HPV Virus Infections

HPV Virus Infections - Article in Italian

Atlante M, Mariani L, Luci M, Carico E, Diotallevi F, Iacovelli A, Vincenzoni C. IFO Polo Oncologico, Roma, Ginecologia Oncologica, Universita degli Studi di Roma, La Sapienza, Rome, Italy.

BACKGROUND: Over the past few years a series of research projects has shown that the scant or deficient immune response in HIV infection may be secondary to reduced cell resistance and/or the uncontrolled formation of free radicals. In line with these findings, subjects with HIV infection present a deficit of polyunsaturated fatty acids (the principal components of cell membranes) and many antioxidating substances, like Vitamin E and glutathione peroxidase. The high incidence of heterosexual transmission of HIV has now shown the close correlation between HIV infection and HPV infection. By analogy, we wanted to ascertain whether these deficits were also present in subjects with HPV infection and dysplastic and neoplastic lesions of the uterine cervix. Published data confirm that a HPV-positive subject has an increased risk, ranging from 40 to 200%, of contracting HIV infection. METHODS: Eighty women with HPV infection of the genital tract, at various stages. Blood levels of vitamin E and polyunsaturated fatty acids were measured using gas-chromatography; glutathione was assayed using the spectrophotometric technique. RESULTS: The alternation of the aforesaid parameters is correlated to the progress of infection and increases with the severity of lesions; Statistically significant data were recorded by comparing the group with condylomatosis with patients diagnosed with cervical carcinoma (p<0.001). CONCLUSIONS: The increased possibility that some patients are affected by an association of HPV and HIV depends on the anomalous or scarce function of many immunocompetent cells, as well the quantitative immune deficiency induced by the initial virus and the presence of various mechanisms that facilitate the development of the infection.

Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):353-9.

Human papillomavirus persistence and nutrients involved in the methylation pathway among a cohort of young women.

Sedjo RL, Inserra P, Abrahamsen M, Harris RB, Roe DJ, Baldwin S, Giuliano AR. Arizona Cancer Center, Arizona College of Public Health, University of Arizona, Tucson, Arizona 85724-5024, USA.

Persistent oncogenic human papillomavirus (HPV) infection is associated with cervical dysplasia. Cofactors, such as nutrient status, may be required for the progression of HPV infection to neoplasia. HPV DNA methylation patterns in vitro have been shown to be associated with viral transcriptional activity. Folate, vitamin B12, vitamin B6, and methionine may function to prevent cervical cancer through their role in DNA methylation. This study was conducted to examine the relationship of dietary intake of folate, vitamin B12, vitamin B6, and methionine, as well as circulating levels of folate and vitamin B12 to HPV persistence. Oncogenic HPV status was determined at baseline and at approximately 3 and 9 months postbaseline. Multivariate logistic regression analysis was used to determine the adjusted odds ratios for persistent HPV infection associated with each tertile of individual nutrient among 201 women with a persistent or intermittent HPV infection. Circulating vitamin B12 levels were inversely associated with HPV persistence (P for trend, 0.037) after adjusting for age, age at first intercourse, marital status, cigarette smoking status, race, and body mass index. In addition, women with circulating levels in the highest tertile (>493.2 pg/ml) of vitamin B12 were less likely to have a persistent infection (adjusted odds ratio = 0.4; 95% confidence interval = 0.17-0.96). No significant associations were observed between HPV persistence and dietary intake of folate, vitamin B12, vitamin B6, or methionine from food alone or from food and supplements combined or from circulating folate. These data suggest a role for circulating vitamin B12 in early cervical carcinogenesis.

JAMA. 2002 Apr 24;287(16):2120-9.

Comment in:

• JAMA. 2002 Apr 24;287(16):2140-1.

• JAMA. 2002 Sep 18;288(11):1350-1;author reply 1351-2.

• JAMA. 2002 Sep 18;288(11):1350;author reply 1351-2.

Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ; ASCCP-Sponsored Consensus Conference. Department of Pathology, College of Physicians and Surgeons of Columbia University, Room 16-404, P&S Bldg, 630 W 168th St, New York, NY 10032, USA. tcw1@columbia.edu

OBJECTIVE: To provide evidence-based consensus guidelines for the management of women with cervical cytological abnormalities and cervical cancer precursors. PARTICIPANTS: A panel of 121 experts in the diagnosis and management of cervical cancer precursors, including representatives from 29 professional organizations, federal agencies, and national and international health organizations, were invited to participate in a consensus conference sponsored by the American Society for Colposcopy and Cervical Pathology (ASCCP). EVIDENCE AND CONSENSUS PROCESS: Guidelines for the management of women with cervical cytological abnormalities were developed through a multistep process. Starting 6 months before the conference, working groups developed draft management guidelines based on formal literature reviews of English-language articles published in 1988-2001, as well as input from the professional community at large, obtained using interactive Internet-based bulletin boards. On September 6-8, 2001, the ASCCP Consensus Conference was held in Bethesda, Md. Guidelines with supporting evidence were presented and underwent discussion, revision, and voting. CONCLUSIONS: Management of women with atypical squamous cells (ASC) depends on whether the Papanicolaou test is subcategorized as of undetermined significance (ASC-US) or as cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H). Women with ASC-US should be managed using a program of 2 repeat cytology tests, immediate colposcopy, or DNA testing for high-risk types of human papillomavirus (HPV). Testing for HPV DNA is the preferred approach when liquid-based cytology is used for screening. In most instances, women with ASC-H, low-grade squamous intraepithelial lesion, HSIL, and atypical glandular cells should be referred for immediate colposcopic evaluation.

Publication Types:
• Consensus Development Conference
• Guideline
• Review

Eur J Gynaecol Oncol. 2002;23(3):203-6.

Localized distribution of human papillomavirus genotypes in the uterine cervix.

Bekkers RL, Melchers WJ, Bulten J, Boonstra H, Quint WG, Hanselaar AG, Massuger LF. Department of Gynecology and Obstetrics, University Medical Center Nijmegen, The Netherlands.

INTRODUCTION: The localization and distribution of single or multiple HPV genotypes in the uterine cervix has not been studied thus far. The present study was undertaken to determine whether single or multiple HPV genotypes detected in cervical smears originate from a single (dysplastic) area, or from different areas (dysplastic or normal) of the uterine cervix. METHODS: Of eight patients with moderate or severe dysplasia, 31 colposcopically guided biopsies of different dysplastic lesions of the uterine cervix, as well as of normal epithelium were investigated. A highly sensitive, broad spectrum, short fragment polymerase chain reaction (SPF-10 PCR) HPV detection method in combination with a line probe assay (LiPA) for simultaneous genotyping was used. RESULTS: In the uterine cervix of four of the eight patients, multiple HPV genotypes were detected. These multiple HPV genotypes were detected in different biopsies as well as within a single biopsy. In three patients, all with carcinoma in situ or microinvasive carcinoma, only a single HPV genotype, HPV 16, was found all over the cervix including in the normal epithelium. CONCLUSION: Different HPV genotypes can be detected in different dysplastic lesions as well as within single lesions, especially in patients with severe dysplasia. The severity of the lesion may possibly have a relation with the distribution of the HPV genotypes. The low number of patients and biopsies does not allow definite conclusions. However, the impact of these findings on the outcome of screening and vaccination programs remains to be elucidated.

Vopr Onkol. 2002;48(1):43-6.

Clinical and morphologic aspects of cervical papillomavirus infection

HPV Virus Infections - Article in Russian

415 female residents of the City of Tomsk and Tomsk Region (patients with cervical carcinoma--22, dysplasia stage I-III--23 and healthy subjects--71) were screened for HPV16/18 infection, which was diagnosed in 18.3%. In the cervical carcinoma group, infection was detected in 27.4%, among patients with advanced cervical dysplasia--25.7%, and in those with background pathologies and healthy females--12.3 and 38%, respectively. Infection peaks were reported for the age brackets of 31-40 years (19.7%) and 51-60 years (19.6%). HPV-infection showed a wide range of colposcopic symptoms: areas of atypical blood vessels, leukoplakia, atypical epithelium and iodine-negative patches. Papillomavirus-related morphological changes in endometrial cells were typical of those associated with any viral infection and showed no specific features.

Tumour Biol. 2002 Mar-Apr;23(2):87-92.

Telomerase assay and HPV 16/18 typing as adjunct to conventional cytological cervical cancer screening.

Ngan HY, Cheung AN, Liu SS, Liu KL, Tsao SW. Department of Obstetrics and Gynaecology, Queen Mary Hospital, University of Hong Kong, Hong Kong, China. hysngan@hkucc.hku.hk

OBJECTIVE: This study aims at exploring the potential use of telomerase activity assay and typing of human papillomaviruses (HPV) 16 and 18 in improving the identification of high-grade cervical intraepithelial neoplasia (CIN). METHODS: From 86 women with normal cervical smears and from 114 patients with abnormal cervical smears cervical scrapings were collected. The telomerase activity was assayed using the Telomerase Repeat Amplification Protocol, and HPV was detected using consensus primers and specific primers for HPV 16 and HPV 18. RESULTS: HPV 16 in cervical scrapes was significantly associated with high-grade squamous epithelial lesions on cytology and with high-grade CIN, i.e., CIN 2/3 on biopsy. The detection of HPV 18 or telomerase activity had no significant association with high-grade squamous intraepithelial lesions or high-grade CIN. CONCLUSION: The use of the telomerase activity assay in cervical scrapes, unlike HPV 16 typing, did not improve the detection of high-grade CIN. Copyright 2002 S. Karger AG, Basel

Publication Types:
• Evaluation Studies

J Hum Virol. 2001 Sep-Oct;4(5):283-7.

Human papillomavirus absence predicts normal cervical histopathologic findings with abnormal papanicolaou smears: a study of a university-based inner city population.

Khanna N, Brooks SE, Chen TT, Simsir A, Gordon NJ, Taylor G. Department of Family Medicine, University of Maryland School of Medicine and Greenebaum Cancer Center, Baltimore, Maryland 21201, USA. Nkhanna@som.umaryland.edu

INTRODUCTION: We studied the role of human papillomavirus (HPV) typing in predicting cervical dysplasia in women with abnormal Papanicolaou (Pap) test results. STUDY DESIGN/METHODS: A university colposcopy clinic-based consecutive sample of 179 women completed a questionnaire and underwent colposcopy, HPV typing (Hybrid Capture System HPV DNA Assay II; Digene Diagnostics, Gaithersburg, MD, USA), and biopsy (if indicated). RESULTS: No severe dysplasia was observed in women with low-risk HPV or in women with negative HPV test results who had a low-grade abnormality on the Pap test. High-risk (HR) HPV was present in every case of severe dysplasia on biopsy. The cumulative odds risk for cervical dysplasia was 1.11 in HIV(+) women with low-grade squamous intraepithelial lesion on the Pap test who were older than 21 years of age and HPV-HR(+). CONCLUSIONS: In the population studied, HPV typing is a valuable adjunct to a low-grade abnormality on the Pap test in predicting the absence of cervical dysplasia on biopsy. Larger prospective population-based studies are needed to study the role of HPV as a negative predictor of disease in cervical dysplasia.

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