RRP Medical Reference Service
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
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:
P.O. Box 6643
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Marshfield WI 54449
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...
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 activities.
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 cancer]
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.
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 carcinogenesis.
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 childhood.
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 cases)]
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 infection]
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.
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]
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 mechanisms.
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 papilloma.
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 WORDS)
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.
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 TRUNCATED AT 250 WORDS)
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 negligible.
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