RRP Medical Reference Service





An RRP Foundation Publication


edited by


Dave Wunrow and Bill Stern






















Winter 1997



Volume 4 • Number 1













The RRP Medical Reference Service is intended to be of potential interest to RRP patients/families seeking treatment, practitioners providing care, micro biological researchers as well as others interested in developing a comprehensive understanding of recurrent respiratory papillomatosis.

This issue focuses on a selection of references (most) with abstracts from recent (1995 and later) RRP related publications.These listings are sorted in approximate reverse chronological order as indicated by the "Unique Identifier" numbers. Each listing is formatted as follows:
Primary affiliation (when specified)
Language (if it is not specified assume article is in English)
Journal or reference
Unique identifier

If copies of complete articles are desired, we suggest that you request a reprint from one of the authors. If you need assistance in this regard or if you have any other questions or comments please feel free to contact:

Bill Stern
RRP Foundation
P.O. Box 6643
Lawrenceville NJ 08648-0643
E-mail: billslins@aol.com or wfs@gfdl.gov

Dave Wunrow
210 Columbus Drive
Marshfield WI 54449
(715) 387-8824
E-mail: wunrow@tznet.com


RRPF Selected Articles and Abstracts



Bradlow HL; Telang NT; Sepkovic DW; Osborne MP

2-hydroxyestrone: the 'good' estrogen.

Strang Cancer Research Laboratory, New York, New York 10021, USA.

Source: J Endocrinol 1996 Sep;150 Suppl:S259-65

Unique Identifier: 97099229


The issue of the role of 2-hydroxyestrone (2-OHE1) in breast
cancer has been the subject of considerable controversy as to
whether it is carcinogenic or anticarcinogenic. The expanding
data base outlined below is most consistent with the conclusion
that 2-OHE1 is anticarcinogenic. In every experimental model in
which 2-hydroxylation was increased, protection against tumors
was achieved. Correspondingly, when 2-hydroxylation was
decreased, an increase in cancer risk was observed. Even more
dramatically, in the case of laryngeal papillomas induction of
2-hydroxylation with indole-3-carbinol (I3C) has resulted in
inhibition of tumor growth during the time that the patients
continue to take 13C or vegetables rich in this compound.


Erisen L; Fagan JJ; Myers EN

Late recurrences of laryngeal papillomatosis.

Department of Otolaryngology-Head and Neck Surgery, Uludag Universitesi Tip Fakultesi, Bursa, Turkey.

Source: Arch Otolaryngol Head Neck Surg 1996 Sep;122(9):942-4

Unique Identifier: 96390571


Laryngeal papillomotasis recurred in 2 patients after 44 and 47
years of remission. The recurrence of papillomatosis after such
lengthy periods of remission underscores the fact that, while
surgical treatment of laryngeal papillomatosis may maintain the
airway and voice, and in some cases control clinically overt
disease, it does not address the subclinical mucosal human
papillomavirus infection that may lead to recurrence many years
after surgery.


Jakubikova J; Zitnan D; Batorova A

An unusual reason for obstructive sleep apnea in a boy with

hemophilia B: supraglottic papilloma.

Pediatric Otolaryngologic Clinic, University Comenius Bratislava, Slovak Republic.

Source: Int J Pediatr Otorhinolaryngol 1996 Jan;34(1-2):165-9

Unique Identifier: 96366508


An unusual cause of obstructive sleep apnea in a boy with
hemophilia B who was urgently intubated during the night because
of suspected bleeding into the airway is analysed. The cause of
airway obstruction was a floating papilloma hanging from false
cord. At inspirium the tumor was moving immediately above the
vocal cords. This was manifested during sleep by noisy snoring
and numerous apneic pauses. When the child was awake he had no
respiratory problems. After the tumor was removed, the boy
breathed freely during sleep. However, the papillomas recur in
various parts of the larynx and repeated surgical treatment by
factor IX replacement: therapy is necessary.


Kelloff GJ; Boone CW; Crowell JA; Nayfield SG; Hawk E; Steele VE; Lubet RA; Sigman CC

Strategies for phase II cancer chemoprevention trials: cervix,
endometrium, and ovary.

Chemoprevention Branch (CB), Division of Cancer Prevention and Control (DCPC), National Cancer Institute (NCI), National

