RRP Medical Reference Service





An RRP Foundation Publication


edited by


Dave Wunrow and Bill Stern










Summer 1999



Volume 6 Number 2













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 with abstracts from recent (1998 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:
Journal or reference
Language (if it is not specified assume article is in English)
Primary affiliation (when specified)
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
(609) 530-1443 or (609)452-6545
E-mail: bills@rrpf.org

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


RRPF Selected Articles and Abstracts


Laryngoscope 1999 Jul;109(7 Pt 1):1165-6


Use of a laryngeal micro resector system.  [Xomed "Shaver"]

Myer CM 3rd, Willging JP, McMurray S, Cotton RT

Department of Otolaryngology and Maxillofacial Surgery, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.

[No Abstract available at this time]

Unique Identifier: 99328289



Laryngoscope 1999 Jul;109(7 Pt 1):1137-41


Characterization of cyclooxygenase in laryngeal papilloma by molecular techniques

Robinson AB; Das SK; Bruegger DE; Hoover LA; Sanford TR

Department of Otolaryngology-Head and Neck Surgery, University of Kansas Medical Center, Kansas City, USA.

OBJECTIVES: Demonstrate the induction of cyclooxygenase-2 (COX-2) in laryngeal papilloma Discuss the possible causal role of COX-2 in papilloma formation. Consider the potential for treatment of papilloma using selective COX-2 inhibitors. STUDY DESIGN: Molecular biological analysis of COX-1 and COX-2 in laryngeal papilloma. METHODS: Tissue samples from five patients with recurrent respiratory papillomatosis (RRP) were analyzed by in situ hybridization, immunohistochemical staining, and reverse transcription polymerase chain reaction (RT-PCR) techniques. RESULTS: In situ hybridization to COX-2 mRNA showed strong autoradiographic signal surrounding fibrovascular cores. COX-1 autoradiographic signal was low intensity or nondetectable. Normal buccal mucosa biopsies showed low-density or nondetectable autoradiographic signal for both COX-1 and COX-2 mRNAs. In situ hybridization results were corroborated by RT-PCR studies. Levels of COX-2 mRNA were 13-fold more than those in normal mucosa. Immunohistochemical staining for COX-1 and COX-2 showed a similar pattern to that seen with in situ hybridization in both normal and papilloma tissues. CONCLUSIONS: There is an elevation of COX-2 expression in papilloma tissues. This may represent a causal role of COX-2 in the formation and proliferation of laryngeal papilloma. There may also be a role for selective COX-2 inhibition for the treatment of laryngeal papilloma.

Unique Identifier: 99328284



Eur J Dermatol 1998 Oct-Nov;8(7 Suppl):17-9


Imiqimod in clinical practice


Mount Sinai Medical Center, Department of Obstetrics and Gynecology, 1 Mount Sinai Drive, Cleveland, Ohio, USA 44106-4198, USA.

Imiquimod 5% cream is a new compound which modifies the immune response by stimulating the production of interferon alpha and other cytokines. It has shown remarkable promise in the treatment of external genital and perianal warts when applied overnight, three times a week. It is also associated with a lower recurrence than those found with other current treatments. This paper reviews two of the pivotal multi-centre studies which confirm its efficacy in human papilloma virus (HPV) infections. These studies compared the effectiveness and safety of imiquimod 1% cream, imiquimod 5% cream and vehicle cream in the treatment of external anogenital warts.

Unique Identifier: 99319088





Eur J Dermatol 1998 Oct-Nov;8(7 Suppl):13-6


Cytokine induction and modifying the immune response to human papilloma virus with imiquimod

Slade HB

3M Pharmaceuticals, Building 270-3A-01, 3M Center, St Paul, Minnesota, USA.

Imiquimod is the newest in a class of drugs known as immune response modifiers. In preclinical studies, imiquimod induced the production of cytokines - the principal cytokine for antiviral activity being interferon alpha. Imiquimod does not inhibit viruses directly, nor does it cause direct, non-specific cytolytic destruction [1]. Preclinical studies suggest that its antiviral action results from in vivo cytokine- induced activation of the immune system. This paper reviews a recent double blind, placebo-controlled study designed to evaluate this hypothesis. The results of this study showed that wart regression following treatment with imiquimod strongly correlated with a decrease in viral DNA and gene transcripts; a decrease in mRNA expression for proteins associated with cellular proliferation, and an increase in keratinocyte markers. These results support the hypothesis that stimulation of local cytokines by imiquimod leads to a reduction in human papilloma virus (HPV) load; to wart regression and to the normalisation of keratinocyte proliferation without evidence of scarring.

Unique Identifier: 99319087



Eur J Dermatol 1998 Oct-Nov;8(7 Suppl):8-12


The immunology of genital human papilloma virus infection

Stanley M

Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, England.

This paper reports a presentation by Margaret Stanley, Reader in Epithelial Biology, at the University of Cambridge, in which she reviews the evidence to date regarding the immunology of human papilloma virus (HPV) infection in genital warts. In this she explains that investigations into the immunology of genital wart infections indicate that the replication cycle of papilloma viruses is tightly linked to keratinocyte differentiation - a strategy for immune evasion. While the papilloma virus infects primitive basal cells, viral replication and viral assembly are confined to differentiating superficial epithelial cells. Viral replication and release are confined to cells destined for death and are not associated with inflammation. Such findings suggest that the immune system is ignorant or indifferent to the infection. Evidence from regressing genital warts in humans and animal models suggests that HPV is a cell-mediated immune response of the Th1 type offering a strategy for immunotherapy in benign disease. This is supported by evidence from trials with immunomodulatory agents. While strategies to elicit cytotoxic responses are required for malignant HPV associated lesions, the problems of immune evasion associated with these approaches should not be underestimated. Present optimal therapeutic strategies for genital human papilloma viruses infection would therefore appear to require the induction of a virus specific immune response, either by immunomodulatory agents and/or immunization with the relevant viral antigens.

