Involvement of Canine Oral Papillomavirus in Generalized Oral and Cutaneous Verrucosis in a Chinese Shar Pei Dog

Abstract

Severe papillomatosis developed in the oral cavity and spread throughout the haired skin of the trunk and limbs of an 8-month-old female Chinese Shar Pei dog. The dog had received corticosteroids prior to referral, which was associated with the onset of demodecosis and papillomatosis. Papillomavirus structural antigens were detected in biopsies by immunohistochemistry using a panel of monoclonal and polyclonal antibodies. An 8.2-kilobase papillomavirus-specific DNA molecule was detected in the cutaneous lesions by high stringency Southern blot hybridization using a cloned canine oral papillomavirus DNA probe. Restriction enzyme analysis revealed that the virus in the cutaneous lesions was identical to the canine oral papillomavirus. Discontinuation of the steroids combined with the use of a mitocide, antibiotics, and an autogenous vaccine resolved the demodecosis and papillomatosis. This case report suggests that corticosteroid-induced immunosuppression can expand the tissue tropism of papillomaviruses.

Full text

http://vet.sagepub.com/
Veterinary Pathology Online
http://vet.sagepub.com/content/31/2/183
The online version of this article can be found at:
DOI: 10.1177/030098589403100204
1994 31: 183Vet Pathol
J. P. Sundberg, E. K. Smith, A. J. Herron, A. B. Jenson, R. D. Burk and M. Van Ranst
Shar Pei Dog
Involvement of Canine Oral Papillomavirus in Generalized Oral and Cutaneous Verrucosis in a Chinese
Published by:
http://www.sagepublications.com
On behalf of:
Pathologists.
American College of Veterinary Pathologists, European College of Veterinary Pathologists, & the Japanese College of Veterinary
can be found at:Veterinary Pathology OnlineAdditional services and information for
http://vet.sagepub.com/cgi/alertsEmail Alerts:
http://vet.sagepub.com/subscriptionsSubscriptions:
http://www.sagepub.com/journalsReprints.navReprints:
http://www.sagepub.com/journalsPermissions.navPermissions:
by guest on July 12, 2011vet.sagepub.comDownloaded from

Vet
Pathol
31:183-187 (1994)
Involvement
of
Canine Oral Papillomavirus in
Generalized Oral and Cutaneous Verrucosis in a
Chinese Shar Pei
Dog
J.
P.
SUNDBERG,
E.
K.
SMITH,
A.
J.
HERRON,
A.
B.
JENSON,
R.
D.
BURK,
AND
M.
VAN
RANST
The Jackson Laboratory, Bar Harbor, ME; Animal Dermatology Clinic, Animal Hospital by the Lake,
West Palm Beach,
FL;
Department of Pathology, University of Miami School of Medicine, Miami, FL;
Department of Pathology, Georgetown University School of Medicine, Washington, DC; and
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx,
NY
Abstract.
Severe papillomatosis developed in the oral cavity and spread throughout the haired skin of the
trunk and limbs of an 8-month-old female Chinese Shar Pei dog. The dog had received corticosteroids prior to
referral, which was associated with the onset of demodecosis and papillomatosis. Papillomavirus structural
antigens were detected
in
biopsies by immunohistochemistry using a panel of monoclonal and polyclonal
antibodies. An 8.2-kilobase papillomavirus-specific DNA molecule was detected in the cutaneous lesions by
high stringency Southern blot hybridization using a cloned canine oral papillomavirus DNA probe. Restriction
enzyme analysis revealed that the virus in the cutaneous lesions was identical to the canine oral papillomavirus.
Discontinuation of the steroids combined with the use of a mitocide, antibiotics, and an autogenous vaccine
resolved the demodecosis and papillomatosis. This case report suggests that corticosteroid-induced immuno-
suppression can expand the tissue tropism of papillomaviruses.
Key
words:
Papillomavirus; skin; immunosuppression; steroids; oral cavity.
