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Catarino R, Petignat P, Dongui G, Vassilakos P. Cervical cancer screening in developing countries at a crossroad: Emerging technologies and policy choices. World J Clin Oncol 2015; 6:281-290. [PMID: 26677441 PMCID: PMC4675913 DOI: 10.5306/wjco.v6.i6.281] [Citation(s) in RCA: 158] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 09/03/2015] [Accepted: 10/27/2015] [Indexed: 02/06/2023] Open
Abstract
Cervical cancer (CC) represents the fourth most common malignancy affecting women all over the world and is the second most common in developing areas. In these areas, the burden from disease remains important because of the difficulty in implementing cytology-based screening programmes. The main obstacles inherent to these countries are poverty and a lack of healthcare infrastructures and trained practitioners. With the availability of new technologies, researchers have attempted to find new strategies that are adapted to low- and middle-income countries (LMIC) to promote early diagnosis of cervical pathology. Current evidence suggests that human papillomavirus (HPV) testing is more effective than cytology for CC screening. Therefore, highly sensitive tests have now been developed for primary screening. Rapid molecular methods for detecting HPV DNA have only recently been commercially available. This constitutes a milestone in CC screening in low-resource settings because it may help overcome the great majority of obstacles inherent to previous screening programmes. Despite several advantages, HPV-based screening has a low positive predictive value for CC, so that HPV-positive women need to be triaged with further testing to determine optimal management. Visual inspection tests, cytology and novel biomarkers are some options. In this review, we provide an overview of current and emerging screening approaches for CC. In particular, we discuss the challenge of implementing an efficient cervical screening adapted to LMIC and the opportunity to introduce primary HPV-based screening with the availability of point-of-care (POC) HPV testing. The most adapted screening strategy to LMIC is still a work in progress, but we have reasons to believe that POC HPV testing makes part of the future strategies in association with a triage test that still needs to be defined.
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Rosales-Mendoza S, Govea-Alonso DO. The potential of plants for the production and delivery of human papillomavirus vaccines. Expert Rev Vaccines 2015; 14:1031-41. [PMID: 25882610 DOI: 10.1586/14760584.2015.1037744] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The available vaccines against human papillomavirus have some limitations such as low coverage due to their high cost, reduced immune coverage and the lack of therapeutic effects. Recombinant vaccines produced in plants (genetically engineered using stable or transient expression systems) offer the possibility to obtain low cost, efficacious and easy to administer vaccines. The status on the development of plant-based vaccines against human papillomavirus is analyzed and placed in perspective in this review. Some candidates have been characterized at a preclinical level with interesting outcomes. However, there is a need to perform the immunological characterization of several vaccine prototypes, especially through the oral administration route, as well as develop new candidates based on new chimeric designs intended to provide broader immunoprotection and therapeutic activity.
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Affiliation(s)
- Sergio Rosales-Mendoza
- Laboratorio de Biofarmacéuticos Recombinantes, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, SLP, 78210, México, USA
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D'Hauwers KWM, Gadet PFE, Donders ART, Tjalma WAA. Impact of medical education on knowledge and attitudes regarding the human papilloma virus and vaccination: comparison before and 6 years after the introduction of the vaccines. Vaccine 2013; 31:5843-7. [PMID: 24161571 DOI: 10.1016/j.vaccine.2013.09.068] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2013] [Revised: 08/26/2013] [Accepted: 09/30/2013] [Indexed: 11/20/2022]
Abstract
AIM The lifetime risk for acquiring a human papilloma virus (HPV) infection is 80% for sexually active people. High-risk HPVs are causally related to almost every case of cervical cancer, and to a subgroup of vaginal, vulvar, anal, penile and oral/oropharyngeal cancer. Low-risk HPVs are related to cutaneous, anogenital, and oral warts. Two prophylactic vaccines were launched in 2007: they were included in the national vaccination program in Belgium (2009) and in the Netherlands (2010). The objectives of the present study were to determine and compare knowledge and attitudes regarding HPV and vaccination among a study population in 2006 and in 2012. MATERIALS AND METHODS Shortly before the introduction, and three years after the inclusion, 715 (2006) and 678 participants (2012) were questioned. Participants were categorised as into non-medics, medics, or paramedics. RESULTS In general, knowledge about HPV has increased over time (p<0.01). Well-known facts are the relationship of HPV with cervical cancer (>94% in 2006; >96% in 2012), and that an HPV infection might be asymptomatic (>95% in 2006; >99% in 2012). In 2012, versus in 2006, paramedics and non-medics (both p<0.01), were more likely to vaccinate all female teenagers. Medics were less likely to support this (p=0.001). More respondents agreed to vaccinate their daughters (p<0.01), as well as their sons (p<0.01). In 2012, when compared with 2006, less non-medics and medics (both p<0.01) and more paramedics (p=0.001) would accept a free catch-up vaccination. Arguments against catch-up vaccination reflected the belief not being at risk and doubts about the vaccines' safety. CONCLUSION The facts that vaccination programs are regarded as being important, and that knowledge on HPV increased, do not automatically result in an increase in participation in HPV vaccination programs. To increase participation, information must be provided with arguments that cannot be misinterpreted.
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Affiliation(s)
- K W M D'Hauwers
- Radboud University Medical Center, Department of Urology, Route 659, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.
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Li G, Huang Z, Chen X, Wei Q. Role of human papillomavirus and cell cycle-related variants in squamous cell carcinoma of the oropharynx. J Biomed Res 2013; 24:339-46. [PMID: 23554649 PMCID: PMC3596680 DOI: 10.1016/s1674-8301(10)60047-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2010] [Indexed: 12/25/2022] Open
Affiliation(s)
- Guojun Li
- Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4095, USA ; Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4095, USA
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Chen X, Jiang J, Shen H, Hu Z. Genetic susceptibility of cervical cancer. J Biomed Res 2013; 25:155-64. [PMID: 23554684 PMCID: PMC3597058 DOI: 10.1016/s1674-8301(11)60020-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2011] [Revised: 02/21/2011] [Accepted: 03/03/2011] [Indexed: 12/14/2022] Open
Abstract
Epidemiological and laboratory-based studies have identified infection with one of 15 high-risk human papillomavirus (HPV) types as a necessary but not sufficient cause of cervical cancer. The prevalence of genital HPV infections is high in young women, but most of the infections regress without interventions. Host genetic variations in genes involved in immune response pathways may be related to HPV clearance, and HPV E6/E7 oncoproteins interacting or downstream genes, both coding and non-coding, may contribute to the outcome of high risk HPV infection and cervical cancer. Of specific interest for this review has been the selection of genetic variants in genes involved in the above-referred pathways with a summary of their applications in association studies. Because the supportive and opposing data have been reported in different populations, well-designed international collaborative studies need to be conducted to define the consistency of the associations, paving the way to better define the patients at high risk of developing cervical cancer.
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Affiliation(s)
- Xiaojun Chen
- Department of Gynecology, Tumor Hospital of Nantong, Nantong, Jiangsu 226000, China ; Department of Epidemiology and Biostatistics, Nanjing Medical University, Nanjing, Jiangsu 210029, China
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Vidal AC, Murphy SK, Hernandez BY, Vasquez B, Bartlett JA, Oneko O, Mlay P, Obure J, Overcash F, Smith JS, van der Kolk M, Hoyo C. Distribution of HPV genotypes in cervical intraepithelial lesions and cervical cancer in Tanzanian women. Infect Agent Cancer 2011; 6:20. [PMID: 22081870 PMCID: PMC3262746 DOI: 10.1186/1750-9378-6-20] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2011] [Accepted: 11/14/2011] [Indexed: 11/16/2022] Open
Abstract
Background Infection with human papillomavirus (HPV) is associated with uterine cervical intraepithelial neoplasia (CIN) and invasive cancers (ICC). Approximately 80% of ICC cases are diagnosed in under-developed countries. Vaccine development relies on knowledge of HPV genotypes characteristic of LSIL, HSIL and cancer; however, these genotypes remain poorly characterized in many African countries. To contribute to the characterization of HPV genotypes in Northeastern Tanzania, we recruited 215 women from the Reproductive Health Clinic at Kilimanjaro Christian Medical Centre. Cervical scrapes and biopsies were obtained for cytology and HPV DNA detection. Results 79 out of 215 (36.7%) enrolled participants tested positive for HPV DNA, with a large proportion being multiple infections (74%). The prevalence of HPV infection increased with lesion grade (14% in controls, 67% in CIN1 cases and 88% in CIN2-3). Among ICC cases, 89% had detectable HPV. Overall, 31 HPV genotypes were detected; the three most common HPV genotypes among ICC were HPV16, 35 and 45. In addition to these genotypes, co-infection with HPV18, 31, 33, 52, 58, 68 and 82 was found in 91% of ICC. Among women with CIN2-3, HPV53, 58 and 84/83 were the most common. HPV35, 45, 53/58/59 were the most common among CIN1 cases. Conclusions In women with no evidence of cytological abnormalities, the most prevalent genotypes were HPV58 with HPV16, 35, 52, 66 and 73 occurring equally. Although numerical constraints limit inference, findings that 91% of ICC harbor only a small number of HPV genotypes suggests that prevention efforts including vaccine development or adjuvant screening should focus on these genotypes.
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Affiliation(s)
- Adriana C Vidal
- Department of Community and Family Medicine, and Program of Cancer Detection, Prevention and Control, Duke University School of Medicine, Durham, NC, USA.
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Graham JE, Mishra A. Global challenges of implementing human papillomavirus vaccines. Int J Equity Health 2011; 10:27. [PMID: 21718495 PMCID: PMC3143925 DOI: 10.1186/1475-9276-10-27] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2010] [Accepted: 06/30/2011] [Indexed: 12/02/2022] Open
Abstract
Human Papillomavirus vaccines are widely hailed as a sweeping pharmaceutical innovation for the universal benefit of all women. The implementation of the vaccines, however, is far from universal or equitable. Socio-economically marginalized women in emerging and developing, and many advanced economies alike, suffer a disproportionately large burden of cervical cancer. Despite the marketing of Human Papillomavirus vaccines as the solution to cervical cancer, the market authorization (licensing) of the vaccines has not translated into universal equitable access. Vaccine implementation for vulnerable girls and women faces multiple barriers that include high vaccine costs, inadequate delivery infrastructure, and lack of community engagement to generate awareness about cervical cancer and early screening tools. For Human Papillomavirus vaccines to work as a public health solution, the quality-assured delivery of cheaper vaccines must be integrated with strengthened capacity for community-based health education and screening.
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Affiliation(s)
- Janice E Graham
- Department of Bioethics, Dalhousie University, Faculty of Medicine, 1459 Oxford Street, Halifax, Nova Scotia, B3H 4R2, Canada
| | - Amrita Mishra
- Technoscience and Regulation Research Unit, 1459 Oxford Street, Halifax, Nova Scotia, B3H 4R2, Canada
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Sigurdsson K. Cervical cancer: cytological cervical screening in Iceland and implications of HPV vaccines. Cytopathology 2009; 21:213-22. [DOI: 10.1111/j.1365-2303.2010.00783.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Nicol AF, Pires ARC, de Souza SR, Nuovo GJ, Grinsztejn B, Tristão A, Russomano FB, Velasque L, Lapa e Silva JR, Pirmez C. Cell-cycle and suppressor proteins expression in uterine cervix in HIV/HPV co-infection: comparative study by tissue micro-array (TMA). BMC Cancer 2008; 8:289. [PMID: 18840277 PMCID: PMC2577688 DOI: 10.1186/1471-2407-8-289] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2007] [Accepted: 10/07/2008] [Indexed: 11/18/2022] Open
Abstract
Background The oncoproteins of human papillomavirus (HPVs) directly effect cell-cycle control. We hypothesize that regulatory and cell cycle protein expression might be additionally modified in the cervix of HIV/HPV co-infected women. Methods We analyzed the expression of Rb, p27, VEGF and Elf-1 transcriptor factor by immunohistochemistry in 163 paraffin-embeded cervical samples using Tissue Micro-Array (TMA) and correlated this to HIV-1 and HPV infection. Results HIV/HPV co-infection was associated with a significant increase in expression (p < 0.001) of VEGF and p27 in both low and high grade CIN when compared to the cervices of women infected by HPV alone. Decreased Rb expression was evident with increased CIN grade in the cervices of women infected with HPV alone (p = 0.003 average of cells/mm2 in CIN I: 17.9, CIN II/III: 4.8, and tumor 3.9). Rb expression increased 3-fold for both low and high grade CIN with HPV/HIV-1 co-infection compared to HPV infection alone but did not reach statistical significance. There was a significant increase in Elf-1 expression in HPV+/HIV- women with CIN II/III and tumor (average of cells/mm2 in CIN I: 63.8; CIN II/III: 115.7 and tumor: 112.0, p = 0.005), in comparison to controls. Conclusion Co-infection of HPV and HIV leads to significant increase in the VEGF and p27 expression when compared to HPV+/HIV-negative infection that could facilitate viral persistence and invasive tumor development.
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Affiliation(s)
- Alcina F Nicol
- Laboratory of Immunopathology, Instituto Oswaldo Cruz - FIOCRUZ, Rio de Janeiro, Brazil.
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Mosavel M, El-Shaarawi N. "I have never heard that one": young girls' knowledge and perception of cervical cancer. JOURNAL OF HEALTH COMMUNICATION 2007; 12:707-719. [PMID: 18030637 DOI: 10.1080/10810730701671985] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
With the advent of a vaccine for the human papillomavirus (HPV), many are claiming that cervical cancer may become a health worry of the past. While the vaccine certainly represents an important step forward in the fight against HPV and cervical cancer, it does not diminish the importance of health education or screening interventions particularly amongst adolescents. This study explores the existing state of cancer and cervical cancer knowledge of Latina and African American adolescent girls from low-income, urban neighborhoods. We found that the study participants expressed a range of attitudes toward cancer. Knowledge of cancer also was varied and somewhat anecdotal, showing no unified body of knowledge, but instead representing an assemblage of information culled from formal and informal sources. Participants were most familiar with breast and lung cancer and mentioned these types of cancer most frequently in the focus groups. Most participants had never heard of cervical cancer, while a few were familiar with several aspects of the disease. Cancer knowledge seemed to be gleaned mostly from personal stories, perhaps suggesting the pervasiveness of cancer incidence in their community. The predominant attitudes expressed toward cancer included fear, uncertainty, and anxiety. Our findings suggest that considerable continued health promotion efforts are needed to improve knowledge about cancer in general, and particularly about cervical cancer, to reduce fear and to highlight the effectiveness of prevention and screening.
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Affiliation(s)
- Maghboeba Mosavel
- Center for Reducing Health Disparities, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.
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11
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Global Stability of Equilibria in a Two-Sex HPV Vaccination Model. Bull Math Biol 2007; 70:894-909. [DOI: 10.1007/s11538-007-9283-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2007] [Accepted: 10/03/2007] [Indexed: 10/22/2022]
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D'Hauwers K, Depuydt C, Bogers JP, Stalpaert M, Vereecken A, Wyndaele JJ, Tjalma W. Urine versus brushed samples in human papillomavirus screening: study in both genders. Asian J Androl 2007; 9:705-10. [PMID: 17712490 DOI: 10.1111/j.1745-7262.2007.00287.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
AIM To investigate whether urine is a good medium for screening and whether there is a correlation between the amount of extracted DNA and human papillomavirus (HPV)-positivity. METHODS In the present study, 30 first-voided urine (FVU) specimens and 20 urethroglandular swabs using cervex-brushes from male partners of HPV-positive patients, and 31 FVU specimens and 100 liquid-based cervix cytology leftovers sampled with cervix-brushes from HPV-positive women were examined for the presence of beta-globin. Oncogenic HPV were detected using type-specific PCR. RESULTS beta-globin was found in all the brushed samples, whereas it was found in only 68.9% of the FVU specimens. HPV-PCR was positive in 60.0% of the male brushes, in 29% of the female brushes and in 0% of the male FVU specimens. DNA concentration was, respectively, 0.9998 ng/microL, 37.0598 ng/microL and 0.0207 ng/microL. CONCLUSION Urine is not a good tool for HPV detection, probably because the low DNA concentration reflects a low amount of collected cells. beta-globin is measurable in FVU by real time quantitative PCR, but the DNA concentration is lower compared to brush sampling for both genders. beta-globin-positivity of urethral and cervical swabs is 100%, showing a higher mean concentration of DNA, leading to a higher detection rate of HPV. This is the first article linking DNA-concentration to the presence of HPV.
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Affiliation(s)
- Kathleen D'Hauwers
- Department of Urology, University Hospital Antwerp, Antwerp, Belgium. K.D'
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Arbyn M, Dillner J. Review of current knowledge on HPV vaccination: An Appendix to the European Guidelines for Quality Assurance in Cervical Cancer Screening. J Clin Virol 2007; 38:189-97. [PMID: 17258503 DOI: 10.1016/j.jcv.2006.12.009] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2006] [Revised: 11/28/2006] [Accepted: 12/07/2006] [Indexed: 11/23/2022]
Abstract
The recognition of a strong etiological relationship between infection with high-risk human papillomavirusses and cervical cancer has prompted research to develop and evaluate prophylactic and therapeutic vaccines. One prophylactic quadrivalent vaccine using L1 virus-like particles (VLP) of HPV 6, 11, 16 and 18 is available on the European market since the end of 2006 and it is expected that a second bivalent vaccine containing VLPs of HPV16 and HPV18 will become available in 2007. Each year, HPV16 and HPV18 cause approximately 43,000 cases of cervical cancer in the European continent. Results from the phase-IIb and III trials published thus far indicate that the L1 VLP HPV vaccine is safe and well-tolerated. It offers HPV-naive women a very high level of protection against HPV persistent infection and cervical intra-epithelial lesions associated with the types included in the vaccine. HPV vaccination should be offered to girls before onset of sexual activity. While prophylactic vaccination is likely to provide important future health gains, cervical screening will need to be continued for the whole generation of women that is already infected with the HPV types included in the vaccine. Phase IV studies are needed to demonstrate protection against cervical cancer and to verify duration of protection, occurrence of replacement by non-vaccine types and to define future policies for screening of vaccinated cohorts. The European Guidelines on Quality Assurance for Cervical Cancer Screening provides guidance for secondary prevention by detection and management of precursors lesions of the cervix. The purpose of the appendix on vaccination is to present current knowledge. Developing guidelines for future use of HPV vaccines in Europe, is the object of a new grant offered by the European Commission.
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Affiliation(s)
- Marc Arbyn
- Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium.
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Sigurdsson K, Taddeo FJ, Benediktsdottir KR, Olafsdottir K, Sigvaldason H, Oddsson K, Rafnar T. HPV genotypes in CIN 2-3 lesions and cervical cancer: A population-based study. Int J Cancer 2007; 121:2682-7. [PMID: 17724723 DOI: 10.1002/ijc.23034] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The distribution of human papillomavirus (HPV) varies between countries and continents leading to different effectiveness of upcoming prophylactic HPV vaccines. This study analyses the HPV distribution in CIN 2-3, recurrent CIN 2-3 and cervical cancer in Iceland. About 80% of incident cases with CIN 2-3 lesions in 1990 and 1999, 99% of cancer cases in 1990-1994 and 1999-2003, and cases with recurrent CIN 2-3 after conization in 1990 were tested with PCR analysis for the presence of 12 oncogenic HPV types. About 95% of the CIN 2-3 and 92% of the cancer cases tested positive for the included HPV types. HPV 16 was the most frequent type followed by HPV 33, 31, 52, 35, 18, 58, 56, 39, 45, 59 in CIN 2-3 and by HPV 18, 33 45, 31, 39, 52, 35, 51, 56 in cancer. HPV 16 and 18 were associated with a significantly increased cancer risk and HPV 52 and 31 with decreased cancer risk compared to the risk of CIN 3. The HPV distribution differed between histological cancer types, stages and age groups. The number of HPV types was not a significant predictor of cancer. Oncogenic HPV types were found in all persistent or recurrent CIN 2-3 disease after conization. Vaccination against HPV 16/18 is estimated to achieve a minimum 40% reduced rate of CIN 2-3 and a minimum 60% reduced cancer rate. This rate could, however, be increased to 95% and 92% respectively by including all the 12 HPV types tested for in this study.
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Affiliation(s)
- Kristjan Sigurdsson
- The Icelandic Cancer Detection Clinic, Icelandic Cancer Society, Reykjavik, Iceland.
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Affiliation(s)
- W A A Tjalma
- Department of Gynecology and Gynaecological Oncology, University Hospital Antwerpen, Edegem, Belgium.
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Kelloff GJ, Lippman SM, Dannenberg AJ, Sigman CC, Pearce HL, Reid BJ, Szabo E, Jordan VC, Spitz MR, Mills GB, Papadimitrakopoulou VA, Lotan R, Aggarwal BB, Bresalier RS, Kim J, Arun B, Lu KH, Thomas ME, Rhodes HE, Brewer MA, Follen M, Shin DM, Parnes HL, Siegfried JM, Evans AA, Blot WJ, Chow WH, Blount PL, Maley CC, Wang KK, Lam S, Lee JJ, Dubinett SM, Engstrom PF, Meyskens FL, O'Shaughnessy J, Hawk ET, Levin B, Nelson WG, Hong WK. Progress in chemoprevention drug development: the promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer--a plan to move forward. Clin Cancer Res 2006; 12:3661-97. [PMID: 16778094 DOI: 10.1158/1078-0432.ccr-06-1104] [Citation(s) in RCA: 188] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
This article reviews progress in chemopreventive drug development, especially data and concepts that are new since the 2002 AACR report on treatment and prevention of intraepithelial neoplasia. Molecular biomarker expressions involved in mechanisms of carcinogenesis and genetic progression models of intraepithelial neoplasia are discussed and analyzed for how they can inform mechanism-based, molecularly targeted drug development as well as risk stratification, cohort selection, and end-point selection for clinical trials. We outline the concept of augmenting the risk, mechanistic, and disease data from histopathologic intraepithelial neoplasia assessments with molecular biomarker data. Updates of work in 10 clinical target organ sites include new data on molecular progression, significant completed trials, new agents of interest, and promising directions for future clinical studies. This overview concludes with strategies for accelerating chemopreventive drug development, such as integrating the best science into chemopreventive strategies and regulatory policy, providing incentives for industry to accelerate preventive drugs, fostering multisector cooperation in sharing clinical samples and data, and creating public-private partnerships to foster new regulatory policies and public education.
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Affiliation(s)
- Gary J Kelloff
- National Cancer Institute, Bethesda, Maryland 20852, USA.
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Tjalma WAA. Cervical cancer and prevention by vaccination: results from recent trials. Ann Oncol 2006; 17 Suppl 10:x217-23. [PMID: 17018727 DOI: 10.1093/annonc/mdl263] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- W A A Tjalma
- Department of Gynecology and Gynecologic Oncology, University Hospital Antwerpen, Edegem, Belgium
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Abstract
Gynecological malignancies remain a major source of morbidity and mortality worldwide. In the USA alone, more than 77,000 women are diagnosed annually and over 28,000 die of some form of a gynecological malignancy. Many of these women will fail conventional therapy, leaving few remaining treatment options. Gene therapy presents one possible alternative treatment modality although, unfortunately, it is currently more theoretical than practical. Here, some of the basic science behind gene therapy is reviewed, different delivery systems used to transport the therapeutic gene are discussed, different methods of achieving a therapeutic effect are examined, some of the key trials in ovarian, endometrial, cervical and vulvar cancer research are highlighted and the future of gene therapy is explored.
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Affiliation(s)
- Rebecca A Brooks
- Department of Obstetrics and Gynecology, