K . &A R A U J O , M .F . - P a p illo m a v iru s in c e rv ic o v a g in a l s m e a rs o f w o m e n in fe c te d w ith h u m a n im m u n o d e ffic ie n c y v iru s
1010
w ere su b m itted to ro u tin e g y n eco lo g ical ex am in atio n s. T h e
m ean ag e o f th e p atien ts w as 2 9 .6 y ears (ran g e 1 7 to 4 4 )
an d th e m ed ian 2 8 .9 y ears. S am p les o f cerv ico v ag in al
sm ears w ere stain ed b y th e P ap an ico lao u m eth o d an d
an aly zed b y th e D ep artm en t o f P ath o lo g y o f th e In stitu to '
d e In fecto lo g ia E m ilio R ib as (S ao P au lo ) in 1 9 9 4 , fro m
Jan u ary to D ecem b er, to search fo r sq u am o u s an d
en d o cerv ical cell n u clear ab n o rm alities, cy to p ath ic effects
o f p ap illo m av iru s (H P V ), an d o th er ag en ts. T h e
cy to lo g ical d iag n o sis w as b ased o n th e W H O classificatio n
(7 ). W e co n sid ered o n ly classical criteria (k o lilo cy to sis
an d d y sk erato sis) fo r d etectio n o f H P V 5 .
R E S U L T S
A m o n g 1 4 7 cases, cy to p ath ic effects o f H P V w ere
o b serv ed in 3 8 (2 5 .8 % ) cases. A m o n g th ese, 3 6 (2 4 .5 % )
sh o w ed ab n o rm alities related to cerv ical in traep ith elial
n eo p lasia (C IN ): 2 7 (1 8 .4 % ) C IN 1 ,6 (4 .0 % ) C IN II, an d
3 (2 .0 % ) C IN III. O th er tw o cases (1 .4 % ) sh o w ed in v asiv e
carcin o m a an d o n e, en d o cerv ical d y sp lasia. O th er ag en ts o b serv ed w ere: Candida sp, 1 9 cases (1 2 .9 % ), Gardnerella
vaginalis,19 (1 2 .9 % ), Trichomonas vaginalis, 1 3 (8 .4 % ),
Chlamydia trachomatis, 5 (3 .4 % ), Mobiluncus sp,2 (1 .4 % ) an d Herpes simplex virus, 1 (0 .7 % ).
D IS C U S S IO N
It h as b een d escrib ed th at w o m en in fected w ith H IV h av e g en ital H P V in fectio n s d etected b y so u th ern b lo t,
d o t b lo t, an d P C R m o re freq u en tly th an w o m en w ith o u t th e H IV in fectio n (2 ,3 ,1 2 ). In th e in tern atio n al m ed ical
literatu re, a h ig h er rate o f cerv ico v ag in al ab n o rm alities,
su ch as cerv ical in traep ith elial n eo p lasia (C IN ) asso ciated
w ith H P V , h av e also b een d escrib ed in cerv ico v ag in al sm ears (1 0 ).
In th e p resen t w o rk , w .e stu d ied a series o f 1 4 7
B razilian , H IV -in fected w o m en su b m itted to ro u tin e
g y n eco lo g ical ex am in atio n s. W e fo u n d 3 8 (2 5 .8 % ) cases
w ith cy to p ath ic effects o f H P V , 3 6 b ein g clearly e IN cases (2 7 C IN I, 6 C IN II an d 3 C IN III). W e fo u n d also tw o
cases o f carcin o m a, in w h ich H P V cy to p ath ic effects w ere
n o t ev id en t, p erh ap s b ecau se th e lesio n s w ere ad v an ced
an d o n ly m o re sen sitiv e tech n iq u es co u ld d etect H P V .
T h e freq u en cy o f H P V d etectio n b y cy to lo g y o f
cerv ico v ag in al sm ears in th e g en eral p o p u latio n referred
in rep o rts o f th e in tern atio n al literatu re is n ear 2 % (6 ,8 ). In th e H ealth P u b lic S erv ice o f S ao P au lo S tate, th e
freq u en cy o f H P V fC IN in w o m en screen ed b y
cerv ico v ag in al sm ears is sim ilar. T h e A d o lfo L u tz In stitu te
screen ed 1 1 2 ,8 0 4 cerv ico v ag in al sm ears (fro m 1 9 9 0 to
1 9 9 1 ) an d fo u n d 1 .5 % o f H P V fC IN -related cases (4 ).