The papillomaviruses are a large group
of
species-
specific, double-stranded
DNA
viruses that infect a
wide variety of vertebrate hosts, including man.33 In
dogs, papillomaviruses are known to cause benign pap-
illomas of the skin as well as the oral, ocular, and
genital mucous membranes.27
To
date, only the ge-
nome of the canine oral papillomavirus (COPV) has
been cloned and chara~terized.~~ Based on transmis-
sion, immunohistochemistry, and in situ hybridization
studies, it is believed that more than one papilloma-
virus infects the dog and that each virus has a tropism
for a specific anatomic site.27
Florid oral papillomas in Beagle dogs has been as-
sociated with an
IgA deficiency (Sundberg, unpub-
lished data).29.3n Rare case-studies document that dogs
with florid oral papillomas developed small, solitary
papillomas on the planum nasale, but not widespread
lesions on the haired
kin.^",^^
We report extensive papillomatosis
of
the haired
skin as well as the oral mucosa in an iatrogenically
immunosuppressed Chinese Shar Pei dog. The COPV
was identified by restriction fragment analysis as the
virus present in the cutaneous lesions. The presence
of
an oral papillomavirus in cutaneous lesions in an
immunosuppressed host raises the possibility that the
tissue specificity of papillomaviruses is influenced by
the immune system.
Materials and Methods
Clinical
history
An 8-month-old, 20-kg female Chinese Shar Pei dog was
referred (to
EKS)
with alopecia, erythematous suppurative
dermatitis, and generalized exophytic papillomatosis of the
oral mucosa as well as the truncal and appendicular haired
skin. The papillomas had been present for
4
months. A lit-
termate had died with severe oral papillomatosis. In the same
littermate, oral papillomas had been removed surgically by
the attending veterinarian but the lesions had recurred rap-
idly. In the dog described here, skin scrapings demonstrated
the presence of mites
(Demodex
canis),
which were respon-
sible for generalized demodectic mange, complicated by sec-
ondary bacterial infection. The dog had initially been main-
tained
for
prolonged periods on corticosteroids (prednisone,
5
mg bid.; Best, Miami, FL) and antibiotics (cefadroxil,
400
mg bid.; Fort Dodge, Fort Dodge, IA). This suggested that
both dogs might have suffered a hereditary immunodeficien-
cy that was complicated by iatrogenic corticosteroids in the
second animal. Serum protein electrophoresis revealed de-
creased gamma globulin
(0.56;
normal 0.9-2.2
g/lOO
ml) and
beta globulin (1.21; normal 1.3-2.7
g/100
ml), supporting
this observation. Discontinuation
of
the corticosteroids, in-
stitution of cephradine
(500
mg bid.; Biocraft, Elmwood
Park, NJ), and weekly dipping with amitraz (Mitaban, Up-
john
Co.
Kalamazoo,
MI)
cleared the pyoderma and
De-
modex
infestation such that regrowth
of
hair occurred in 2
months. An autogenous papillomavirus vaccine was pre-
183
by guest on July 12, 2011vet.sagepub.comDownloaded from

I84
Sundberg,
Smith,
Herron, Jenson,
Burke,
and Van Ranst
Vet
Pathol
312,
1994
pared (Dr.
J.
Gaskin, University of Florida, Gainesville) and
administered
2
months after referral. However, the papil-
lomas were already undergoing changes indicative of regres-
sion (dessication and exfoliation),
so
it is unclear if the vac-
cine had any effect. The papillomas cleared within
3
months,
leaving no residual scarring. After 2 years of follow-up, the
dog remains free of papillomas, demodecosis,
or
other skin
lesions.
Tissues
Full
thickness biopsies from eight cutaneous tumors were
surgically removed from the neck and the truncal skin. The
tissues were bisected, with representative portions fixed in
10%
neutral buffered formalin, embedded in paraffin, sec-
tioned at
3-5
Fm, and stained with hematoxylin and eosin
(HE) for light microscopic examination. The remaining
por-
tions were frozen on dry ice and stored
at
-80
C for DNA
extraction.
Irnrnunohistochernistry
Serial, 6-pm sections from cutaneous tumors were stained
for papillomavirus antigenic epitopes using the avidin-biotin
peroxidase complex method (Vector Laboratories, Burlin-
game, CA) with diaminobenzidine (Sigma Chemical Co., St.
Louis, MO)
as
the chromogen and Mayer’s hematoxylin
as
the counterstain,
as
previously described.lh-LX A broadly cross-
reactive rabbit polyclonal antibody
(DAKO
Corp.,
Carpin-
teria, CA)29 and
a
panel of mouse monoclonal antibodies
directed against specific papillomavirus epitopesIh were used.
A canine
oral
papilloma, experimentally induced with char-
acterized canine
oral
papillomavirus (COPV)? was used
as
a
positive control substrate.