Source: J Cell Biochem Suppl 1995;23:1-9

Unique Identifier: 96363269


Well-designed and conducted Phase II clinical trials are very
important to cancer chemoprevention drug development. Three
critical aspects govern the design and conduct of these
trials--well-characterized agents, suitable cohorts, and reliable
biomarkers for measuring efficacy that can serve as surrogate
endpoints for cancer incidence. Requirements for the agent are
experimental or epidemiological data showing chemopreventive
efficacy, safety on chronic administration, and a mechanistic
rationale for the chemopreventive activity observed. Agents that
meet these criteria for chemoprevention of cervical cancer
include antiproliferative drugs (e.g.,
2-difluoromethylornithine), retinoids, folic acid, antioxidant
vitamins and other agents that prevent cellular oxidative damage.
Because of the significant cervical cancer risk associated with
human papilloma virus (HPV) infection, agents that interfere with
the activity of HPV products may also prove to be effective
chemopreventives. In endometrium, unopposed estrogen exposure has
been associated with cancer incidence. Thus, pure antiestrogens
and progestins may be chemopreventive in this tissue. Ovarian
cancer risk is correlated to ovulation frequency; therefore, oral
contraceptives are potentially chemopreventive in the ovary.
Recent clinical observations also suggest that retinoids,
particularly all-trans-N-4-hydroxyphenylretinamide, may be
chemopreventive in this tissue. The cohort should be suitable for
measuring the chemopreventive activity of the agent and the
intermediate biomarkers chosen. In the cervix, patients with
cervical intraepithelial neoplasia (CIN) and in endometrium,
patients with atypical hyperplasia, fit these criteria. Defining
a cohort for a Phase II trial in the ovary is more difficult.
This tissue is less accessible for biopsy; consequently, the
presence of precancerous lesions is more difficult to confirm.
The criteria for biomarkers are that they fit expected biological
mechanisms (i.e., differential expression in normal and high-risk
tissue, on or closely linked to the causal pathway for the
cancer, modulated by chemopreventive agents, and short latency
compared with cancer), may be assayed reliably and
quantitatively, measured easily, and correlate to decrease cancer
incidence. They must occur in sufficient incidence to allow their
biological and statistical evaluation relevant to cancer. Since
carcinogenesis is a multipath process, single biomarkers are
difficult to validate as surrogate endpoints, perhaps appearing
on only one or a few of the many possible causal pathways. Panels
of biomarkers, particularly those representing the range of
carcinogenesis pathways, may prove more useful as surrogate
endpoints. It is important to avoid solely on biomarkers that do
not describe cancer but represent isolated events that may or may
not be on the causal pathway or otherwise associated with
carcinogenesis. These include markers of normal cellular
processes that may be increased or expressed during
carcinogenesis. Chemoprevention trials should be designed to
evaluate fully the two or three biomarkers that appear to be the
best models of the cancer. Additional biomarkers should be
considered only if they can be analyzed efficiently and the
sample size allows more important biomarkers to be evaluated
completely. Two types of biomarkers that stand out regarding
their high correlation to cancer and their ability to be
quantified are measures of intraepithelial neoplasia and
indicators of cellular proliferation. Measurements made by
computer-assisted image analysis that are potentially useful as
surrogate endpoint biomarkers include nuclear polymorphism
comprising nuclear size, shape (roundness), and texture (DNA
distribution patterns); nucleolar size and number of
nucleoli/nuclei; DNA ploidy, and proliferation biomarkers such as
S-phase fraction and PCNA...


Shamboul K

Stomal malignant transformation of respiratory papilloma, with
neck metastasis: case report.

Children's National Medical Centre, Washington DC, USA.

Source: East Afr Med J 1996 May;73(5):336-8

Unique Identifier: 96349673


A case of spontaneous malignant transformation at the
mucocutaneous junction of the tracheostomy site in a child with
recurrent respiratory papilloma is presented. A paratracheal neck
metastasis also developed in the same patient in early adulthood.
The respiratory papillomata were first noted at the age of 1.5
years, stomal malignancy at age of seven while the neck mass at
age 14 years. During the prolong course of 13.5 years, the
papillomas were growing aggressively, mainly in the trachea and
main bronchi. Repeated excisions, radiotherapy and a variety of
drugs were tried and discussed. The importance of close
observation and follow-up is stressed. Currently at the age of 16
years, the patient is alive and well and leading normal



Gardner GM; Benninger MS

Adult onset laryngeal papillomatosis.

Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, Detroit, MI 48202, USA.

Source: Ear Nose Throat J 1996 Jul;75(7):404

Unique Identifier: 96334026

[No abstract available]


De Clercq E

Therapeutic potential of Cidofovir (HPMPC, Vistide) for the
treatment of DNA virus (i.e. herpes-, papova-, pox- and
adenovirus) infections.

Rega Institute for Medical Research, Katholieke Universiteit, Leuven.

Source: Verh K Acad Geneeskd Belg 1996;58(1):19-47; discussion 47-9

Unique Identifier: 96269297


(S)-1-(3-Hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC,
Cidofovir, Vistide) is an acyclic nucleoside phosphonate with
broad-spectrum activity against a wide variety of DNA viruses
including herpesviruses [Herpes simplex virus type 1 (HSV-1) and
type 2 (HSV-2), varicella-zoster virus (VZV), cytomegalovirus
(CMV), Epstein-Barr virus (EBV), human herpesvirus type 6 (HHV-6)
and equine and bovine herpesviruses], papovaviruses [human
polyoma virus and human papilloma virus (HPV)], adeno-, irido-,
hepadna-, and poxviruses. HPMPC has proved effective against
these viruses in different cell culture systems and/or animal
models. The mechanism of action of HPMPC is based upon the
interaction of its active intracellular metabolite, the
diphosphorylated HPMPC derivative HPMPCpp, with the viral DNA
polymerase. HPMPCpp has been shown to block CMV DNA synthesis by
DNA chain termination following incorporation of two consecutive
HPMPC molecules at the 3'-end of the DNA chain. HPMPC confers a
prolonged antiviral action, which lasts for several days or
weeks, thus allowing infrequent dosing (i.e. every week or every
two weeks). This prolonged antiviral action is probably due to
the very long intracellular half-life of the HPMPC metabolites,
particularly the HPMPCp-choline adduct. In clinical studies,
HPMPC has proved efficacious in the treatment of CMV retinitis,
following both intravenous injection (3 or 5 mg/kg, every other
week) and intravitreal injection (single dose of 20 micrograms
per eye). Initial clinical trials also point to the efficacy of
both systemic (intravenous) and topical HPMPC (1% ointment) in
the treatment of acyclovir-resistant HSV infections, and of
topical HPMPC (ointment or injection) in the treatment of
pharyngeal, laryngeal and anogenital HPV infections. HPMPC is now
being pursued in the topical and/or systemic (intravenous)
treatment of various infections due to CMV, HSV, VZV, EBV, HPV,
polyoma-, adeno- and poxviruses.