Unique Identifier: 99319086



Eur J Dermatol 1998 Oct-Nov;8(7 Suppl):4


Maw R; Aractingi S

Department of Genitourinary Medicine, The Royal Victoria Hospital, Level 3b, Grosvenor Road, Belfast BT12 6BA, Ireland.

Anogenital warts have become one of the most common sexually transmitted diseases reported in the Western World. The frustration of treatment for both patient and carrier is well recognized. Current available methods rely principally on ablation of visible lesions, with hospital-based treatments often requiring multiple attendance by out- patients. Overall, the current failure rate, recurrence rate, and side- effects of these treatments are highly unsatisfactory. Imiquimod, recently launched in the US under the brand name Aldara trademark cream, represents the most interesting and innovative approach to therapy to become available in many years. Imiquimod is an immune response modifier, therefore this symposium report addresses the vital issues of the immune based response to human papilloma virus (HPV) infection, as well as the problems of persistence caused by HPV disease. The mechanisms by which imiquimod can induce an inflammatory and cell-mediated response are discussed. Also reviewed are the consequent imiquimod clinical results and the reasons why they show great cause for optimism in HPV treatment. As a home-based effective treatment with a low recurrence rate, imiquimod has already generated enthusiasm on an international scale. This symposium report presents the thoughts and experiences of medical specialists from various countries regarding the treatment of genital HPV infections and the place for imiquimod in clinical practice.

Unique Identifier: 99319084



Clin Cancer Res 1999 Jun;5(6):1369-79


Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer

Chen Z; Malhotra PS; Thomas GR; Ondrey FG; Duffey DC; Smith CW; Enamorado I; Yeh NT; Kroog GS; Rudy S; McCullagh L; Mousa S; Quezado M; Herscher LL; Van Waes C

Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland 20892-1419, USA.

Altered immune, inflammatory, and angiogenesis responses are observed in patients with head and neck squamous cell carcinoma (HNSCC), and many of these responses have been linked with aggressive malignant behavior and a decrease in prognosis. In this study, we examined the hypothesis that HNSCC cells produce cytokines that regulate immune, inflammatory, and angiogenesis responses. We identified important regulatory cytokines in supernatants of well-defined and freshly cultured HNSCC cell lines by ELISA and determined whether these cytokines are detected in tumor cell lines and tissue specimens by immunohistochemistry. The serum concentration of the cytokines and cytokine-dependent acute phase inflammatory responses (i.e., fibrinogen, C-reactive protein, and erythrocyte sedimentation rate) from patients with HNSCC was determined, and the potential relationship of serum cytokine levels to tumor volume was analyzed. Cytokines interleukin (IL)-1alpha, IL-6, IL-8, granulocyte-macrophage colony- stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor were detected in similar concentration ranges in the supernatants of a panel of established University of Michigan squamous cell carcinoma (UM-SCC) cell lines and supernatants of freshly isolated primary HNSCC cultures. Evidence for the expression of IL-1alpha, IL-6, IL-8, granulocyte-macrophage colony- stimulating factor, and VEGF in HNSCC cells within tumor specimens in situ was obtained by immunohistochemistry. In a prospective comparison of the cytokine level and cytokine-inducible acute-phase proteins in serum, we report that cytokines IL-6, IL-8, and VEGF were detected at higher concentrations in the serum of patients with HNSCC compared with patients with laryngeal papilloma or age-matched control subjects (at P < 0.05). The serum concentrations of IL-8 and VEGF were found to be weakly correlated with large primary tumor volume (R2 =3D 0.2 and 0.4, respectively). Elevated IL-1- and IL-6-inducible acute-phase responses were also detected in cancer patients but not in patients with papilloma or control subjects (at P < 0.05). We therefore conclude that cytokines important in proinflammatory and proangiogenic responses are detectable in cell lines, tissue specimens, and serum from patients with HNSCC. These cytokines may increase the pathogenicity of HNSCC and prove useful as biomarkers or targets for therapy.

Unique Identifier: 99316783



Anticancer Res 1999 Mar-Apr;19(2B):1391-5


Human papilloma virus DNA detection in oral lesions in the Greek population.

Aggelopoulou EP; Skarlos D; Papadimitriou C; Kittas C; Troungos C

Medical School of Athens, Department of Histology-Embryology, Greece.

HPVs (Human Papilloma Viruses) are small DNA "epitheliotropic" viruses, implicated in cervical carcinogenesis, particularly the "high-oncogenic- risk" types HPV-16 and HPV-18. Data concerning oral carcinogenesis are however, contradictory. We examined the presence of HPV and subsequently HPV-16 and HPV-18 in 102 specimens of paraffin-embedded oral tissue blocks--81 oral squamous cell carcinomas and 21 oral hyperplasias--using PCR technique followed by agarose gel electrophoresis. Our results demonstrated that 49% (50/102) of the samples were HPV positive. Subsequent analysis of HPV positive lesions revealed 22% positivity for HPV-16 and 44% for HPV-18. HPV-18 was detected only in carcinomas, while HPV-16 was more abundant in papillomatous hyperplasias and in a small percentage of carcinomas. These findings may probably indicate a contributing role for HPV-18 as a potent co-carcinogen in oral epithelial carcinogenesis in the Greek population.