DNA
extraction
Frozen papillomas were finely minced and incubated at
37
C
for 18 hours in
SO
mM Tris-HCI, pH 8.6,
50
mM ethyl-
enediaminetetraacetic acid (EDTA), pH 8.0, containing
0.4%
sodium dodecyl sulfate (SDS) and
0.5
mg/ml of proteinase
K (Boehringer Mannheim, Indianapolis. IN). Contaminating
RNA was removed by digestion with
S
U/ml DNase free
RNase (Boehringer Mannheim) for
1
hour at
37
C.
The lysate
was extracted twice with equal volumes of pheno1:chloroform
(1:
l), then twice with chloroform alone. DNA was precipi-
tated with one volume of absolute ethanol and one volume
of isopropanol, air-dried, and redissolved in TE buffer (10
mM Tris-HCI, pH 8.0,
1
mM EDTA).
Restriction enzyme cleavage and Southern
blot hybridization
Cellular DNA
(5
pg) was digested with restriction endonu-
cleases
according to the manufacturer’s recommendation
(Boehringer Mannheim; New England Biolabs, Beverly, MA).
The resulting fragments were electrophoretically separated
through horizontal
1
.O%
agarose gels (FMC Bioproducts,
Rockland, ME), acid depurinated in
0.25
N HCI, denatured,
neutralized, and transferred under alkaline conditions to
a
Nytran charge-modified nylon membrane (Schleicher
&
Schuell, Keene, NH) by the method of Southern.” The DNA
was immobilized to the solid support by baking for
1
hour
at
80
C
in
a
vacuum oven.
Cloned COPV DNA3” was digested with
Eco
RI and sep-
arated from the pBR322 vector by electrophoresis in
a
1.0%
agarose gel. Linearized COPV DNA was purified from the
gel using the Geneclean method (Bio
10
1,
La
Jolla,
CA). The
COPV DNA was radiolabeled using the random primer ex-
tension method* with
3000
Ci/mM deoxycytidine 5’-(a3?P)-
triphosphate (Amersham, Arlington Heights, IL). Specific
activity ofthe probe was about
1
O8
cpm/pg. Prehybridization,
hybridization, and post-hybridization washing of the mem-
brane were done according to standard procedures.?? The
filter was exposed to Kodak XAR-5 x-ray film (Eastman
Kodak, Rochester,
NY)
for
1
to
5
hours
-70
C using inten-
sifying screens (Cronex Lightning-Plus. E.I. du Pont de
Nemours
&
Co.,
Inc., Wilmington, DE).
Results
Gross lesions
Firm, pale to lightly pigmented, verrucous masses
were present throughout the oral cavity, labia, and
extending to the haired skin. Cutaneous lesions were
similar in appearance and were pigmented light brown,
similar to the color of the dog’s skin. The cutaneous
lesions were located throughout the haired skin. Le-
sions ranged from
0.5
to
2.0
cm in diameter (Fig.
1).
Microscopic features
and
irnrnunohistochernistry
Microscopically, the lesions were proliferative, ex-
ophytic papillomas consisting of marked epidermal hy-
perplasia on thin fibrovascular stalks (Fig.
2).
Koilo-
cytes were located in the upper stratum granulosum
extending into the lower layers
of
the stratum corneum
(Fig,
3).
Small, single
or
multiple, amphophilic intra-
nuclear structures resembled inclusions. The koilo-
cytes stained positively by immunohistochemistry
for
papillomavirus group-specific antigens and papillo-
mavirus specific epitopes that have been previously
reported to be present in the canine oral papilloma-
virus (Fig.
4).16
Southern transfer hybridization
Total DNA extracts from the cutaneous tumors were
hybridized under high stringency conditions (Tm
=
15
C,
i.e.,
15
C
below the DNA duplex melting temper-
ature) with a
COPV
DNA probe (Fig.
5).
Undigested
DNA revealed the presence
of
unintegrated viral ge-
nomes. Digestion with
Eco RI
and
Cla
I
linearized the
DNA. The length of the viral genome was
8.2
kilobase
pairs. Two fragments were generated with
Pvu
I1
and
Ava
I,
three with
Barn
HI,
and four with
Hinc
11.
This
pattern is identical to the previously published restric-
tion map for
COPV
DNA.30 The strong hybridization
signals under high stringency conditions, in addition
to DNA restriction patterns identical to those pub-
by guest on July 12, 2011vet.sagepub.comDownloaded from

Vet
Pathol
31:2,
1994
Oral and Cutaneous
Dog
Papillomas
185
Fig.
