HPV Virus Infections - Detection

Simsir A, Brooks S, Cochran L, Bourquin P, Ioffe OB. Departments of Pathology and Gynecologic Oncology, University of Maryland Medical System, Baltimore, Maryland, USA. simsia01@med.nyu.edu

OBJECTIVE: To assess the prevalence and spectrum of Pap smear (PS) abnormalities in sexually active adolescents in comparison to adult women in order to determine whether management of adolescents should differ from that of adults. STUDY DESIGN: Five hundred twenty-four adolescents who had an initial PS at our institution from January to September 1997 were followed for 36 months with repeat PS and/or cervical biopsy. Initial PS results were compared with those of adult women. The chi 2 test was used to calculate the statistical significance of differences between the two groups. The qualified atypical squamous cells of undetermined significance (ASCUS) cytologic diagnosis in adolescents was correlated with follow-up data. RESULTS: The overall prevalence of squamous intraepithelial lesions (SILs) in adolescents was 29% as compared to 23% in adults. Almost all initial squamous lesions were ASCUS and low grade squamous intraepithelial lesion (LSIL); only one case of high grade squamous intraepithelial lesion (HSIL) was detected. On follow-up 18% and 2.4% of adolescents developed LSIL and HSIL, with a LSIL/HSIL ratio of 8/1 as compared to 5/1 in adults. The average time from initial PS to detection of HSIL was 20 months. All patients with HSIL except one had had one or more previous abnormal PSs. The positive predictive values (PPVs) for subsequent dysplasia for ASCUS favor reactive (ASCUS.R), ASCUS not otherwise specified (ASCUS.NOS) and ASCUS favor dysplasia (ASCUS.D) in adolescents were .13, .17 and .31, respectively. ASCUS.NOS (P = .01) and ASCUS.D (P = .007) were strong indicators of dysplasia as compared to ASCUS.R. CONCLUSION: PS abnormalities are more common in sexually active adolescents, with a significantly higher prevalence of LSIL over HSIL as compared to adult women. Given the natural history of HPV infection, we recommend follow-up with cytology rather than colposcopy/biopsy for adolescents with ASCUS and LSIL PSs. Qualification of ASCUS is useful in determining which adolescents are at the highest risk of cervical dysplasia.

J Infect Dis. 2002 Aug 15;186(4):462-9. Epub 2002 Aug 2.

Incidence, prevalence, and clearance of type-specific human papillomavirus infections: The Young Women's Health Study.

Giuliano AR, Harris R, Sedjo RL, Baldwin S, Roe D, Papenfuss MR, Abrahamsen M, Inserra P, Olvera S, Hatch K. Arizona Cancer Center, Tucson 85724-5024, USA. agiuliano@azcc.arizona.edu

The natural history of type-specific human papillomavirus (HPV) infections was examined in a cohort of 331 women aged 18-35 years who self-referred for routine gynecological care. Participants underwent a gynecological examination at baseline and at approximately 4 and approximately 10 months after baseline. Cervical samples were collected for HPV testing and genotyping at each visit, as was information on reproductive, sexual, and medical histories. The rate of new HPV infections was 2.9% per month; the highest rates were observed for HPV types 16, 39, 84, and 51. Among women who tested negative for HPV at baseline, the cumulative probability of acquiring an oncogenic HPV strain during a 12-month follow-up period was 0.32, compared with 0.18 for nononcogenic strains. Women who had had >/=1 new male sex partner in the recent past were significantly more likely to acquire a new HPV infection (relative hazard, 2.39; 95% confidence interval, 1.20-4.76). The median time to clearance of infection was significantly longer for oncogenic strains (9.8 months) than for nononcogenic strains (4.3 months).

Anticancer Res. 2002 May-Jun;22(3):1655-60.

Frequent detection of human papilloma viruses in cervical dysplasia by PCR single-strand DNA-conformational polymorphism analysis.

Nakagawa H, Sugano K, Fujii T, Kubushiro K, Tsukazaki K, Nozawa S. Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan. hnakagaw@mc.med.keio.ac.jp

BACKGROUND: To clarify the pathogenicity of multiple human papilloma virus (HPV) infection, we applied SSCP (single-strand DNA conformation polymorphism) analysis for cervical neoplastic lesions. MATERIALS AND METHODS: Two hundred and sixty-six cervical swab specimens from normal cervix (n=64), cervical dysplasia (n=95), carcinoma in situ (n=79) and cervical cancer (n=28), were studied by nested PCR-SSCP analysis using L1 consensus primers. RESULTS: In 95 samples of cervical dysplasia, HPV infection was detected in 98.9% (94 out of 95), multiple HPV infection was detected in 38.3% (36 out of 94). In 19 squamous cell carcinomas (SCC) and 9 adenocarcinomas, the detection rate of HPV infection was 84.2% (16 out of 19) and 55.6% (5 out of 9), respectively, and all HPV-positive cases showed infection of a single HPV, among which HPV 16 occupied 68.6% (11 out of 16) in SCC and HPV 18 occupied 100% (5 out of 5) in adenocarcinoma. CONCLUSION: Multiple HPV infections may be concerned with pathogenicity in cervical dysplasia; however, the single infection with only a few HPV types, such as type 16 in SCC and type 18 in adenocarcinoma, may play a role in cervical carcinogenesis.

Anal Quant Cytol Histol. 2002 Jun;24(3):137-46.

Fully automated proteomic detection of cervical dysplasia.

Keesee SK, Domanik R, Patterson B. Molecular Diagnostics, Inc., Chicago, Illinois 60610, USA.

OBJECTIVE: To evaluate the efficacy of two biomarkers, transferrin receptor (TfR) and epidermal growth factor receptor (EGFR), for the early detection of cervical dysplasia and to explore the relationship of E5, one of three viral oncogenes expressed by the human papillomavirus (HPV), to TfR and EGFR. STUDY DESIGN: Two hundred seventy-four patients were evaluated in two separate preclinical studies using EGFR and TfR in fluorescent antibody-based assays. Cervical epithelial monolayers on glass slides were immunostained and scanned using an automated microscope platform and proprietary analysis software. Sensitivity and specificity were calculated in patient cohorts for both assays. RESULTS: Sensitivity for high grade dysplasia (HSIL) and invasive cancer in the EGFR study was 100%; specificity was 73.3%. The TfR assay, which is completely automated, demonstrated sensitivity for HSIL and invasive cancer of 96.3%, with a specificity of 81.3% in 211 patients, from five different clinical sites. CONCLUSION: Both EGFR and TfR assays detected HSIL with very high accuracy (100% and 96.3%, respectively). Specificity of the TfR assay was slightly higher (81.3%) than that of the EGFR assay (73.3%). HPV E5-induced disruption of intracellular endosomal acidification and its effects upon both EGFR and TfR may provide the specific mechanistic connection between overexpression of these receptor proteins, and HPV in fection and integration. EGFR and especially TfR show great promise as biomarkers in a highly sensitive and specific, fully automated assay for the early detection of cervical dysplasia.

Publication Types:
• Evaluation Studies

Perrons C, Kleter B, Jelley R, Jalal H, Quint W, Tedder R. Department of Virology, Royal Free and University College Medical School, London, United Kingdom. c.perrons@ucl.ac.uk

Human papillomavirus (HPV) is the main etiological agent of cervical cancer. There is a large number of HPV genotypes and therefore a need to distinguish the high risk HPV genotypes associated with invasive cancer from the low risk. Because persistence of high risk HPV infection is necessary for progression of a pre-invasive cervical change one needs to identify the individual genotype to see if it persists. PCR amplification of HPV DNA is described using two consensus primer systems from cervical cells. Amplified HPV DNA was genotyped using a reverse hybridization line probe assay (LiPA). HPV DNA was amplified from 42% of samples by MY09/11 and from 80% by SPF10. In 42 samples HPV DNA was detected by both primer sets and in 38 samples only the SPF10 primers detected HPV DNA. The LiPA detected 21 different HPV genotypes (13 high risk) in this cohort of samples. Forty-three percent contained a single HPV genotype and 24% contained multiple infections (2-5 genotypes). Overall, high risk HPV genotypes were detected in 48% of the cervical samples, the most frequent types were 16, 18, 31, and 51. The proportion of high risk HPV genotypes increased with more severe cytological abnormalities. This study demonstrates that the SPF10 primer set is more sensitive than the MY09/11 primer set and that genotyping by LiPA tells us if the HPV infection is caused by a high risk type and if the infection is mixed. Additionally LiPA provides information about the individual genotype when looking for persistence of infection. HPV DNA detection and genotyping is therefore a useful tool in the colposcopy clinic, used in conjunction with cytology. Copyright 2002 Wiley-Liss, Inc.

HPV Virus Infections - Detection of HPV Links

Department of Pathology - Read about the methods of detection of HPV infection.

Screening for HPV - An extended article on many methods for detection of Human Papillomavirus (HPV) infection in different tissues. The thin layer-based technology in cervical cancer screening is described, which allows both