Unique Identifier: 99293445



Am J Otolaryngol 1999 May-Jun;20(3):180-3


Irradiation of recurrent respiratory papillomatosis causing spinal cord compression.

Shelton CH; Levine PA; Crane CH; Rich TA

Department of Radiation Oncology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.

[No abstract available.]

Unique Identifier: 99256688



J Am Acad Dermatol 1999 May;40(5 Pt 2):818-21


Resolution of recalcitrant hand warts in an HIV-infected patient treated with potent antiretroviral therapy.

Spach DH; Colven R

Department of Medicine, University of Washington, Seattle, USA. spach@u.washington.edu

Human papilloma virus (HPV)-related cutaneous manifestations occur with increased frequency and severity among HIV-infected persons. In this report, we describe an HIV-infected man with persistent, severe cutaneous hand warts that did not respond to multiple therapies, including liquid nitrogen cryotherapy, topical dinitrochlorobenzene, topical podophyllin, and intralesional interferon-alfa injections. Approximately 1 year after starting a potent protease inhibitor- containing antiretroviral regimen, the patient's recalcitrant cutaneous warts markedly diminished in size, even though the patient did not receive any specific therapy for the warts after starting aggressive antiretroviral therapy. The patient continued on a potent protease inhibitor-containing antiretroviral regimen and, approximately 2 years later, the warts completely resolved. Our patient's dramatic clinical improvement of cutaneous HPV infection that followed protease inhibitor- containing antiretroviral therapy provides a clear-cut example that protease inhibitor-containing combination antiretroviral therapy can produce significant clinical benefit.

Unique Identifier: 99253541



Cancer Res 1999 May 1;59(9):2050-4


Genetic deletion of p21WAF1 enhances papilloma formation but not malignant conversion in experimental mouse skin carcinogenesis.

Weinberg WC; Fernandez-Salas E; Morgan DL; Shalizi A; Mirosh E; Stanulis E; Deng C; Hennings H; Yuspa SH

Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892-4340, USA. wweinberg@yoda.nidr.nih.gov

Tumor suppression by p53 is believed to reside in its ability to regulate gene transcription, including up-regulation of p21WAF1. In p53(-/-) mice, chemical- or oncogene-induced skin tumors undergo accelerated malignant conversion. To determine the contribution of the p21WAF1 gene product to epidermal carcinogenesis, animals +/+, +/-, and -/- for a null mutation in the p21WAF1 gene were treated once with 25 nmol 7,12-dimethylbenz[a]anthracene, followed by 5 microg of TPA two times/week for 20 weeks. Papilloma frequency was higher in the p21WAF1- deficient mice. However, the frequency of malignant conversion was similar among all three genotypes. After TPA treatment, all genotypes developed epidermal hyperplasia, although the labeling index was lower in p21WAF1 (-/-) epidermis compared with p21WAF1 (+/+). Furthermore, the expression of differentiation markers was the same across genotypes in untreated or TPA-treated epidermis. Similar frequencies of malignant conversion were also observed in an in vitro assay. Thus, p21WAF1 suppresses early stages of papilloma formation but not malignant progression in mouse skin carcinogenesis, and decreased levels of p21WAF1 do not account for the enhanced malignant conversion of p53 null epidermal tumors.

Unique Identifier: 99247545



Otolaryngol Head Neck Surg 1999 May;120(5):698-705


High-risk human papillomavirus types and squamous cell carcinoma in patients with respiratory papillomas.

Moore CE; Wiatrak BJ; McClatchey KD; Koopmann CF; Thomas GR; Bradford CR; Carey TE

Department of Otolaryngology, Emory Health System and Grady Memorial Hospital, Atlanta, GA 30335, USA.

Respiratory papillomas (RPs) are benign, virally induced tumors of the larynx and respiratory epithelium that may obstruct the airway and tend to recur frequently. RPs are thought to be the result of infection with the human papillomaviruses (HPVs) types 6 and 11. We surveyed archival RP specimens to determine whether there were correlations of HPV type with patient characteristics or clinical course. Paraffin-embedded papilloma specimens of 45 different patients were analyzed. We assessed HPV types using the polymerase chain reaction with E6 consensus primers, hybrid capture assays (high or low risk), and dot blot hybridization of generic E6 PCR products with E6 type-specific oligonucleotide probes. The presence and type of HPV were correlated with patient data from a retrospective chart review. We found that RPs may have either low- or high-risk HPV types and some contain multiple HPV types. Respiratory infection with high-risk HPV apparently introduces a long-term risk of squamous cell carcinoma development, even in the absence of conventional cofactors. Low-risk HPV infection may also act in association with these cofactors to promote carcinogenesis. Our data also show a racial imbalance in RP that may indicate a difference in genetic resistance and/or susceptibility to HPV infection and the development of RP.

Unique Identifier: 99246441



Anticancer Res 1999 Jan-Feb;19(1A):1-6


Prevalence of human papilloma virus DNA in head and neck cancers carrying wild-type or mutant p53 tumor suppressor genes.

Adams V; Schmid S; Zariwala M; Schmid M; Kleihues P; Briner J; Schafer R

Institute of Clinical Pathology, University Hospital of Zurich, Switzerland.

The normal function of the p53 tumor suppressor protein can be perturbed by non-mutational mechanisms. The E6 protein encoded by high-risk strains of human papilloma virus (HPV) targets the p53 protein resulting in enhanced degradation via the ubiquitin pathway. We have used nested PCR for detecting the presence of HPV DNA in 58 primary head and neck tumors and 15 metastatic lymph nodes, which had been prescreened for p53 mutations in exons 5 to 8. HPV DNA sequences were detected in 12 tumors (20.6%) and 4 metastatic lymph nodes (21%). HPV type 16 DNA was predominantly found in tumors (n =3D 11) and lymph nodes (n =3D 4), one tumor was positive for HPV type 18 sequences. Five of 12 HPV-positive tumors (41%) carried a p53 mutation. Of 46 HPV-negative tumors, 16 (34.8%) carried a p53 mutation. Thus, HPV positivity and p53 mutations were not mutually exclusive in head-and-neck cancer. Three of 6 normal tissues adjacent to the tumor were positive for HPV type 16, while no viral DNA was found in the corresponding tumors. Thus, the presence of HPV type 16 DNA did not directly confer a growth advantage on the population of emerging tumor cells. Instead

Unique Identifier: 99243104



J Voice 1999 Mar;13(1):123-7


Phonomicrosurgical resection of glottal papillomatosis.

Zeitels SM; Sataloff RT

Department of Otology and Laryngology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston 02114, USA.

Controlled debulking has been the surgical approach to treat laryngeal papillomatosis for over a century despite dramatic improvements in surgical technology. It is commonplace to leave disease in the glottis at the end of the procedure (eg, in the anterior commissure) because of complications associated with attempted complete removal. This study examined the recurrence patterns of adult glottal papillomatosis after phonomicrosurgical microflap resection. Between 1990 and 1995, 22 patients underwent phonomicrosurgical resection of glottal papillomatosis. Six patients had not undergone previous microlaryngeal surgery and 16 patients had had prior procedures. All patients underwent resection of all visible papillomatosis, and this frequently required staged resections. The subepithelial infusion technique was used to facilitate the resection in most cases. No patient who underwent resection for primary disease had a recurrence. Ten of 16 (62%) patients who presented with recurrent disease did not have a recurrence after microflap resection. Follow up on all patients was at least 2 years. This preliminary report suggests that recently developed phonomicrosurgical microflap resection techniques can eradicate adult glottal papillomatosis in some cases, and that resection of papillomatosis appears to be preferable to conventional debulking and/or ablation

Unique Identifier: 99238196



Biol Chem 1999 Mar;380(3):335-40


Induction of HPV16 capsid protein-specific human T cell responses by virus-like particles.

Rudolf MP; Nieland JD; DaSilva DM; Velders MP; Muller M; Greenstone HL; Schiller JT; Kast WM

Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University of Chicago, Maywood, IL 60153, USA.

It has been postulated that upon binding to a cell surface receptor, papilloma virus-like particles (VLPs) gain entry into the cytosol of infected cells and the capsid proteins L1 and L2 can be processed in the MHC class I presentation pathway. Vaccination of mice with human papilloma virus-like particles consisting of capsid proteins L1 and L2 induced a CD8-mediated and perforin dependent protective immune response against a tumor challenge with human papilloma virus transformed tumor cells, which express only minute amounts of L1 protein. Here we show that HPV16 capsid proteins stimulate a MHC class I restricted CTL response with human peripheral blood lymphocytes (PBL) in vitro. The vigorous response was specific for VLP-infected target cells and was MHC class I restricted. Moreover we show the presence of at least one HLA-A*0201 restricted CTL epitope within the HPV-16 capsid proteins by using a VLP-'infected' HLA-A*0201 transfected human cell line as target cells. These results demonstrated that VLPs can induce a HPV16 capsid protein-specific immune response in humans, allowing the monitoring of immune responses induced by vaccines based on chimeric VLPs carrying additional immunogenic peptides or proteins in therapeutical applications in human patients.

Unique Identifier: 99237847



Eur J Clin Microbiol Infect Dis. 1999 Feb;18(2):126-32.


Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up.

Baay MF; Duk JM; Burger MP; de Bruijn HW; Stolz E; Herbrink P

Department of Medical Oncology, University of Antwerp, Belgium.

To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the polymerase chain reaction were tested using in vitro translated proteins E6 and E7 in a radioimmunoprecipitation assay and in an E7 synthetic peptide enzyme immunoassay. Antibody levels against E6 and E7 as measured by radioimmunoprecipitation assay showed a nearly identical pattern. Seronegative patients remained seronegative throughout treatment and follow-up. Seropositive patients showed either a decrease in antibody level or stable antibody levels during treatment. In contrast to patients without evidence of disease at the end of the study, the majority of patients with recurrent disease showed increasing antibody levels during the follow-up period. These results indicate that, in patients who are seropositive before treatment antibody levels against E6 and E7 of human papillomavirus type 16 after treatment are closely linked to treatment response. The use of the more sensitive radioimmunoprecipitation assay did not lead to a better correlation of antibody levels with clinical disease status of the patients than the use of the enzyme immunoassay.

Unique Identifier: 99236317



Cancer Lett 1999 Feb 8;136(1):67-74


The inhibitory effects of bryostatin 1 administration on the growth of rabbit papillomas.

Bodily JM; Hoopes DJ; Roeder BL; Gilbert SG; Pettit GR; Herald CL; Rollins DN; Robison RA

Department of Microbiology, Brigham Young University, Provo, UT 84602- 5133, USA.

