Human Papilloma Virus - Cancer

Moberg M, Gustavsson I, Wilander E, Gyllensten U. Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala 751 85, Sweden.

High loads of human papillomavirus (HPV) 16 and HPV 18/45 increase the risk of developing invasive cervical carcinoma, revealing higher risk in percentiles of highest viral loads for HPV 16 (odds ratio (OR) 58.7, 95% confidence interval (CI) 21.9-151.4) compared to HPV 18/45 (OR 3.3, 95% CI 1.5-7.2). Thus, HPV load is a type-dependent risk marker for invasive carcinoma.

Gynecol Oncol. 2005 May;97(2):342-7.

The expression of MAGE and GAGE genes in uterine cervical carcinoma of Korea by RT-PCR with common primers.

Chang HK, Park J, Kim W, Kim K, Lee M, Park U, Choi B. Department of Pathology, Kosin University Medical College, 34 AmNam-Dong, Suh-Ku, Pusan, 602-702, South Korea.

BACKGROUND: Melanoma antigen genes (MAGE) and GAGE genes are encoded by genes that are silent in virtually all normal adult tissues but are expressed in tumors from various tissues. These gene products are targets for specific immunotherapy as they are presented by HLA I molecules and recognized by autologous cytotoxic T-lymphocytes. However, the characteristics of these genes, especially in uterine cervical cancer are relatively unknown. PURPOSE: This study evaluated the prevalence of MAGE and GAGE by reverse transcription-polymerase chain reaction (RT-PCR) with common primers and discusses clinical implications in cervical carcinoma. MATERIALS AND METHODS: Fresh tissue from 37 cases of primary squamous cell carcinoma and normal cervical mucosa were evaluated for clinicopathologic parameters including Human Papilloma Virus (HPV)-16,18 infection by PCR, tumor stage by FIGO classification and lymph node involvement. RT-nested PCR for the MAGE and GAGE genes was performed with common primers and DNA sequencing after subcloning was used for identification of PCR products of MAGE. Formalin-fixed paraffin embedded material from the same specimen was analyzed by in situ RT-PCR for MAGE. RESULTS: Expression of MAGE and GAGE was not observed in normal tissues. Eleven out of 37 cases expressed MAGE mRNA (29.7%): analysis of subtypes identified one case of MAGE-1, two cases of MAGE-4b, six cases of MAGE-3, and two unknown subtypes. Thirteen out of 37 cases (35.1%) expressed GAGE mRNA. No significant relationships between expression of these genes and FIGO staging, lymph node metastasis or HPV infection were found. CONCLUSION: Expression of MAGE and GAGE may be involved in the development of uterine cervical carcinoma from intraepithelial neoplasia, although without distinct prognostic significance. MAGE and GAGE genes have the potential to be used as targets for the treatment of uterine cervical carcinoma.

J Natl Cancer Inst. 2005 Apr 20;97(8):577-86.

Genes Chromosomes Cancer. 2005 Jul;43(3):260-72.

A region on human chromosome 4 (q35.1-->qter) induces senescence in cell hybrids and is involved in cervical carcinogenesis.

Backsch C, Rudolph B, Kuhne-Heid R, Kalscheuer V, Bartsch O, Jansen L, Beer K, Meyer B, Schneider A, Durst M. Gynakologische Molekularbiologie, Abteilung Frauenheilkunde, Frauenklinik der Friedrich-Schiller-Universitat Jena, Germany.

Human papillomavirus (HPV) types 16 and 18 are known to play a major role in cervical carcinogenesis. Additional genetic alterations are required for the development and progression of cervical cancer. Previously, we showed that the introduction of an entire human chromosome 4 into HPV-immortalized cells by microcell-mediated chromosome transfer (MMCT) can induce senescence in cell hybrids. In the present study, we established eight new murine donor cell lines harboring different fragments of the human chromosome 4. These were tested for their ability to induce senescence by MMCT into HPV16-immortalized keratinocytes (HPK II) and cervical carcinoma cells (HeLa). By exclusion, we could identify a region for a putative senescence gene or genes at 4q35.1-->qter. Further evidence that this locus may be involved in cervical carcinogenesis was obtained by studying sections of high-grade cervical intraepithelial neoplasias (CIN2/3) and cervical cancers from 87 women using a combination of interphase fluorescence in situ hybridization (I-FISH) and microsatellite PCR. I-FISH indicated copy number loss at 4q34-->qter. Microsatellite analysis showed that loss of one or more alleles at chromosome 4 was more frequent in the cervical carcinomas than in the CINs. Loss of heterozygosity (LOH) affected four areas, D4S412 (4p16.3), D4S2394 (4q28.2), D4S3041 (4q32.3), and D4S408 (4q35.1), and was highest at D4S408. LOH at terminal 4q has been reported previously for cervical carcinomas and other human malignancies. This is the first report associating allelic loss at 4q34-->qter with high-grade intraepithelial neoplasia and cervical carcinoma, and the first experimental evidence that this locus or these loci can induce senescence in cervical carcinoma cells and HPV16-immortalized cells. (c) 2005 Wiley-Liss, Inc.