1.
Fig.
2.
Fig.
3.
Fig.
4.
Face; Chinese Shar Pei dog. Florid oral (arrowheads) and cutaneous papillomas.
Skin; Chinese Shar Pei dog. Exophytic papilloma.
HE.
Bar
=
1
mm.
Skin; Chinese Shar Pei dog. Koilocytes (arrowheads) in the upper stratum spinosum and lower stratum corneum.
Skin; Chinese Shar Pei dog. Nuclei (arrowheads), positive
for
papillomavirus group-specific antigens
in
koilocytes.
HE.
Bar
=
50
pm.
Avidin-biotin peroxidase complex method, light green counterstain. Bar
=
25
pm.
lished for COPV, indicate that the papillomavirus iso-
lated from the cutaneous lesions of the immunosup-
pressed Shar Pei dog is identical to, or an extremely
related variant of the common COPV.
Discussion
DNA
extracted from cutaneous papillomas of an
immunosuppressed Chinese Shar Pei dog contained
papillomaviral
DNA
with a restriction pattern consis-
tent with the canine oral papillomavirus (COPV), which
has been previously characterized and found in many
geographical regions.21,26,29,30 The COPV is the only dog
papillomavirus that has had its genome cloned and
chara~terized.~'.~~ However, transmission studies, im-
munohistochemistry, and in situ hybridization meth-
ods have suggested that the
dog
may be infected by
four or more distinct papillomavir~ses.~~ Published
photographs have demonstrated canine papillomas ex-
tending from the oral labia up the planum nasale, but
not extending far into the haired ~kin.*O.~~ This is the
first report, to the best of our knowledge, that clearly
demonstrates that the COPV can infect and cause pap-
illomas
of
the haired skin. The history provided to us
by the owner indicated that a littermate was severely
by guest on July 12, 2011vet.sagepub.comDownloaded from

I86
Sundberg,
Smith,
Herron,
Jenson,
Burke,
and
Van
Ranst
Vet
Pathol
3
12,
1994
Fig.
5.
Southern blot; cutaneous papilloma from a Chi-
nese Shar Pei dog. High stringency Southern blot of total
cellular DNA, undigested
(Fig.
5A)
or
digested with
Eco
RI
(Fig.
5B),
Clu
I
(Fig.
50,
Barn
HI
(Fig.
5D),
Pw
I1
(Fig.
5E),
Avu
I
(Fig.
5F),
or
Hinc
I1
(Fig.
5G),
probed with
a
radiolabeled canine oral papillomavirus probe.
affected as well. This suggests that both dogs had a
hereditary immunodeficiency that was complicated by
prolonged use of steroids.
IgA
deficiency has been re-
ported in at least two colonies of Chinese Shar Pei
dogs.I9 One dog had sinopulmonary abnormalities and
developed demodecosis. Reduced concentrations
of
IgA
have also been associated with oral papillomatosis in
line bred Beagle
dogs,ll
some of which had received a
highly efficacious live COPV vaccine as pups (Sund-
berg, unpublished data).29,30
This case report provides evidence that immuno-
suppression due
to
or complicated by prolonged use
of corticosteriods can exacerbate latent papillomavirus
infections and can cause an expansion in the tissue
tropism
of
the virus. This raises the possibility that the
tissue specificity
of
papillomaviruses
is
influenced by
the immune system. Whereas different papillomavirus
types show a predilection for particular anatomical sites,
exceptions have been noted, particularly in human be-
ings. Human papillomavirus (HPV) type
7,
a
virus only
found in common hand warts of healthy butchers and
meat handlers, was recovered from oral lesions in HIV-
seropositive patients.12.31
In
some immunodeficient pa-
tients, the lesions were, apart from the oral mucosa,
also found in the facial skin.6 HPV type
2,
a derma-
totrophic papillomavirus usually associated with com-
mon hand warts, has also been identified in oral mu-
cosal Human patients with congenital or
acquired disorders of the cell-mediated or humoral
immune system have an increased prevalence of pap-
illomavirus-induced lesions.
I3,I7
Renal allograft recip-
ients, receiving long-term immunosuppressive treat-
ment to prevent transplant rejection, had an increased
prevalence (range from 24 to
77%) and seventy of
persistent and treatment-resistant cutaneous
warts.3.10.14,15.18,24 Some authors reported malignant
transformation
of
some of the warty
lesion^.^.^^
An
increased incidence of cervical premalignant and ma-
lignant lesions attributed
to
HPV infection has been
reported in women with renal transplants receiving
immunosuppressive therapy.2 If HPV-associated le-
sions were found in multiple genital organ sites, a sub-
clinical immunodeficiency of unknown etiology was
often found.5 Subsequently, it has been shown that HIV
immunosuppressed women manifest a higher inci-
dence and advanced pathologic consequences of cer-
vicovaginal HPV infection. Immunosuppressed wom-
en often respond poorly to conventional treatment
of
HPV-induced
lesion^.^,^^
This case report of florid oral and cutaneous papil-
lomatosis in an immunosuppressed dog, with a review
of
similar phenomenon in human beings, provides ad-
ditional evidence that the papillomavirus-induced neo-
plasms in other species can serve as models to deter-
mine the complicated pathogenesis of these diseases.
Acknowledgements
The authors thank P. Jewett for performing the immu-
nohistochemistry. M. Van Ranst is a fellow of the Belgian
American Educational Foundation and of the University of
Leuven D. Collen Research Foundation.
References
1
Adler-Storthz
K,
Newland JR, Tesin BA, Yeudall WA,
Shillitoe
E:
Human papillomavirus type 2 DNA in oral
verrucous carcinoma. J Oral Pathol Med 15472-475,
1986
2 Alloub MI, Barr BB, McLaren
KM,
Smith IW, Bunney
MH, Smart
GE:
Human papillomavirus infection and
cervical intraepithelial neoplasia in women with renal
allografts. Br Med
J
298:153-156, 1989
3
Barnett N, Mak H, Winkelstein JA: Extensive verrucosis
in primary immunodeficiency diseases. Arch Dermatol
119:5-7, 1983
4
Barr BB, Benton
EC,
McLaren
K,
Bunney MH, Smith
IW, Blessing
K,
Hunter JAA: Human papillomavirus
infection and skin cancer in renal allograft patients. Lan-
cet i:124-129, 1989
5
Carson
LF,
Twiggs LB, Fukushima M, Ostrow RS, Faras
AJ, Okagaki
T:
Human genital papilloma infections: an
evaluation of immunologic competence in the genital
neoplasia-papilloma syndrome. Am J Obstet Gynecol
6 de Villiers
EM:
Prevalence
of
HPV 7 papillomas in the
oral
mucosa and facial skin of patients with human im-
155~784-789, 1986
by guest on July 12, 2011vet.sagepub.comDownloaded from

Vet
Pathol
31:2,
1994
Oral and Cutaneous
Dog
Papillomas
187
munodeficiency virus. Arch Dermatol 125: 1590, 1989
7
de Villiers EM, Weidauer H, Otto H,
zur
Hausen H:
Papillomavirus DNA in human tongue carcinomas. Int
J Cancer 36575-578, 1985
8
Feinberg AP, Volgelstein
B:
A technique for radiola-
belling DNA restriction endonuclease fragments to high
specific activity. Anal Biochem 132:6-13, 1983
9 Feingold AR, Vermund SH,
Burk
RD, Kelley KF, Schra-
ger LK, Schreiber
K,
Munk G, Friedland GH, Klein RS:
Cervical cytologic abnormalities and papillomavirus in
women infected with human immunodeficiency virus.
J
10
Gassenmaier A, Fuchs P, Schell H, Pfister H: Papillo-
mavirus DNA in warts of immunosuppressed renal al-
lograft recipients. Arch Dermatol Res 278:2 19-223, I986
1
1 Glickman LT, Shofer FS, Payton AJ, Laster LL, Felsburg
PJ:
Survey of serum IgA,
IgG,
and IgM concentrations
in a large beagle population in which IgA deficiency had
been identified. Am J Vet Res 49: 1240-1245, 1988
12
Greenspan G, de Villiers EM, Greenspan
JS,
De Souza
YG,
zur
Hausen H: Unusual HPV types in oral warts
in association with HIV infection. J Oral Pathol 17:482-
487,
1988
13
Jablonska S, Orth G, Lutzner MA: Immunopathology
of papillomavirus-induced tumors in different tissues.
Springer Semin Immunopathol 533-62, 1982
14 Koranda FC, Dehmel EM, Kahn G, Penn
I:
Cutaneous
complications in immunosuppressed renal homograft
re-
cipients.