Bryostatin 1 is a protein kinase C modulator that shows antineoplastic activity in a variety of tumor systems. This study examined the effects of bryostatin 1 administration on papilloma growth in rabbits. Investigations of optimal route, dose, and schedule were performed. Several groups of rabbits were inoculated with cottontail rabbit papillomavirus (CRPV) DNA. Bryostatin 1 was administered i.v., both daily and weekly, and intralesionally both weekly and bi-weekly. Intralesionally dosed papillomas were examined histologically for immune cell infiltration. In weekly and daily i.v. trials, 2.5 and 1.0 microg/kg, respectively, showed the greatest overall reduction in tumor size. Bryostatin 1 administered intralesionally also slowed papilloma growth. Treated lesions had significantly higher numbers of heterophils and eosinophils.

Unique Identifier: 99226923



J Clin Laser Med Surg 1998 Dec;16(6):299-304


Nd:YAG and CO2 laser therapy of oral mucosal lesions.

White JM; Chaudhry SI; Kudler JJ; Sekandari N; Schoelch ML; Silverman S Jr

Department of Restorative Dentistry, School of Dentistry, University of California, San Francisco, USA.

OBJECTIVE: Experiences gained in the management of oral mucosal lesions by CO2 and Nd:YAG laser therapy in an outpatient clinic treated over an 80-year period are described. SUMMARY BACKGROUND DATA: Lasers have indications for use in dentistry for incision, excision, and coagulation of intraoral soft tissue. Advances in laser technology have provided delivery systems for site-specific delivery of laser energy with short interaction items on tissue to be ablated. This study retrospectively evaluates a series of clinical case studies. METHODS: Sixty-four patients with a variety of benign oral soft tissue lesions were treated by laser excision. Thirty-five patients were treated by a pulsed fiberoptic delivered Nd:YAG contact laser, and 29 by a continuous free-beam CO2 non-contact laser. The largest group of lesions treated were leukoplakia (39 cases). Other lesions excised and biopsied were lichen planus, squamous papilloma, pyogenic granuloma, focal melanosis, nonhealing traumatic ulceration, hemangioma, and lymphangioma. All patients were followed postoperatively (mean 6.8 months, range 1-36 months). RESULTS: Laser excision was well tolerated by patients with no intraoperative or postoperative adverse effects. All patients healed postsurgically with no loss of function. CONCLUSIONS: CO2 and Nd:YAG lasers are successful surgical options when performing excision of benign intraoral lesions. Advantages of laser therapy include minimal postoperative pain, conservative site-specific minimally invasive surgeries, and elimination of need for sutures.

Unique Identifier: 99220664



J Laryngol Otol. 1998 Nov;112(11):1101-4.


An aggressive and invasive growth of juvenile papillomas involving the total respiratory tract.

Petersen BL; Buchwald C; Gerstoft J; Bretlau P; Lindeberg H

Department of Pathology, Rigshospitalet, Denmark. RH02875@RH.DK

A malignant course of juvenile laryngeal papillomatosis has rarely been reported. In the present case the patient had had laryngeal papillomas since the age of three years. The papillomas gradually spread to the entire respiratory system, and during 30 years the patient was operated on more than 80 times. At present an invasive tumour spreading from the tongue into the parapharyngeal space, extending to the cranial base, has been demonstrated by magnetic resonance imaging (MRI). Intralesional therapy with Cidofovir, a promising antiviral drug against human papillomavirus (HPV) infection, was started with some clinical effect, although only on the superficial tumour growth. Histology of removed tumour tissue has demonstrated a mixture of exophytic and inverted growth pattern, and has mainly been interpreted as benign, in spite of a focally high mitotic index and an intermittent lack of maturation in the epithelium. In the most recent biopsies a verrucous carcinoma has been diagnosed. Expression of p53 was noted to increase in papillomas with time. All samples have been shown to harbour HPV 11, but no other HPV types.

Unique Identifier: 99212906



Vaccine. 1999 Mar 17;17(11-12):1558-66.


Intramuscular injection of plasmid DNA encoding cottontail rabbit papillomavirus E1, E2, E6 and E7 induces T cell-mediated but not humoral immune responses in rabbits.

Han R; Reed CA; Cladel NM; Christensen ND

Jake Gittlen Cancer Research Institute, Department of Pathology, Pennsylvania State University College of Medicine, Hershey 17033, USA.

To test the efficacy of genetic vaccination against papillomavirus infection, plasmid DNA encoding cottontail rabbit papillomavirus (CRPV) E1, E2, E6, E7 or without insert were intramuscularly injected into five groups of rabbits. Peripheral blood mononuclear cells (PBMCs) showed specific proliferation upon in vitro stimulation with E1, E2, E6 or E7 proteins in a majority of vaccinated rabbits but Western blot analysis did not detect antibodies specific for these viral proteins in rabbit serum. All rabbits grew papillomas after virus challenge and none of the rabbits showed systemic papilloma regression. These observations showed that intramuscular injection of plasmid DNA encoding CRPV E1, E2, E6 or E7 induced CD4+ T cell-mediated but not humoral immune responses, and did not result in the protection of rabbits from virus infection.

Unique Identifier: 99210168



J Gen Virol 1999 Mar;80 ( Pt 3):595-600


Human papillomavirus type 16 variant lineages characterized by nucleotide sequence analysis of the E5 coding segment and the E2 hinge region.

Eriksson A; Herron JR; Yamada T; Wheeler CM

University of New Mexico, School of Medicine, Health Sciences Center, Department of Molecular Genetics and Microbiology, Albuquerque 87131- 5276, USA.