Zhonghua Liu Xing Bing Xue Za Zhi. 2004 Nov;25(11):921-4.

Association between high-risk human papillomavirus DNA load and cervical intraepithelial lesion.

Human Papilloma Virus - Article in Chinese

OBJECTIVE: To determine the association between viral load of high risk type human papillomavirus (HR-HPV) and stage of cervical intraepithelial neoplasia (CIN) lesion. METHODS: Cervical exfoliated cells were collected from 1997 women aged 35-45 in a cross-sectional screening study. HPV DNA was detected by hybrid capture 2 (HC2) system, and viral load was measured by the ratios of relative light units compared to standard positive control (RLU/PC). Log10RLU/PC were categorized into four groups: negative (< 0), low viral load (0 - 1.12), medium viral load (1.13 - 2.23), and high viral load (2.24 - 3.37). Cervical lesions were diagnosed by biopsies as normal, CIN 1, CIN 2-3, and squamous cervical cancer (SCC). Association between HR-HPV and CINs were evaluated by unconditional multinomial logistic regression. RESULTS: 100% (12/12) SCC, 97.3% (72/74) of CIN 2-3, 58.3% (74/127) of CIN 1, and 11.5% (205/1784) of normal women were positive for HPV DNA. The median log10RLUs for the positive women with SCC, CIN 2-3, CIN 1 and in normal women were 2.60, 2.32, 2.18 and 1.18 respectively. The odds ratio (OR) between low viral load of HPV DNA and CIN 1 was 3.8 (1.9 - 7.3) while between high viral load and CIN 2-3 was OR=865.9 (200.1 - 3738.0) which showed that higher viral load could increase the risk of cervical lesions (P <0.001). CONCLUSION: Both cervical cancer and CINs were highly influenced by HR-HPV viral load.

J Infect Dis. 2005 Apr 1;191(7):1129-39. Epub 2005 Feb 21.

Effects of bacterial vaginosis and other genital infections on the natural history of human papillomavirus infection in HIV-1-infected and high-risk HIV-1-uninfected women.

Watts DH, Fazarri M, Minkoff H, Hillier SL, Sha B, Glesby M, Levine AM, Burk R, Palefsky JM, Moxley M, Ahdieh-Grant L, Strickler HD. National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892-7510, USA.

BACKGROUND: Whether the natural history of human papillomavirus (HPV) infection is affected by bacterial vaginosis (BV) or Trichomonas vaginalis (TV) infection has not been adequately investigated in prospective studies. METHODS: Human immunodeficiency virus 1 (HIV-1)-infected (n=1763) and high-risk HIV-1-uninfected (n=493) women were assessed semiannually for BV (by Nugent's criteria), TV infection (by wet mount), type-specific HPV (by polymerase chain reaction with MY09/MY11/HMB01 HPV primers), and squamous intraepithelial lesions (SIL) (by cytological examination). Sexual history was obtained from patient report at each visit. Risk factors for prevalent and incident HPV infection and SIL were evaluated by use of multivariate models. RESULTS: BV was associated with both prevalent and incident HPV infection but not with duration of HPV infection or incidence of SIL. TV infection was associated with incident HPV infection and with decreased duration and lower prevalence of HPV infection. TV infection had no association with development of SIL. Effects of BV and TV infection were similar in HIV-1-infected and high-risk HIV-1-uninfected women. HIV-1 infection and low CD4(+) lymphocyte count were strongly associated with HPV infection and development of SIL. CONCLUSIONS: BV and TV infection may increase the risk of acquisition (or reactivation) of HPV infection, as is consistent with hypotheses that the local cervicovaginal milieu plays a role in susceptibility to HPV infection. The finding that BV did not affect persistence of HPV infection and that TV infection may shorten the duration of HPV infection helps explain the lack of effect that BV and TV infection have on development of SIL.

Human Papilloma Virus - HPV and Cancer Links

Cervical Cancer Overview - From the Daily Apple - very nice overview section on cervical cancer.

General Information about Gyn Cancers - Includes links to basic info about symptoms, doctors, statistics, where to get support, and lots more.