J
Am Med Assoc 229:419-424, 1974
15 L‘Eplattenier JL, Binswanger
U,
Ott F, Largiader F: Der-
matologische komplikationen bei immunosupprimierten
nach nierentransplantation. Schweiz med Wschr 110:
16 Lim PS, Jenson AB, Cowsert
L,
Nakai Y, Lim LY, Jin
XW, Sundberg JP: Distribution and specific identifi-
cation of papillomavirus major capsid protein epitopes
by immunocytochemistry and epitope scanning
of
syn-
thetic peptides. J Infect Dis 162: 1263-1 269, 1990
17 Lutzner MA: Papillomavirus lesions in immunodepres-
sion and immunosuppression. Clin Dermatol3: 165-1 69,
1985
18
McLelland
J,
Rees A, Williams G, Chu T: The incidence
of immunosuppression-related skin disease in long-term
transplant patients. Transplantation 46:87 1-874, 1988
19 Moroff SD, Hurvitz AI, Peterson ME, Saunders L, Noone
KE: IgA deficiency in Shar Pei dogs. Vet Immunol Im-
munopathol 133181-188, 1986
20 Olson C: Animal papillomas, historical perspectives.
In:
The Papovaviridae. 2. The Papillomaviruses,
ed.
AIDS 3~896-903, 1990
1307-1 3
13,
1980
Salzman NP and Howley PM,
pp.
39-66. Plenum Press,
New York, NY, 1987
2
1
Pfister H, Meszaros J: Partial characterization of canine
oral papillomavirus. Virology 104:243-246, 1980
22
Sambrook
J,
Fritsch EF, Maniatis
T:
Molecular cloning:
a laboratory manual. Cold Spring Harbor Laboratory,
Cold Spring Harbor, NY, 1989
23
Southern EM: Detection of specific sequences among
DNA fragments separated by gel electrophoresis. J Mol
Biol 98:S03-5 17, 1975
24 Spencer
ES,
Andersen HK: Viral infections in renal al-
lograft recipients treated with long-term immuno-
suppression. Br Med J 2:829-830, 1979
25 Sundberg JP: Diagnostic exercise: multiple white masses
in the mouth of Beagles. Lab Anim Sci 37:339-340. 1987
26 Sundberg JP, Reszka AA, Williams
ES,
Reichmann ME:
An
oral
papillomavirus that infected
one
coyote and three
dogs. Vet Pathol 28:87-88, 199
1
27 Sundberg JP: Canine papillomaviruses.
In:
Veterinary
Diagnostic Virology: A Practitioner’s Guide, ed. Castro
AE and Heuschele WP,
pp.
148-1
SO.
Mosby Year Book,
St. Louis, MO 1992
28 Sundberg JP, Junge RE, Lancaster WD: Immunoperox-
idase localization
of
papillomaviruses in hyperplastic and
neoplastic epithelial lesions
of
animals. Am J Vet Res
29 Sundberg JP, O’Banion MK: Animal papillomaviruses
associated with malignant tumors. Adv Viral Oncol
8:
30 Sundberg JP, O’Banion MK, Schmidt-Didier E, Reich-
mann ME: Cloning and characterization of a canine oral
papillomavirus. Am
J
Vet
Res
47: 1142-1 144, 1986
31
Syrjanen SM, von Krogh G, Kellokoski J, Syrjanen K:
Two different human papillomavirus types associated
with oral mucosal lesions in an HIV-seropositive man.
J Oral Pathol Med 18:366-370, 1989
32 Turner JE, Hodge SJ, Callen
P:
Verrucous carcinoma in
a renal transplant patient after long-term immuno-
suppression. Arch Dermatol 116: 1074-1076, 1980
33
Van Ranst M, Kaplan JB, Burk RD: Phylogenetic clas-
sification
of
human papillomaviruses. J Gen Virol
73:
34 Vermund SH, Kelly KF, Klein RS, Feingold AR, Schrei-
ber K, Munk G, Burk RD: High risk
of
human papil-
lomavirus infection and cervical squamous intraepithe-
lial lesions among women with symptomatic human
immunodeficiency virus infection. Am J Obstet Gynecol
165392-400, 1991
45: I44 1-1446, 1984
55-71,
1989
2653-2660, 1992
Request reprints from Dr. Marc Van Ranst, Albert Einstein College of Medicine, Ullmann Building, Room
5
15, 1300
Morris Park Avenue, Bronx, New York, NY 1046
1
(USA).
by guest on July 12, 2011vet.sagepub.comDownloaded from