Alvarez Alvarez I; Sanchez Lazo P; Ramos Gonzalez S; Rodrigo Tapia JP; Llorente Pendas JL; Suarez Nieto C

[Simultaneous screening of HPV-6b and 16 in pharyngolaryngeal

Servicio de ORL, Hospital Central de Asturias, Oviedo.

Source: Acta Otorrinolaringol Esp 1996 Mar-Apr;47(2):93-6

Unique Identifier: 96294305


It has been suggested that some human papilloma viruses (HPV) may
play a causal role in cancer of the pharynx, larynx, and oral
cavity, together with factors such as smoking, alcohol, toxins,
and heredity. Using the polymerase chain reaction (PCR), we
detected the two most common genotypes in pharyngolaryngeal
cancer, HPV-6b and 16, in 15 patients from a series of 57 cases.
One patient had both genotypes. The fact that this was the only
positive case in which no other risk factors were present,
particularly alcohol and smoking, suggests that the synergetic
oncogenic action of both viruses could have played an important
role in carcinogenesis.


Toma S; Ragni N; Raffo P; Boselli F; Gustavino C; Rugiati S; Formelli F; Palumbo R; Rosso R; De Cecco L

Efficacy of the association of 13-cis-retinoic acid (13cRA) and
alpha-interferon 2a (alpha-IFN 2a) in moderate-severe cervical
intraepithelial neoplasia (CIN II-III): a pilot study.

National Institute for Cancer Research-IST, Institute of Oncology, University of Genova, Italy.

Source: Anticancer Res 1996 Mar-Apr;16(2):931-6

Unique Identifier: 96275839


Recent in vitro studies have suggested a possible therapeutic
synergism between alpha-IFN 2a and 13cRA in certain neoplasias,
while encouraging in vivo findings strongly support the enhanced
effectiveness of the two agents when used in combination. The
specific aim of our study was to evaluate the efficacy and the
toxicity of the association of 13cRA and alpha-IFN 2a in patients
with CIN II and CIN III who refused surgical treatment.
Twenty-one patients (aged between 25 and 58 years), of which 14
were CIN II and 7 CIN III, entered the study. 13cRA (orally at
0.5-1 mg/Kg/day) and alpha-IFN 2a (intramuscular at 3x10(6)
I.U./day for the first 15 days, then 3 times/week for the
following four weeks) were administered simultaneously for eight
consecutive weeks. 13/21 (62%) histologically verified objective
responses (6 complete and 7 partial) were achieved. We also
obtained 8 stable diseases. Compliance was generally good and no
delays in therapy due to toxicity were recorded (except for two
patients presenting WHO degree III cutaneous and mucosal toxicity
which regressed one week after suspending treatment). Human
Papilloma Virus (HPV) was initially detected in 16/21 (76%)
patients, while HPV negativization after treatment was observed
in 3/16 (19%). Although preliminary and requiring long-term
assessment, the encouraging results of this study confirm the
need for further investigation on the role of systemic medical
therapy in the treatment of CINs.


Rimell FL; Shapiro AM; Mitskavich MT; Modreck P; Post JC; Maisel RH

Pediatric fiberoptic laser rigid bronchoscopy.

Department of Otolaryngology, University of Minnesota Hospitals and Clinics, Minneapolis, 55455 USA.

Source: Otolaryngol Head Neck Surg 1996 Mar;114(3):413-7

Unique Identifier: 96243270


Use of the fiberoptic laser for treatment of tracheobronchial
lesions in the adult is well established. However, there is a
paucity of experience with the fiberoptic laser in the pediatric
airway. Tracheal obstruction caused by granulation tissue or
stenosis, as is often seen in children, may be effectively
treated with this approach. This article documents the successful
use as well as the technologic advantage of the flexible
fiberoptic laser systems, primarily the potassium titanyl
phosphate (KTP) laser, combined with standard pediatric rigid
bronchoscopic equipment in 73 procedures involving 52 children
(43 children younger than five years. with an average age of 21
months). Visualization was excellent, assisted or spontaneous
ventilation was well maintained, and complications were few.


Sakopoulos A; Kesler KA; Weisberger EC; Turrentine MW; Conces DJ Jr

Surgical management of pulmonary carcinoma secondary to recurrent
respiratory papillomatosis.

Department of Surgery, Indiana University School of Medicine, Indianapolis, USA.

Source: Ann Thorac Surg 1995 Dec;60(6):1806-7

Unique Identifier: 96110249


Recurrent respiratory papillomatosis is a rare, but acknowledged,
risk factor for pulmonary squamous cell carcinoma. Although
previous reports suggest a poor prognosis for lung cancer
associated with papillomatosis, we have successfully treated 1
such patient, who presented with three synchronous pulmonary
malignancies, using parenchyma-sparing resection techniques.



Borysiewicz LK; Fiander A; Nimako M; Man S; Wilkinson GW; Westmoreland D; Evans AS; Adams M; Stacey SN; Boursnell ME; Ru

A recombinant vaccinia virus encoding human papillomavirus types
16 and 18, E6 and E7 proteins as immunotherapy for cervical
cancer [see comments]

Department of Medicine, University of Wales College of Medicine, Cardiff, UK.

Source: Lancet 1996 Jun 1;347(9014):1523-7

Comment in: Lancet 1996 Jun 1;347(9014):1498-9

Unique Identifier: 96228135


BACKGROUND: Human papillomavirus (HPV) infection, especially with
type 16 or 18, is associated with cervical cancer. Two HPV
proteins, E6 and E7, are consistently expressed in tumour cells.
The objectives of the study were to examine the clinical and
environmental safety and immunogenicity in the first clinical
trial of a live recombinant vaccinia virus expressing the E6 and
E7 proteins of HPV 16 and 18 (TA-HPV). METHODS: The study was an
open label phase I/II trial in eight patients with late stage
cervical cancer. The patients were vaccinated with a single dose
of TA-HPV and kept in strict isolation to monitor local and
systemic side-effects, environmental spread, and anti-E6/E7
immune responses. FINDINGS: Vaccination resulted in no
significant clinical side-effects and there was no environmental
contamination by live TA-HPV. Each patient mounted an
antivaccinia antibody response and three of the eight patients
developed an HPV-specific antibody response that could be
ascribed to the vaccination. HPV-specific cytotoxic T
lymphocytes, the effector mechanism most likely to be of
therapeutic benefit, were detected in one of three evaluable
patients. INTERPRETATION: Further studies to investigate the use
ot TA-HPV for immunotherapy of cervical cancer are warranted.


Galloway DA

Papillomavirus oncoproteins as vaccine candidates [comment]

Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Source: Lancet 1996 Jun 1;347(9014):1498-9

Comment on: Lancet 1996 Jun 1;347(9014):1523-7

Unique Identifier: 96228124

[No abstract available]


Kpemissi E; Agbere AR; Sossou K

[Laryngeal papillomatosis in children: therapeutic problems
apropos of 39 cases at the Lome University Hospital Center]

Service O.R.L., CHU Tokoin, Lome, Togo.

Source: Rev Laryngol Otol Rhinol (Bord) 1995;116(5):335-8

Unique Identifier: 96238659


The retrospective study about 39 cases of laryngeal
papillomatosis emphasizes the management difficulties due to
slenderness of therapeutical resources, delayed consultations
because of health under education of the community and patients'
discouragement during treatment of such a relapsing disease.
Consequently, tracheostomy was needed immediately (25.64%),
breaking of the voice (48.72%) was noted as well as school
backwardness. The use of laser and interferon in laryngeal
papillomatosis treatment is for the future in Togo.


Kass ES; Hillman RE; Zeitels SM

Vocal fold submucosal infusion technique in phonomicrosurgery.

Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts, USA.

Source: Ann Otol Rhinol Laryngol 1996 May;105(5):341-7

Unique Identifier: 96218975


Phonomicrosurgery is optimized by maximally preserving the vocal
fold's layered microstructure (laminae propriae). The technique
of submucosal infusion of saline and epinephrine into the
superficial lamina propria (SLP) was examined to delineate how,
when, and why it was helpful toward this surgical goal. A
retrospective review revealed that the submucosal infusion
technique was used to enhance the surgery in 75 of 152 vocal fold
procedures that were performed over the last 2 years. The vocal
fold epithelium was noted to be adherent to the vocal ligament in
29 of the 75 cases: 19 from previous surgical scarring, 4 from
cancer, 3 from sulcus vocalis, 2 from chronic hemorrhage, and 1
from radiotherapy. The submucosal infusion technique was most
helpful when the vocal fold epithelium required resection and/or
when extensive dissection in the SLP was necessary. The infusion
enhanced the surgery by vasoconstriction of the microvasculature
in the SLP, which improved visualization during cold-instrument
tangential dissection. Improved visualization facilitated maximal
preservation of the SLP, which is necessary for optimal
pliability of the overlying epithelium. The infusion also
improved the placement of incisions at the perimeter of benign,
premalignant, and malignant lesions, and thereby helped preserve
epithelium uninvolved by the disorder.


Balasubramanian S; Govindasamy S

Inhibitory effect of dietary flavonol quercetin on
7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch

Department of Biochemistry, University of Madras, India.

Source: Carcinogenesis 1996 Apr;17(4):877-9

Unique Identifier: 96202098


The inhibitory effect of dietary supplementation with flavonol
quercetin on 7,12-dimethylbenz[a]anthracene (DMBA)-induced
hamster buccal pouch carcinogenesis was investigated. Dietary
quercetin inhibited the incidence of both papillomas and tumors
induced by DMBA. The fluorescence spectra of papillomas and
tumors showed different prominent maxima and a characteristic
peak around 620-630 nm, which could be attributed to the
accumulation of porphyrin compounds. Further, the fluorescence
intensities at 630 nm (FI630nm) were elevated, whereas the ratio
FI530nm/FI630nm was decreased in DMBA-induced lesions. Quercetin
treatment significantly decreased FI630nm and increased the ratio
FI520nm/FI630nm when compared with DMBA-induced lesions. It is
therefore evident that quercetin has an inhibitory effect on
DMBA-induced carcinogenesis and further studies will throw more
light on its use as a chemopreventive agent against oral cancer.


Puranen M; Yliskoski M; Saarikoski S; Syrjanen K; Syrjanen S

Vertical transmission of human papillomavirus from infected
mothers to their newborn babies and persistence of the virus in

Department of Pathology. University of Kuopio, Finland.

Source: Am J Obstet Gynecol 1996 Feb;174(2):694-9

Unique Identifier: 96191880


OBJECTIVE: The purpose of this study was to determine the
potential for human papillomavirus to be transmitted vertically.
STUDY DESIGN: We started a systematic study of children 0.3 to
11.6 years old born to mothers included in the cohort of 530
women prospectively followed up for genital human papillomavirus
infections in Kuopio since 1981. So far 98 children have been
examined. The examinations included medical history, clinical
examination of the oral cavity and hand warts, and cytologic
samples from the oral mucosa for detection of human
papillomavirus deoxyribonucleic acid with polymerase chain
reaction with subsequent Southern blot hybridization. RESULTS:
Human papillomavirus deoxyribonucleic acid was found in 31 of the
98 (31.6%) oral scrapings. with MY09 and MY11 human
papillomavirus primers, 12 of the 98 were positive for human
papillomavirus deoxyribonucleic acid in the electrophoresis gel
and in subsequent hybridization. Nineteen of the positive samples
were not visible in the gel but become positive when hybridized.
At delivery, 5 mothers had genital human papillomavirus infection
with the same virus type found in her child. In the additional 11
mothers genital human papillomavirus infection with the same
virus type as in the child was diagnosed a few months before or
after delivery. Mothers of the 25 children shown to be negative
for oral human papillomavirus were also human papillomavirus
deoxyribonucleic acid negative at delivery. Minor hyperplastic
growths of the oral mucosa were found in 21 of the 98 children
(21%). One child had a papilloma where human papillomavirus 16
deoxyribonucleic acid was detected, as was also found in her
mother's genital area at delivery. CONCLUSIONS: Our results
support the concept that an infected mother can transmit human
papillomavirus to her child.


Kirnbauer R; Chandrachud LM; O'Neil BW; Wagner ER; Grindlay GJ; Armstrong A; McGarvie GM; Schiller JT; Lowy DR; Campo MS

Virus-like particles of bovine papillomavirus type 4 in
prophylactic and therapeutic immunization.

Division of Immunology, Allergy and Infectious Diseases (DIAID), University of Vienna Medical School, Austria.

Source: Virology 1996 May 1;219(1):37-44

Unique Identifier: 96204570


Virus-like particles were produced in insect cells containing
either the L1 and L2 capsid proteins of bovine papillomavirus
type 4 (BPV-4) or only the L1 protein. Both preparations of VLPs
proved to be extremely effective prophylactic vaccines. Thirteen
of 15 calves immunised with either L1-L2 VLPs or L1-VLPs were
refractory to experimental challenge with high doses of BPV-4 and
did not develop papillomas, while 9 of 10 control animals
developed multiple oral papillomas. VLPs were not efficient as
therapeutic vaccine in calves with established papillomas,
although VLP-vaccinated animals appeared to undergo tumour
regression more rapidly than nonvaccinated control animals.
Antibody responses in VLP-vaccinated calves were associated with
prevention of disease but not with regression of papillomas. Thus
prophylactic VLP vaccination is effective in preventing disease
in this model of mucosal papillomavirus infection. VLPs and
native virus share at least some conformational epitopes, as
shown by the cross-reactivity of their antibodies.


Mao EJ; Schwartz SM; Daling JR; Oda D; Tickman L; Beckmann AM

Human papilloma viruses and p53 mutations in normal pre-malignant
and malignant oral epithelia.

Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.

Source: Int J Cancer 1996 Apr 22;69(2):152-8

Unique Identifier: 96201727


HPV infections have been previously observed in oral cancers, and
inactivation of the p53 gene has been shown to be one of the most
common genetic alterations in human tumors. We examined 179 oral
specimens from 70 individuals with histologic findings of either
normal mucosa (n = 6) or oral disease that ranged from mild
dysplasia to invasive squamous-cell carcinoma (n = 64) to
determine the occurrence of both HPV infection and p53 mutations
and their relationship with several clinical factors. HPV
infection was detected by PCR amplification of viral DNA, and the
presence of p53 mutations was assayed using the single-strand
conformation polymorphism (SSCP)-PCR technique. HPV infection was
found in 31% of individuals with oral disease and was not seen in
healthy individuals. Mutations in exons 5, 6, 7 or 8 of the p53
gene were detected in 37.5% of patients with oral lesions and in
a biopsy from 1 healthy individual who was a heavy smoker.
Approximately one-third of lesions classified as pre-malignant
(dysplasia and carcinoma in situ) and 42% of invasive carcinomas
contained p53 mutations. The majority of these mutations were G:T
transversions located within exons 7 and 8. Tumor tissues from 6
patients with oral lesions were found both to be HPV-16-positive
and to contain p53 mutations; of these, 4 were poorly
differentiated carcinomas that were diagnosed as late-stage
disease. In this study, p53 mutations were detected in the early
stages of cancer development.


Rodrigo Chiner O; Gisbert Aguilar J; Sanchez Alcon MD; Morera Perez C

[Pediatric laryngeal papillomatosis: our experience (three

Servicio de ORL, Hospital, Universitario La Fe, Valencia.

Source: Acta Otorrinolaringol Esp 1995 Sep-Oct;46(5):365-6

Unique Identifier: 96104366


Three cases of juvenile laryngeal papillomatosis were treated at
our hospital between 1984 and 1994. Papillomas were excised in
all patients because of upper airway obstruction. Two were given
alpha interferon as complementary treatment. Two patients are
asymptomatic after years of follow-up and one is still taking
alpha interferon.


Naro~zny W; Mikaszewski B; Stankiewicz C

Benign neoplasms of the larynx.

Department of Otorhinolaryngology, Gdansk School of Medicine, Poland.

Source: Auris Nasus Larynx 1995;22(1):38-42

Unique Identifier: 95408148


In a 45-year period (from 1948 to 1992) 291 patients with
histologically proved benign neoplasms of the larynx were
observed and treated. The most frequently occurring tumors were
papillomas, being 95.2% in whole material. In most cases of
benign tumors of the larynx intralaryngeal excision of the tumor
was used. Clinical data and results of treatment were presented
and discussed.


Bagirova MSh; Korshunova OV; Kafarskaia LI; Minkina GN

[The genital tract microflora in patients with a papillomavirus

Source: Zh Mikrobiol Epidemiol Immunobiol 1995 May-Jun;(3):113-6

Unique Identifier: 95389758


In 70 patients of reproductive age (20-30 years) with the
papilloma virus infection of the uterine neck the microflora of
vaginal contents was studied. The study revealed the specific
diversity of bacteria colonizing the vagina and the uterine neck.
High occurrence of Chlamydia and Gardnerella was established. The
detected dysbiotic disturbances in patients with condylomatosis
of the uterine neck were manifested by a decrease in the
isolation rate of lactobacteria and bifidobacteria and by an
increase in the isolation rate of opportunistic bacteria. The
most pronounced dysbiosis in the microflora of the vagina and the
uterine neck was characteristic of patients with papilloma virus
infection in association with cervical intraepithelial neoplasia
of the III degree.


Feyh J

Photodynamic therapy of head and neck tumors.

Klinik und Poliklinik fur Hals-, Nasen-, Ohrenkranke, Klinikum Grosshadern, Universitat Munchen, Deutschland.

Source: Adv Otorhinolaryngol 1995;49:53-7

Unique Identifier: 95381912

[No abstract available]


Mahnke CG

Laser surgery for laryngeal papillomatosis.

Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel, Germany.

Source: Adv Otorhinolaryngol 1995;49:162-5

Unique Identifier: 95381880


Chiominto A; Giannoni M; Ventura L; Ranieri A

[Epidermoid carcinoma of the oral cavity. Considerations of the
role of the papillomavirus]

Dipartimento di Medicina Sperimentale, Universita degli Studi, L'Aquila.

Source: Minerva Stomatol 1995 Mar;44(3):127-32

Unique Identifier: 95349497


Human papilloma virus (HPV) may have an important role in oral
carcinoma etiology. Our work compares the presence of HPV in the
epithelium of oral mucosa of patients with oral carcinoma with
other factors of risk (smoking, alcohol, chronic mucosal trauma).
We studied 33 patients operated for oral cancer at St. Salvatore
Hospital in l'Aquila, in January-December 1990. The presence of
HPV was proved by a direct valuation of morphological signs
(coilocytosis, nuclear inclusions, etc.) and by
immunohistochemical technique with primary antibodies against
structural virus antigens. Among the 33 patients 19 (57.6%) were
positive for HPV and 14 (42.4%) were negative. Among the HPV
positive subjects 13 were smokers, 11 usually assumed alcohol and
6 had chronic mucosal trauma. Among the HPV negative subjects 9
were smokers, 7 assumed alcohol and 3 had chronic mucosal trauma.
The statistical evaluation of data showed the lack of
significance of viral infection compared to other factors of
risk. In spite of a few cases examined, we suppose that HPV
doesn't play a primary role in oral cancerogenesis, but is a
concomitant cause with other factors of risk.

Backe J; Roos T; Kaesemann H; Martius J; Ott M

[Local therapy and adjuvant interferon therapy in genital
papilloma virus infections]

Universitatsfrauenklinik Wurzburg, Deutschland.

Source: Gynakol Geburtshilfliche Rundsch 1995;35(2):79-84

Unique Identifier: 95345758


OBJECTIVE: Is it possible to reduce the recurrence rates of
HPV-positive genital tract lesions by systemic interferon alfa-2a
in addition to local therapy? METHODS: Thirty-three of 63
patients with first manifestation of papillomavirus infection or
monolocal manifestation were treated by local therapy. The other
30 patients with recurrent or multiorgan infections received 3
courses with 12 x 10(6) IU interferon alfa-2a subcutaneously.
RESULTS: For the remaining 47 patients (16 were lost to
follow-up) we found a significantly lower recurrence rate of 21%
(5 of 24) in the group of interferon-treated patients compared to
52% (12 of 23) of patients treated without interferon.
CONCLUSIONS: The systemic treatment of HPV-positive genital tract
lesions with interferon alfa-2a in addition to CO2 laser surgery
or cone biopsy seems to reduce the recurrence rates of
HPV-positive lesions.


Choo CK; Rorke EA; Eckert RL

Retinoid regulation of cell differentiation in a series of human
papillomavirus type 16-immortalized human cervical epithelial
cell lines.

Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4970.

Source: Carcinogenesis 1995 Feb;16(2):375-81

Unique Identifier: 95163188


Retinoids are important regulators of cervical epithelial cell
differentiation and have been used in the treatment of cervical
cancer. In the present study we evaluate the effects of retinoic
acid on expression of biochemical markers of differentiation and
expression of human papillomavirus reading frames encoding the
early gene products E6 and E7 in normal and HPV16-immortalized
cervical epithelial cell lines. Our results indicate that the
differentiation markers cytokeratins K5 and K16 and
transglutaminase type 1 are suppressed by all-trans-retinoic acid
(RA). A marked concentration-dependent reduction in the level of
of each mRNA is observed with maximal suppression at 1 microM.
Each of the HPV16-immortalized cell lines (ECE16-1, ECE16-D1 and
ECE16-D2) are more sensitive to the effects of RA than normal
cells. The level of HPV16 transcript encoding E6/E7 is not
significantly suppressed by 1 microM RA in ECE16-1 cells, but is
suppressed in ECE16-D1 and ECE16-D2 cells. In addition, an
increase in HPV transcripts encoding E6/E7 is observed at
intermediate (10 and 100 nM) retinoic acid concentrations in
ECE16-1 and ECE16-D2 cells, but not in ECE16-D1 cells. Our
results show that retinoids regulate E6/E7 transcript levels in
some cervical cell lines but not in others, suggesting that
different cervical tumors may respond to retinoids via different


Palefsky JM; Silverman S Jr; Abdel-Salaam M; Daniels TE; Greenspan JS

Association between proliferative verrucous leukoplakia and
infection with human papillomavirus type 16.

Department of Stomatology, School of Dentistry, University of California, San Francisco 94143, USA.

Source: J Oral Pathol Med 1995 May;24(5):193-7

Unique Identifier: 95341559


Proliferative verrucous leukoplakia (PVL) is a recently described
clinical entity characterized by multifocal oral lesions that
frequently progress to oral cancer despite abstinence from
tobacco use by most patients. To determine if this condition is
associated with human papillomavirus (HPV), a polymerase chain
reaction (PCR) for HPV DNA was performed on 9 lesions from 7
patients with PVL, histologically diagnosed with focal keratosis
(1), papilloma (1), epithelial dysplasia (5) and squamous cell
cancer (2). Eight (89%) were HPV positive, 7 for HPV 16. For
comparison, we studied 55 non-PVL-associated oral specimens,
including 24 oral squamous cell cancers. Of the cancers, 8 (33%)
were HPV positive, 4 for HPV 16. These data suggest that HPV 16
infection may play an important role in the pathogenesis of
PVL-associated oral dysplasia and possibly cancer, but is found
in only a small proportion of the more common, non-PVL
associated-oral lesions.


Elo J; Hidvegi J; Bajtai A

Papova viruses and recurrent laryngeal papillomatosis.

Department of Otorhynolaryngology and Pathology, Uzsoki District Hospital, Budapest, Hungary.

Source: Acta Otolaryngol (Stockh) 1995 Mar;115(2):322-5

Unique Identifier: 95335208


The pathogenesis of larynx papillomas has been a challenge of
medical science for a long time. Both clinical observations and
electronmicroscopical examinations have made it possible to
establish the viral origin. Final evidence, however, has been
achieved only by complicated immunohistochemical investigations.
The Papova viruses--types 6 and/or 11--can be detected with in
situ hybridization polymerase chain reaction amplification. HPV
can be positivity demonstrated not only from visible papillomas
but--in significant percentage--in neighboring healthy-looking
mucous membranes. It may reveal the inadequacies of removal of
lesions and the need for adjuvant therapy. To make treatment more
effective we have developed a therapeutic regimen that combines
CO2 laser microsurgery with immunostimulants.

Beck JC; McClatchey KD; Lesperance MM; Esclamado RM; Carey TE; Bradford CR

Presence of human papillomavirus predicts recurrence of inverted

Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor 48109-0312, USA.

Source: Otolaryngol Head Neck Surg 1995 Jul;113(1):49-55

Unique Identifier: 95327353


Recent evidence suggests that human papillomavirus may play a
role in the pathogenesis of inverted papilloma, a benign but
locally aggressive neoplasm with a high recurrence rate and an
association with squamous cell carcinoma. Histologic features of
inverted papilloma have not been useful in discriminating lesions
at high risk for recurrence. We studied archival pathology
specimens from 32 patients with inverted papilloma treated at the
University of Michigan between 1980 and 1994 with polymerase
chain reaction techniques and human papillomavirus E6 and L1
consensus primers. Twenty (63%) specimens tested positive for
human papillomavirus. The clinical status of the remaining 25
patients was reviewed after seven patients with recent diagnosis
or who were lost to follow-up were excluded. A significant
association was identified between the presence of human
papillomavirus DNA in inverted papilloma and recurrence after
surgical excision. Thirteen of 15 patients whose tumors tested
positive for HPV recurred, whereas none of the 10 patients whose
tumors were human papillomavirus negative recurred (p < 0.00002).
This strongly suggests that the presence of human papillomavirus
predicts recurrence of inverted papilloma.


Yoshida T; Saeki T; Ohashi S; Okudaira T; Lee M; Yoshida H; Maruoka H; Ito H; Funasaka S; Kato H

[Clinical study of photodynamic therapy for laryngeal cancer]

Department of Otolaryngology Head and Neck Surgery, Tokyo Medical College.

