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Biomedical subjects

Ulrike Wieland

Publications and source records attributed to Ulrike Wieland.

11 recordsLinked to original sources
PubMed2006

Imiquimod treatment of anal intraepithelial neoplasia in HIV-positive men.

OBJECTIVE: To evaluate the treatment of anal intraepithelial neoplasia (AIN) with the local immune response modifier imiquimod in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). DESIGN: Prospective, nonrandomized, open-label pilot study, with a mean follow-up time of 9(1/2) months. SETTING: Dermatology department of a university hospital. Patients Twenty-eight consecutive HIV-positive MSM with histologically confirmed perianal (n = 23) or intra-anal (n = 5) AIN. Intervention Overnight treatment with self-applied imiquimod cream (perianal AIN) or suppositories (intra-anal AIN) 3 times a week for 16 weeks. MAIN OUTCOME MEASURES: Response to treatment was documented using clinical, cytologic, and histologic criteria. Human papillomavirus (HPV) typing and HPV DNA load determination for the high-risk HPV types 16, 18, 31, and 33 were performed. RESULTS: Seventeen (61%) of all 28 patients included in the study and 17 (77%) of the 22 patients with AIN, who applied imiquimod as instructed, showed clinical and histologic clearance at the end of therapy. Four patients had residual AIN and 1 patient did not improve. Clinical response was accompanied by a sharp decline in HPV DNA loads and by a reduction in the number of HPV types, but long-term HPV clearance was rarely achieved. In the follow-up period, AIN cleared in 3 patients with residual AIN. Fourteen (78%) of 18 imiquimod responders with at least 5 five months of follow-up had a normal cytologic and clinical picture at the end of the follow-up period. Three primary responders developed a recurrence. In 6 noncompliant patients, there was no clinical or morphological improvement and the HPV DNA loads remained high. CONCLUSIONS: Imiquimod appears to be a safe and effective treatment option for AIN in HIV-positive MSM. Clinical response is accompanied by a significant decrease in high-risk HPV DNA load. These results should encourage controlled randomized studies of imiquimod treatment of AIN.

Administration, Cutaneous↗
PubMed2005

Clinical spectrum and virologic characteristics of anal intraepithelial neoplasia in HIV infection.

BACKGROUND: Anal intraepithelial neoplasia (AIN) represents a precursor lesion of invasive squamous cell carcinoma with a clear association to high-risk human papillomavirus (HPV) types. HIV infection is strongly associated with a higher prevalence of genital HPV infection, a higher incidence of AIN, and, consecutively, an increased risk for anal cancer. OBJECTIVE: The aim of this study was to determine the clinical spectrum of AIN and lesional HPV colonization in a cohort of homosexual men who were HIV positive and had a history of receptive anal intercourse. METHODS: In all, 103 men who were HIV-1 positive were screened by using clinical, proctologic, cytologic, histologic, and HPV DNA testing. RESULTS: Of all patients, 86% had anal HPV infection at their first visit. HPV-16 (53%), HPV-18 (27%), HPV-58 (22%), and HPV-83 (22%) were the most frequently found HPV types. AIN was diagnosed in 20 of the 103 patients (19.4%). High-risk HPV types were present in all AIN cases with up to 7 different high-risk and up to 5 different low-risk types per lesion. Histologically, 7 (35%), 7 (35%), and 6 (30%) of the patients had AIN grade I, II, or III, respectively. Four different types of clinical presentation could be distinguished in the 20 patients with AIN: bowenoid (1 case, 5%); erythroplakic (2 cases, 10%); verrucous (6 cases, 30%); and leukoplakic (11 cases, 55%). All verrucous lesions were graded as high-grade intraepithelial lesions in cytology, whereas 6 of the 11 leukoplakic lesions (55%) were low grade. All verrucous AIN carried at least 4 different HPV types, always including HPV-16, and the mean number of HPV types was higher in verrucous lesions than in leukoplakic lesions (5.5 vs 3.8, respectively). CONCLUSION: These data confirm the high incidence and prevalence of AIN in patients who are HPV positive with HIV infection. Four different clinical types of AIN can be distinguished that might have prognostic implications. Standardized screening programs for anal cancer prevention and treatment protocols for AIN in patients infected with HIV must be implemented.

Adult↗
PubMed2005

Human papillomavirus-DNA loads in actinic keratoses exceed those in non-melanoma skin cancers.

Recent studies suggest a role of cutaneous human papillomaviruses (HPV) in non-melanoma skin cancer (NMSC) development. In this study viral DNA loads of six frequent HPV types were determined by quantitative, type-specific real-time-PCR (Q-PCR) in actinic keratoses (AK, n=26), NMSC (n=31), perilesional tissue (n=22), and metastases of squamous cell carcinomas (SCC) (n=8) which were previously shown to be positive for HPV5, 8, 15, 20, 24, or 36. HPV-DNA loads in AK, (partially microdissected) NMSC, and perilesional skin ranged between one HPV-DNA copy per 0.02 and 14,200 cell equivalents (median: 1 HPV-DNA copy per 344 cell equivalents; n=48). In 32 of the 79 HPV-positive skin biopsies and in seven of the eight metastases viral loads were even below the detection limit of Q-PCR. Low viral loads in NMSC were confirmed by in situ-hybridization showing only a few HPV-DNA-positive nuclei per section. Viral loads in SCC, basal cell carcinomas, and perilesional tissue were similar. But, viral loads found in AK were significantly higher than in SCC (p=0.035). Our data suggest that persistence of HPV is not necessary for the maintenance of the malignant phenotype of individual NMSC cells. Although a passenger state cannot be excluded, the data are compatible with a carcinogenic role of HPV in early steps of tumor development.