We have previously examined 29 cervical cell isolates for human papillomavirus type 16 (HPV-16) sequence variations in the E6, L2 and L1 coding regions, and the long control region (LCR). Twenty-five of these isolates as well as 23 additional isolates are characterized here as we present the complete E5 coding segment and the E2 hinge region. Eight amino acid variations were observed in the E5 coding segment, 13 were identified in the E2 hinge region and 5 were observed in the overlapping E4 coding segment. These amino acid variations may be relevant to differences in biological functions and may result in altered humoral or cell-mediated immune responses to HPV-16 variants. The characterization of sequence variation within high-risk HPV types might be important in the search for epidemiological correlates of cervical cancer risk. This work complements and extends HPV-16 genome sequence information from specific isolates previously reported by our group.

Unique Identifier: 99190418



Ear Nose Throat J. 1999 Feb;78(2):82-3.


Recurrent invasive papilloma of the vocal fold.

Sataloff RT; Spiegel JR; Hawkshaw M

Thomas Jefferson University, USA.

[No abstract available.]

Unique Identifier: 99189560



Hum Pathol. 1999 Mar;30(3):274-83.


Human papilloma virus (HPV) is possibly involved in laryngeal but not in lung carcinogenesis.

Gorgoulis VG; Zacharatos P; Kotsinas A; Kyroudi A; Rassidakis AN; Ikonomopoulos JA; Barbatis C; Herrington CS; Kittas C

Department of Histology and Embryology, School of Medicine, University of Athens, Greece.

Data on human papilloma virus (HPV) involvement in preneoplastic and neoplastic lesions of the larynx and lung are limited and conflicting. The presence of HPV was investigated in a series of laryngeal specimens and non-small cell lung carcinomas (NSCLCs). The laryngeal samples (154) comprised 14 cases with hyperplasia without dysplasia, 49 with dysplasia, and 91 squamous cell carcinomas (SqCCs). The NSCLCs included 31 SqCCs, 32 adenocarcinomas, and 5 undifferentiated large cell carcinomas. Furthermore, we examined, for HPV DNA sequences, 14 bronchial metaplastic squamous lesions located next to cancerous areas. We used a sensitive nested polymerase chain reaction assay (NPCR), dot blotting, and in situ hybridization. The findings were correlated with clinicopathologic features of the patients. In the laryngeal specimens, NPCR analysis showed HPV DNA in 20 (13%) of the 154 specimens. Notably, 19 of 20 HPV-positive cases were carcinomas and only one was a mild dysplastic lesion. Typing of the carcinomas showed single HPV 6, 16, 18, and 33 infection in 1 (1.1%), 12 (13.2%), 2 (2.2%), and 1 (1.1%) samples, respectively, and HPV 6/33, 16/33, and 6/18 coinfection in three carcinomas. In situ hybridization findings were in agreement with PCR results, with the exception of two cases in which HPV 18 DNA was detected only by PCR. HPV was more frequently observed in heavy smokers than in patients with low daily cigarette consumption and nonsmokers (P =3D .03). There was no correlation between virus infection and gender, grade, and lymph node status of the carcinomas. None of the NSCLCs or adjacent metaplastic squamous epithelium contained HPV DNA sequences. The presented data suggest a contributory role of HPV in late stages of laryngeal carcinogenesis, because all premalignant lesions were negative but one. This study does not support a potential role of HPV in the development of NSCLCs.

Unique Identifier: 99186406



Orv Hetil. 1999 Feb 21;140(8):405-9. Review. Hungarian.


Virologic aspects of juvenile laryngeal papillomatosis

Major T; Jokay I; Soos G; Gergely L; Czegledy J

Juvenile laryngeal papillomatosis is the most common benign tumor of the larynx in childhood. The specific etiological factors are non- oncogenic human papillomavirus types 6 and 11. In the present study two cases (a 6-year-old male and a 5 and a half-year-old female) operated five times each and harbouring type 11 DNA in papillomas excised in the first operations are analysed from the following virological aspects: 1. the examination of vertical transmission by general primer- polymerase chain reaction of maternal cervical exfoliation; 2. sites of papilloma predilections in the larynx; 3. histopathology; 4. viral DNA detection from the formalin-fixed and paraffin-embedded archive tissues and from a fresh papilloma tissue in one case by polymerase chain reaction applying type-specific primers. We did not find any signs of maternofoetal transmission in the anamnesis and the maternal cervix proved to be negative for viral DNA. However, the vertical route of transmission can not be excluded due to the special natural history of papillomavirus infections. Papillomas usually localised in normal squamociliary junctions of the larynx. The histopathologic review did not reveal any signs of malignancy. Koilocytosis referring to productive viral infection and the signs of abnormal keratinisation were present in each tissue. All tissues of the patients proved to be positive for the short amplimer deriving from the genome of human papillomavirus type 11.

Unique Identifier: 99183382



Vestn Otorinolaringol. 1998;(6):28-9. Russian.


Congenital juvenile respiratory papillomatosis of the larynx

Bogomil'skii MR; Soldatskii IuL; Maslova IV; Nurmukhametov RKh

The data obtained by foreign and national investigators on pathogenesis of congenital juvenile papillomatosis allow to confirm the existence of a congenital form of juvenile respiratory papillomatosis of the larynx.

Unique Identifier: 99181237



Cancer Res. 1999 Feb 15;59(4):968-74.


Elevation of the epidermal growth factor receptor and dependent signaling in human papillomavirus-infected laryngeal papillomas.

Johnston D; Hall H; DiLorenzo TP; Steinberg BM

Department of Otolaryngology, Long Island Jewish Medical Center, The Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, New York 11040, USA.

