HPV Virus Medical - Risks

Zelmanowicz AD, Schiffman M, Herrero R, Goldstein AM, Sherman ME, Burk RD, Gravitt P, Viscidi R, Schwartz P, Barnes W, Mortel R, Silverberg SG, Buckland J, Hildesheim A. Programa de Pos-graduacao em Epidemiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Previous work suggests that cervical cancer may aggregate in families. We evaluated the association between a family history of gynecological tumors and risk of squamous cell and adenocarcinomas of the cervix in 2 studies conducted in Costa Rica and the United States. The Costa Rican study consisted of 2,073 women (85 diagnosed with CIN3 or cancer, 55 diagnosed with CIN2 and 1,933 controls) selected from a population-based study of 10,049 women. The U.S. study consisted of 570 women (124 with in situ or invasive adenocarcinomas, 139 with in situ or invasive squamous cell carcinomas of the cervix and 307 community-based controls) recruited as part of a multicentric case-control study in the eastern part of the United States. Information on family history of cervical and other cancers among first-degree relatives was ascertained via questionnaire. Information on other risk factors for cervical cancer was obtained via questionnaire. Human papillomavirus (HPV) exposure was assessed in both studies using broad spectrum HPV L1-based PCR testing of exfoliated cervicovaginal cells and in Costa Rica by additional testing of plasma collected from participants for antibodies against the L1 protein of HPV types 16, 18, 31 and 45 by ELISA. A family history of cervical cancer in a first-degree relative was associated with increased risk of squamous tumors in both studies (odds ration [OR] = 3.2 for CIN3/cancer vs. controls; 95% confidence interval [CI] = 1.1-9.4 in Costa Rica; OR = 2.6 for in situ/invasive squamous cell carcinoma cases vs. controls, 95% CI = 1.1-6.4 in the Eastern United States study). These associations were evident regardless of whether the affected relative was a mother, sister or daughter of the study participant. Furthermore, observed effects were not strongly modified by age. In Costa Rica, the effect persisted in analysis restricted to HPV-exposed individuals (OR = 3.0; 95% CI = 1.0-9.0), whereas in the Eastern United States study there was evidence of attenuation of risk in analysis of squamous carcinoma cases restricted to HPV positive women (OR = 1.4; 95% CI = 0.29-6.6). No significant association was observed between a family history of cervical cancer in a first-degree relative and adenocarcinomas (OR = 1.3; 95% CI = 0.43-3.9). History of gynecological tumors other than cervical cancer in a first-degree relative was not significantly associated with risk of disease in either study. These results are consistent with a role of host factors in the pathogenesis of squamous cell cervical cancer, although familial aggregation due to shared environmental exposures cannot be ruled out. (c) 2005 Wiley-Liss, Inc.

Cancer Epidemiol Biomarkers Prev. 2005 May;14(5):1165-70.

Smoking Is a Risk Factor for Cervical Intraepithelial Neoplasia Grade 3 among Oncogenic Human Papillomavirus DNA-Positive Women with Equivocal or Mildly Abnormal Cytology.

McIntyre-Seltman K, Castle PE, Guido R, Schiffman M, Wheeler CM. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Room 7074, 6120 Executive Boulevard, EPS MSC 7234, Bethesda, MD 20892-7234. castlep@mail.nih.gov.

BACKGROUND: Smoking is a potential risk factor for cervical cancer and its immediate precursor, cervical intraepithelial neoplasia grade 3 (CIN3), but few studies have adequately taken into account the possible confounding effect of oncogenic human papillomavirus (HPV) infection.METHODS: Women (n = 5,060) with minimally abnormal Papanicolaou smears were enrolled in the ASCUS and LSIL Triage Study, a clinical trial to evaluate management strategies, and were seen every 6 months for the 2-year duration of the study. Cervical specimens were tested for HPV DNA using both Hybrid Capture 2 and PGMY09/11 L1 consensus primer PCR with reverse line blot hybridization for genotyping. Multivariate logistics regression models were used to assess associations [odds ratio (OR) with 95% confidence intervals (95% CI)] between smoking behaviors and rigorously reviewed cases of cervical intraepithelial neoplasia grade 3 or cancer (>/=CIN3) identified throughout the study (n = 506) in women with oncogenic HPV (n = 3,133).RESULTS: Current smoking was only weakly associated with increased HPV infection. Among infected women, current smokers (OR, 1.7; 95% CI, 1.4-2.1) and past smokers (OR, 1.7; 95% CI, 1.2-2.4) were more likely to be diagnosed with >/=CIN3 than nonsmokers. Greater smoking intensity (P(Trend) < 0.0005) and duration (P(Trend) < 0.0005) increased the strength of the association, with smoking >/=2 packs/d (OR, 3.3; 95% CI, 1.5-7.5) and smoking for >/=11 years (OR, 2.1; 95% CI, 1.5-2.9) most strongly associated with >/=CIN3 as compared to non-smokers. The effects of intensity and duration seemed additive.CONCLUSIONS: Women with oncogenic HPV and minimally abnormal Papanicolaou smears who smoke were up to three times more likely to be diagnosed with >/=CIN3 than nonsmokers. Smoking cessation trials targeting this population might be warranted.