C o n sid erin g th e freq u en cy o f H P V fC IN d etectio n b y
cerv ico v ag in al cy to lo g y in g en eral p o p u latio n , th e h ig h er
freq u en cy o f th ese lesio n s in o u r series o f H IV -in fected
w o m en is u n q u estio n ab le.
S ch rag er et al. (1 0 ), in 1 9 8 9 , an d V erm u n d et al.
( II) , in 1 9 9 1 , fo u n d th at th e freq u en cy o f H P V in fectio n an d sq u am o u s in traep ith elial.lesio n s is g reater in H IV
-sero p o sitiv e w o m en th an in h ig h risk H IV -sero n eg ativ e
w o m en . B ased o n th ese d ata, it is p o ssib le to su p p o se th at
th ere are o th er facto rs b esid es sex u al p ro m iscu ity in v o lv ed
in th e g reater freq u en cy o fH P V in fectio n in H IV -in fected
w o m en .
T h e m ech an ism o f in d u ctio n o f H P V -m ed iated
cerv ical p re-m alig n an t lesio n s in H IV -in fected w o m en
is u n clear.
It is p o ssib le th at im m u n o d efficien cy m ay fav o r th e
rep licatio n o f H P V . In th is co n tex t, B arto n et al. ( I) fo u n d
a d ep letio n o f th e L an g erh an s cells in th e ep ith elial tiss'u e
o f w o m en w ith H IV
A d irect in teractio n b etw een H IV an d H P V at th e
cellu lar lev el, lead in g to tran sactiv atio n , o f v iral rep licatio n
h as also b een p ro p o sed (9 ).
F u rth er stu d ies m ay elu cid ate th ese m ech an ism s. . N ev erth eless, th e p resen t d ata stro n g ly su g g est th at H IV
-in fected w o m en h av e a h ig h er risk o f H P V in fectio n asso ciated o r n o t w ith p re-n eo p lastic/n eo p lastic lesio n s o f
th e cerv ix , an d carefu l an d freq u en t g y n eco lo g ical
ex am in atio n s m u st b e reco m m en d ed fo r th is p o p u latio n .
1011
R E S U M O
In tro d u y 8 o : T e m s id o re la ta d o q u e m u lh e re s in fe c ta d a s p e lo H IV a p re s e n ta m m a io r in c id e n c ia d e a tip ia s c ito l6 g ic a s n o s e s fre g a y o s cervico-vaginais, re la c io n a d a s p rin c ip a lm e n te c o m a in fe c y 8 0 p e lo H P V . M a te ria l e M e to d o s : Q p re s e n te tra b a lh o re p re s e n ta 0 e s tu d o d e e s fre g a g o s c e rv ic o -v a g in a is d e 1 4 7 m u lh e re s H IV -s o ro p o s itiv a s , s u b m e tid a s a e x a m e g in e c o l6 g ic o d e ro tin a . O s e s fre g a y o s fo ra m c o ra d o s p e lo m e to d o d e P a p a n ic o la o u . S in a is c ito p a tic o s d e in fe c y8 0 p a r H P V fo ra m e n c o n tra d o s e m 3 8 (2 5 ,8 % ) c a s o s . R e s u lta d o s : A tip ia s n u c le a re s d e n e o p la s ia in tra -e p ite lia l cervical fo ra m evidentes e m 3 6 (2 4 ,5 % ) . d e s te s c a s o s s e n d o 2 7 (1 8 ,4 % ) g ra u I (N IC I), 6 (4 ,0 % ) N IC II e 3 (2 ,0 % ) N IC III.Qbservaram-se 2 (1 ,4 % ) c a s o s d e c a rc in o m a in v a s o r e 1 (0 ,7 % ) d e d is p la s ia endocervical. Q u tro s a g e n te s e n c o n tra d o s fo ra m : Candida sp,1 9 c a s o s (1 2 ,9 % ). Gardnerella
vagina/is, 1 9 (1 2 ,9 % ), Trichomonas vagina/is, 1 3 (8 ,4 % ), Chlamydia trachomatis, 5 (3 ,4 % ), Mobiluncus sp,2 (1 ,4 % ) e Herpes
simp/ex v iru s , 1 (0 ,7 % ). C o n c lu s 8 o : E s te e s tu d o re s s a lta a a lta in c id e n c ia d e H P V /N IC e m p a c ie n te s H IV -p o s itiv a s e m h o s s o
m e io . Eprovavel q u e fa to re s im u n o l6 g ic o s e p ro m is c u id a d e e s te ja m envolvidos n e s te fe n 6 m e n o .
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