Laryngeal papillomas are benign tumors caused by human papillomaviruses types 6 and 11. This study addressed alterations in levels of signal transduction from the epidermal growth factor receptor (EGFR) in papillomas and cultured papilloma cells compared to normal tissue and cells. Mitogen-activated protein kinase (MAPK) was activated to a greater extent, phosphotyrosine was more abundant, and EGFR was overexpressed in laryngeal papillomas compared to normal laryngeal epithelium by Western blot analysis. The EGFR was 3 times more abundant in cultured papilloma cells than in normal laryngeal cells by Scatchard analysis and Western blot, without gene amplification or an increase in steady-state levels of mRNA. Following stimulation with EGF, a significant portion of the EGFR was recycled to the surface in papilloma cells, whereas in normal cells, it was not. Tyrosine kinase activity and activation of MAPK was more responsive to epidermal growth factor stimulation in papilloma cells than in uninfected primary laryngeal cells. PD153035, a specific inhibitor of the EGFR, and an EGFR-specific antibody that blocks ligand binding completely abrogated basal MAPK activation by endogenous ligands in laryngeal papilloma cells. These results demonstrated that infection of laryngeal epithelium by low-risk human papillomaviruses elevates the EGFR by posttranslational mechanisms, increasing its responsiveness to ligand- mediated activation. They also showed that MAPK activation in laryngeal papillomas depends upon ligand-mediated EGFR stimulation.

Unique Identifier: 99151550



Oral Oncol. 1998 Nov;34(6):448-53. Review.


Molecular piracy: the viral link to carcinogenesis.

Flaitz CM; Hicks MJ

Department of Stomatology, University of Texas, Houston Health Science Center 77030, USA.

The vast majority of the human experience with viral infections is associated with acute symptoms, such as malaise, fever, chills, rhinitis and diarrhea. With this acute or lytic phase, the immune system mounts a response and eliminates the viral agent while acquiring antibodies to that specific viral subtype. With latent or chronic infections, the viral agent becomes incorporated into the human genome. Viral agents capable of integration into the host's genetic material are particularly dangerous and may commandeer the host's ability to regulate normal cell growth and proliferation. The oncogenic viruses may immortalize the host cell, and facilitate malignant transformation. Cell growth and proliferation may be enhanced by viral interference with tumor suppressor gene function (p53 and pRb). Viruses may act as vectors for mutated proto-oncogenes (oncogenes). Overexpression of these oncogenes in viral-infected cells interferes with normal cell function and allows unregulated cell growth and proliferation, which may lead to malignant transformation and tumour formation. Development of oral neoplasms, both benign and malignant, has been linked to several viruses. Epstein-Barr virus is associated with oral hairy leukoplakia, lymphoproliferative disease, lymphoepithelial carcinoma, B- cell lymphomas, and nasopharyngeal carcinoma. Human herpesvirus-8 has been implicated in all forms of Kaposi's sarcoma, primary effusion lymphomas, multiple myeloma, angioimmunoblastic lymphadenopathy, and Castleman's disease. Human herpesvirus-6 has been detected in lymphoproliferative disease, lymphomas, Hodgkin's disease, and oral squamous cell carcinoma. The role of human papillomavirus in benign (squamous papilloma, focal epithelial hyperplasia, condyloma acuminatum, verruca vulgaris), premalignant (oral epithelial dysplasia), and malignant (squamous cell carcinoma) neoplasms within the oral cavity is well recognized. Herpes simplex virus may participate as a cofactor in oral squamous cell carcinoma development by enhancing activation, amplification, and overexpression of pre- existing oncogenes within neoplastic tissues. Because of the integral role of viruses in malignant transformation of host cells, innovative antiviral therapy may prevent tumour development, involute neoplastic proliferations, or arrest malignant progression.

Unique Identifier: 99129215



Laryngoscope. 1999 Jan;109(1):21-6.


Relationship of human papillomavirus to Schneiderian papillomas.

Weiner JS; Sherris D; Kasperbauer J; Lewis J; Li H; Persing D

Department of Otorhinolaryngology, Mayo Clinic, Rochester, Minnesota 55905, USA.

OBJECTIVES/HYPOTHESIS: To classify a large group of Schneiderian papillomas (SPs) into their histologic subtypes and to determine the incidence of human papillomavirus (HPV) in each subtype. STUDY DESIGN: Pathologic review and polymerase chain reaction-based (PCR-based) examination of archived tissue. METHODS: Slides of 114 tumors diagnosed as Schneiderian, inverting, fungiform, or cylindric cell papillomas, or any associated carcinomas, were examined by a head and neck pathologist. Using PCR, consensus primers for the L1 region of HPV were used to determine the presence of HPV in the tumors. This was also performed on normal turbinate control specimens. RESULTS: Eighty-two (78%) were the inverting subtype, 21 (20%) the fungiform subtype, and 2 (2%) the cylindric cell type. Nine tumors were diagnosed as either verrucous or squamous cell carcinoma. Eighty-eight percent of the tumors had DNA of sufficient quality to be amplified using PCR. Of these, 5 of 69 (6.8%) inverting, 17 of 17 (100%) fungiform, and 0 of 2 cylindric cell papillomas were positive for HPV. One of nine (11.1%) cancers was positive for HPV. No normal turbinate tissue contained HPV. HPV types 6b and 11 accounted for all cases of fungiform papillomas. Of the five HPV-positive inverting papillomas, three had HPV type 11 and two had HPV type 16. The single carcinoma containing HPV contained HPV type 18. CONCLUSIONS: The histologic subtype of SPs is important, as their etiologies appear to be different. HPV 6b and 11 appear to be involved in all cases of fungiform papillomas but are only rarely involved in cases of inverting or cylindric cell papillomas. HPV 16 may rarely play a role in cases of inverting papillomas, and HPV 16 and 18 may be involved in a subset of cases of carcinomas originating in an inverting papilloma.

Unique Identifier: 99114072



Anticancer Res. 1998 Nov-Dec;18(6B):4765-8.


Human papilloma virus (HPV) type 16 and 18 detected in head and neck squamous cell carcinoma.

Mineta H; Ogino T; Amano HM; Ohkawa Y; Araki K; Takebayashi S; Miura K

Department of Otolaryngology, Hamamatsu University School of Medicine, Japan.

BACKGROUND: Recently the HPV genome has been detected in 75-80% of uterine cervical squamous cell carcinomas. High-risk HPV 16,18,31,33, and 45 are frequently associated with invasive carcinoma of the oral cavity, oropharynx, larynx, and nasal cavity. In this study we investigated the association of HPV16 and 18 in head and neck squamous cell carcinomas (HNSCC) using PCR-based methods. MATERIALS AND METHODS: Ninety-eight fresh frozen tissues from HNSCC were collected. The samples were consisted of 26 cases from the larynx, 19 from the nasal and paranasal sinus, 16 the hypopharynx, 14 the oral cavity, 13 the oropharynx, and 10 from the nasopharynx. The presence of HPV genome was examined by PCR using HPV16 and 18 specific primers encoding E7 ORF. RESULTS: HPV16-DNA was detected in 23% of all cases (23/98), 31% (8/26) larynx, 16% (3/19) nasal and paranasal sinus, 19% (3/16) hypopharynx, 21% (3/14) oral cavity, 38% (5/13) oropharynx, and 10% (1/10) nasopharynx. HPV18-DNA was detected in 4% of all cases (4/98), 8% (2/26) larynx, and 15% (2/13) oropharynx. 54% (7/13) in oropharynx and 38% (10/26) in larynx showed rather high prevalence in the head and neck. CONCLUSIONS: HPV 16 and 18 play an important role in carcinogenesis of the head and neck, especially, in the oropharynx and larynx.

Unique Identifier: 99108703



Anticancer Res. 1998 Nov-Dec;18(6B):4569-73.


Estrogen metabolism and laryngeal papillomatosis: a pilot study on dietary prevention.

Auborn K; Abramson A; Bradlow HL; Sepkovic D; Mullooly V

Department of Otolaryngology, Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA. auborn@aecom.yu.edu

Evidence exists that estrogen metabolism has a role in the pathogenesis of recurrent respiratory papillomatosis (RRP). This disease has a papillomavirus etiology and is characterized by recurrent benign tumors with a significant propensity to become malignant. We have measured the systemic transformation of estrogen using an enzyme-linked-immunoassay to measure estrogen metabolites in the urine of patients with RRP and compared these ratios to the severity of RRP, a measure of the average growth rate of papillomas. Our results show an inverse relationship between the ratio of C-2 to C-16 alpha-hydroxylated estrogens and the severity of RRP. In a pilot study, patients consumed cruciferous vegetables to induce C-2-hydroxylation. In this group of patients, an increase in the ratio correlated with an improvement in RRP. The ratio did not change in a subset of these patients, and their RRP did not improve. Regardless, the ratio correlated with severity of their RRP.

Unique Identifier: 99108669



Respir Med. 1998 Jun;92(6):878-9.


Solitary columnar bronchial papilloma: a rare endoscopic finding.

Henry M; Landers R; Kealy WF; Bredin CP

Department of Respiratory Medicine, Cork University Hospital, Cork, Ireland.

[No abstract available.]

Unique Identifier: 99067361



Prostaglandins Leukot Essent Fatty Acids. 1998 Sep;59(3):155-61.


Effect of evening primrose and fish oils on two stage skin carcinogenesis in mice.

Ramesh G; Das UN

Division of Internal Medicine, Clinical Immunology and Biochemistry, L.V. Prasad Eye Institute, Hyderabad, India.

The effect of fish oil (FO, given in the form of MaxEPA) rich in n-3 fatty acids and evening primrose oil (EPO) rich in n-6 fatty acids on two-stage skin carcinogenesis in mice was studied. Both FO and EPO inhibited the papilloma formation to a significant degree only during the promotion stage which was associated with an increase in lipid peroxidation. Both FO and EPO inhibited the binding of benzo(a)-pyrene to skin cell DNA suggesting that this could be one of the mechanism(s) by which these oils could be preventing papilloma development. Neither EPO nor FO influenced epidermal cell proliferation. In the FO group, LA (linoleic acid), AA (arachidonic acid) and DHA (docosahexaenoic acid) were increased, whereas in the EPO group a significant increase in the AA content was noted. No specific changes in the fatty acid pattern were observed in any of the groups that could be attributed to the papilloma incidence. These results suggest that FO and EPO can influence papilloma formation which can be attributed, at least in part, to their ability to prevent benzo(a)pyrene binding to DNA and to an increase the lipid peroxidation process.

Unique Identifier: 99059119



Eur J Dermatol. 1998 Apr-May;8(3):205-6. Review.


Relevance of photo-immunosuppression for viral infections (i.e. human papilloma virus).

Vermeer BJ; Bouwes Bavinck JN

Department Dermatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.

[No abstract available.]

Unique Identifier: 98315334



RRP Foundation
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