Source: Nippon Jibiinkoka Gakkai Kaiho 1995 May;98(5):795-804

Unique Identifier: 95325950


Photodynamic therapy (PDT) is an innovative treatment involving
the use of a photosensitizer and low powered laser to selectively
destroy tumor cells. In the head and neck, its application to
laryngeal papilloma, metastatic tumor and oral cancer have been
reported but our report on PDT for laryngeal cancer is the only
clinical report in Japan. At present, we treat laryngeal cancer
by PDT using argon and excimer dye lasers such as the HpD. In the
present study, we assessed the utility and safety of PDT and
investigated long-term prognosis after this therapy. The subjects
were 12 patients with laryngeal cancer who underwent PDT between
February 1988 and October 1993. Among them, ten with cancer of
the vocal cords underwent PDT as the primary treatment and two
underwent PDT because of recurrence after radiotherapy. Under
local anesthesia, PDT was performed using a video endoscope
(Pentax EB2000). The optimal dose from an argon dye laser was set
at 200-500 mW/cm2 of continuous waves for 20 minutes and that
from the excimer dye laser was set at 200 J/cm2 of pulse waves
(3-4 mJ/pulse, 30-40 Hz). The argon dye laser used was the
Fujinon PDT developed by Fuji Photo Optical Co., Ltd. The excimer
dye laser used was a product of Hamamatsu Photonics Co., Ltd. 1)
Effect of PDT The effect of PDT as a primary treatment for ten
patients was classified as CR in eight and PR in two cases, the
CR rate being 80.0%. When evaluated only for T1 patients, the
results were classified as CR in eight and PR in one. The patient
whose response was classified as PR had refused repeated PDT. CR
was maintained for five and 13 months in the two patients who
underwent PDT as a secondary treatment after radiotherapy. CR was
obtained in 83.3% of all patients studied. 2) Duration of the
effect of PDT and long-term prognosis The patients were followed
up for 14 to 71 months. The longest duration of CR achieved by
PDT monotherapy was 65 months. Among the patients who underwent
PDT as a primary treatment, one developed local recurrence and
underwent radiotherapy. However, the prognosis was uneventful in
all other patients. CR after PDT monotherapy was maintained for
42 months in one T3 patient. Two patients with a history of
previous treatment thereafter relapsed and underwent total
laryngectomy. The larynx could be conserved in 83.3% of all
patients. However, it could be conserved in 100% of patients who
underwent PDT as a primary treatment.(ABSTRACT TRUNCATED AT 400


Campo MS

Infection by bovine papillomavirus and prospects for vaccination.

Beatson Institute for Cancer Research, CRC Beatson Laboratories, Glasgow, UK.

Source: Trends Microbiol 1995 Mar;3(3):92-7

Unique Identifier: 95291658


Infection with bovine papillomavirus (BPV) results in the onset
of benign proliferative lesions that usually regress
spontaneously through a cell-mediated immune response.
Occasionally, warts persist as benign tumours or progress to
squamous-cell carcinomas. Vaccines that prevent or cure BPV
infection provide a model for the formulation of vaccines against
human papillomavirus.


Bollag W

Experimental basis of cancer combination chemotherapy with
retinoids, cytokines, 1,25-dihydroxyvitamin D3, and analogs.

F. Hoffmann-La Roche, Ltd., Basel, Switzerland.

Source: J Cell Biochem 1994 Dec;56(4):427-35

Unique Identifier: 95197705


Retinoids, cytokines as well as 1,25-dihydroxyvitamin D3
[1,25(OH)2D3] and analogs possess properties known to contribute
potentially to cancer chemopreventive and chemotherapeutic
effects. They induce cell differentiation, inhibit cell
proliferation, suppress expression of viral oncogenes, and
inhibit angiogenesis necessary for tumor growth. Since clinical
combination chemotherapy of cytotoxic agents has proven superior
to monotherapy, this modality might also be useful for other
classes of antitumor drugs. A series of retinoids, such as
all-trans-, 13-cis-, 9-cis retinoic acid, and acitretin,
cytokines, 1,25(OH)2D3, and analogs have been investigated in
model systems of differentiation, proliferation, viral oncogenes,
and angiogenesis. The three classes of compounds have common
effects but nevertheless show a variance depending on the
particular representative of each class. Combination of compounds
of the different classes led in the various models to a higher
efficacy compared with the compounds given alone. Cytokines such
as IFN alpha, IFN gamma, G-CSF, TNF alpha, IL-1, and IL-4
markedly potentiate the differentiation-inducing effect of
retinoids. Cytokines as well as retinoids combined with
1,25(OH)2D3 and analogs synergistically enhanced differentiation
induction in human transformed hemopoietic cell lines. On a
series of human transformed epithelial cell lines a panel of
cytokines, such as IFN alpha, IFN gamma, TNF alpha, TGF beta, and
EGF acted synergistically with retinoids on inhibition of
proliferation. This was also observed by combining retinoids with
1,25(OH)2D3 and analogs. Retinoids as well as interferons alpha
and gamma have the capacity to suppress the oncogene expression
of human papilloma viruses which are involved in induction and
growth of certain malignancies such as cervical cancer.(ABSTRACT


Akutsu N; Shirasawa H; Nakano K; Tanzawa H; Asano T; Kobayashi S; Isono K; Simizu B

Rare association of human papillomavirus DNA with esophageal
cancer in Japan.

Department of Surgery, School of Medicine, Chiba University, Japan.

Source: J Infect Dis 1995 Feb;171(2):425-8

Unique Identifier: 95146792


To examine whether human papillomavirus (HPV) DNA is associated
with esophageal cancer, frozen and paraffin-embedded neoplasms of
the upper aerodigestive tract, including esophageal cancer, were
investigated. DNA obtained from frozen specimens and cell lines
were analyzed by both polymerase chain reaction (PCR) and
Southern blot hybridization. DNA from paraffin-embedded samples
were analyzed strictly by PCR. DNA of HPV types 6 and 11 was
detected in papillomas of the upper respiratory tract at > 50%.
However, HPV DNA was infrequently detected in specimens from the
upper digestive tract (31 esophageal cancers and 2 esophageal
carcinoma--derived cell lines), even by PCR at a sensitivity of
0.1 copy number per cell. These results suggest that the
etiologic significance of HPV infection in esophageal cancer is



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