Gynecol Oncol. 2005 May 12; [Epub ahead of print]

Human papillomavirus type and tobacco use as predictors of survival in early stage cervical carcinoma.

Wright JD, Li J, Gerhard DS, Zhang Z, Huettner PC, Powell MA, Gibb RK, Herzog TJ, Mutch DG, Trinkaus KM, Rader JS. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, 4911 Barnes Hospital Plaza, Box 8064, St. Louis, MO 63110, USA.

OBJECTIVE.: Molecular and environmental co-factors are known risk factors for cervical cancer. The aim of this study was to define the prognostic significance of HPV 18 and its phylogenetically related viruses and smoking on survival in patients with early stage cervical cancer. METHODS.: HPV typing was performed on stage IB-IIB cervical tumors. Subjects positive for HPV 18 or 45 were compared to the remainder of the cohort and to women with tumors containing HPV 16, 31, or 52. Tobacco use was ascertained by patient questionnaire. RESULTS.: Tumors of 255 women were evaluated. The presence of HPV 18 or 45 was associated with decreased survival. In a multivariable Cox proportional hazards analysis comparing patients with HPV 18 or 45 containing tumors to the rest of the cohort, the hazard ratio for death from cervical cancer was 2.08 (95% CI, 1.07-4.04). The hazard ratio for death from cervical cancer was 2.41 (95% CI, 1.17-4.96) when the HPV 18 and 45 group was compared to women with HPV 16 or its related viruses, 31 and 52. Smoking was associated with a decreased survival for women with HPV 18 or 45, even after adjusting for other known prognostic factors (P = 0.031). CONCLUSIONS.: In addition to pathologic indicators, molecular and environmental co-factors are important determinates of outcome in early stage cervical cancer. The presence of HPV 18 or 45 is associated with a decreased survival. The adverse effect of HPV 18 and 45 on survival is compounded by tobacco use.

Mem Inst Oswaldo Cruz. 2005 Feb;100(1):1-12. Epub 2005 Apr 12.

Immune response in cervical dysplasia induced by human papillomavirus: the influence of human immunodeficiency virus-1 co-infection -- review.

Nicol AF, Fernandes AT, Bonecini-Almeida Mda G. Departamento de Microbiologia, Imunologia e Parasitologia, Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz, Av. Brasil 4365, 21040-900 Rio de Janeiro, RJ, Brazil.

Human immunodeficiency virus (HIV-1) has become an important risk factor for human papillomavirus (HPV) infection and the development of HPV associated lesions in the female genital tract. HIV-1 may also increase the oncogenicity of high risk HPV types and the activation of low risk types. The Center for Disease Control and Prevention declared invasive cervical cancer an acquired immunodeficiency virus (AIDS) defining illness in HIV positive women. Furthermore, cervical cancer happens to be the second most common female cancer worldwide. The host's local immune response plays a critical factor in controlling these conditions, as well as in changes in the number of professional antigen-presenting cells, cytokine, and MHC molecules expression. Also, the production of cytokines may determine which arm of the immune response will be stimulated and may influence the magnitude of immune protection. Although there are many studies describing the inflammatory response in HPV infection, few data are available to demonstrate the influence of the HIV infection and several questions regarding the cervical immune response are still unknown. In this review we present a brief account of the current understanding of HIV/HPV co-infection, emphasizing cervical immune response.

J Rural Health. 2005 Spring;21(2):149-57.

Geographic disparities in cervical cancer mortality: what are the roles of risk factor prevalence, screening, and use of recommended treatment?