Adult↗
PubMed2004

[Herpes simplex virus type 1 encephalitis].

BACKGROUND: Herpes simplex virus type 1 encephalitis (HSE) is the most frequent cause of severe sporadic viral encephalitis. In spite of the advanced modern methods for the treatment of HSE it is still associated with high mortality. Early diagnosis and prompt antiviral therapy with acyclovir are essential to improve prognosis and to prevent severe neurologic sequels. PURPOSE: This review summarizes the current knowledge on the pathogenesis, diagnosis, clinical presentation, and treatment of herpes simplex virus type 1 encephalitis. Characteristic features including magnetic resonance imaging (MRI) are illustrated by a typical case.

Acyclovir↗
PubMed2003

Expression of p16 protein identifies a distinct entity of tonsillar carcinomas associated with human papillomavirus.

Recent analyses of head and neck squamous cell carcinomas revealed frequent infections by oncogenic human papillomavirus (HPV) type 16 in tonsillar carcinomas. Concerning involvement of risk factors, clinical course of the disease, and prognosis there are strong indications arguing that the HPV-positive tonsillar carcinomas may represent a separate tumor entity. Looking for a surrogate marker, which in further epidemiological studies could replace the laborious and expensive HPV detection and typing we analyzed p16 protein expression in 34 tonsillar carcinoma for correlation to HPV status and load of viral DNA. p16 has been shown to be of diagnostic value for clinical evaluation of cervical dysplasia. We found 53% of the tested tonsillar carcinomas to be HPV-positive. Fifty-six percent of all tumors tested were immunohistochemically positive for the p16 protein. In 16 of 18 of the HPV-positive carcinomas diffuse p16 expression was observed. In contrast, only one of the HPV-negative carcinomas showed focal p16 staining (P < 0.001). As determined by laser-assisted microdissection and quantitative real-time polymerase chain reaction, p16 expression correlated with the presence of HPV-DNA in the individual tumor specimens. Clinical outcome analysis revealed significant correlation of p16 expression with increased disease-free survival (P = 0.02). These data indicate that p16 is a technically simple immunohistological marker, applicable for routine pathological histology, and its prognostic value for survival is fully equivalent to HPV-DNA detection.

Adolescent↗
PubMed2003

Human papillomavirus-negative ileostomal chronic papillomatous dermatitis.

BACKGROUND: Papillomatous stoma-related skin lesions may result from irritant reactions or infection with epidermodysplasia verruciformis human papillomavirus (HPV) types. METHODS: We report upon a papillomatous lesion at the ileostoma of a 63-year-old male with familial adenomatous polyposis and colorectal adenocarcinoma. We thoroughly tested the lesion for HPV using immunohistochemistry, transmission electron microscopy, and polymerase chain reaction analyses. RESULTS: The lesion was a fleshy, multilobulated, and verrucous plaque, with hyperkeratosis, hypergranulosis, acanthosis and marked papillomatosis. The clinical and light microscopic features were suggestive of a condyloma. However, no HPV was detected. CONCLUSIONS: We suggest that the lesion most likely represents chronic papillomatous dermatitis, a reaction to mechanical and/or chemical irritation usually associated with urostomies and only rarely observed with ileostomies. This case highlights the clinical, diagnostic and therapeutic aspects of an unusual cutaneous morbidity associated with ileostomies.

Chronic Disease↗
PubMed2002

Human papillomavirus-positive tonsillar carcinomas: a different tumor entity?

Human papillomavirus (HPV) infections are thought to be one of the causal factors in the development of head and neck squamous cell carcinomas (HNSCC), particularly in tumors arising from the Waldeyer's tonsillar ring. We screened 98 carefully stratified HNSCC and different control tissues for the presence of HPV DNA by nested polymerase chain reaction (PCR) specific for genital- and Epidermodysplasia verruciformis (EV)-associated HPVs and by HPV16-specific single step PCR. Typing was performed by direct sequencing and/or sequencing of cloned amplimers. On average HNSCC showed rather low HPV DNA prevalences; 18% of the oral cavity cancers, 8% of nasopharyngeal cancers, 25% of hypopharyngeal cancers and 7% of laryngeal cancers were HPV DNA positive. In contrast, HPV sequences could be detected in 45% of the oropharyngeal cancers, particularly tonsillar carcinomas (58%). Tonsillar carcinomas were significantly more likely to be HPV positive than tumors from any other site ( P<0.001). All tonsillar cancers contained oncogenic HPV types, predominantly HPV16 (13 of 14; 93%). Unaffected tonsils were available from two of these patients, but both tested negative for HPV DNA. Furthermore, no HPV DNA could be found in tonsillar biopsy specimens from control groups. Localization and load of HPV DNA was determined in HPV16-positive tonsillar carcinomas, their metastases and in unaffected mucosa using laser-assisted microdissection and subsequent real time fluorescence PCR. We demonstrated that the HPV genome is located in the cancer cells, whereas the infection of normal mucosa is a rare event. Quantification of HPV16 DNA in samples of seven patients yielded viral loads from 6 to 153 HPV DNA copies per beta-globin gene copy and the load values in both locations were roughly comparable. These loads are comparable with data shown for other HPV-associated lesions. Statistical evaluation of data related to clinicopathological parameters showed a significant correlation of the HPV positivity of tonsillar carcinomas with tumor grading ( P=0.008) and alcohol consumption ( P=0.029). Taken together our findings show a preferential association of HPV DNA with tonsillar carcinomas. Furthermore our results argue for HPV-positive tonsillar carcinomas representing a separate tumor entity, which is less dependent on conventional HNSCC risk factors.

Carcinoma, Squamous Cell↗