Yabroff KR, Lawrence WF, King JC, Mangan P, Washington KS, Yi B, Kerner JF, Mandelblatt JS. Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD 20892-7344, USA. yabroffr@mail.nih.gov

CONTEXT: Despite advances in early detection and prevention of cervical cancer, women living in rural areas, and particularly in Appalachia, the rural South, the Texas/Mexico border, and the central valley of California, have had consistently higher rates of cervical cancer mortality than their counterparts in other areas during the past several decades. METHODS: This paper reviews the published literature from 1966 to July 2002 to assess three potential pathways underlying this excess mortality--high human papilloma virus (HPV) prevalence, lack of or infrequent screening and advanced disease at diagnosis, and under-use of recommended treatment and shorter survival. FINDINGS: Living in rural areas may impose barriers to cervical cancer control, including lack of transportation and medical care infrastructures. Population characteristics that place women at greater risk for developing and dying from cervical cancer, such as low income, lack of health insurance, and physician availability, are concentrated in rural areas. Published data, however, are insufficient to identify the key reasons for the observed mortality patterns. CONCLUSIONS: At this time, given the lack of definitive evidence in the published literature, decisions about priorities in areas with high rates of cervical cancer mortality will depend on knowledge of current levels of screening, incidence, and stage distribution; and service delivery infrastructures, resources, and acceptability of interventions to the target population.

Ethn Health. 2005 Feb;10(1):3-18.

Influence of beliefs about cervical cancer etiology on Pap smear use among Latina immigrants.

McMullin JM, De Alba I, Chavez LR, Hubbell FA. Department of Medicine, University of California, Irvine, 101 City Drive, Bldg 200 #720, Orange, CA 92868-4076, USA.

OBJECTIVE: To assess Latina immigrants' beliefs about the role of sexual activities in cervical cancer etiology and the impact of the beliefs on Papanicolaou (Pap) smear use. Previous research has found that Latinas, particularly immigrants, believe that cervical cancer is related to 'unwise' sexual activities; however, their beliefs about the nature of the relationship are unclear. DESIGN: We conducted semi-structured face-to-face interviews with a non-probability purposive sample of 20 Mexican immigrant women who resided in Orange County, California regarding their beliefs about risk factors for cervical cancer and Pap smear use. We used qualitative content analysis to identify major themes. Three investigators independently reviewed transcripts of the audio-taped interviews to identify themes and came to a consensus about them. RESULTS: The women had a mean age of 39 years and had resided in the USA for an average of 16.3 years. We identified several themes. The majority of respondents had limited knowledge about cervical cancer and no knowledge about human papillomavirus (HPV); believed that infections caused by physical trauma, certain sexual activities, and poor hygiene caused cervical cancer; believed that they only needed a Pap smear if they developed symptoms of a pelvic infection; and felt that women who engaged in 'unwise' sexual behaviors, in particular, should receive regular Pap smear exams. CONCLUSION: The results suggest that culturally related beliefs about the etiology of cervical cancer play a role in the decision to obtain Pap smears for Latina immigrants. The findings may help to explain why researchers have found Latino ethnicity to be an independent predictor of Pap smear use. They also suggest that programs designed to improve cervical cancer screening, particularly among Latina immigrants, should stress the nature of HPV transmission, its role in the etiology of cervical cancer, and the importance of Pap smear screening in the absence of symptoms.

Int J Gynaecol Obstet. 2005 May;89 Suppl 2:S55-9.

Preventing cervical cancer in low-resource settings: How far have we come and what does the future hold?

Tsu VD, Pollack AE. Program for Appropriate Technology in Health (PATH), 1455 NW Leary Way, Seattle, WA 98107-5136, USA.

The Alliance for Cervical Cancer Prevention (ACCP) came together in 1999 to answer key research questions and to advocate for greater global and national interest in reducing the heavy burden of morbidity and mortality caused by this preventable disease. Visual inspection with acetic acid (VIA), visual inspection with Lugol's iodine (VILI), and human papillomavirus (HPV) tests have been shown to be viable alternatives to traditional cytology. ACCP experience confirmed that cryotherapy is a safe and effective method that is acceptable to women and can be delivered by a range of health providers, including nonphysicians. Programs can maximize coverage by accommodating local needs and involving community leaders and women in planning and implementation. Advocacy efforts have led to significant policy changes and galvanized support for cervical cancer prevention. Despite the prospect of new HPV vaccines, screening will be needed for at least the next 30-40 years. Our experience has shown that with creativity, flexibility, and well-focused use of resources, the inequitable burden of cervical cancer borne by women in poor countries can be sharply reduced.

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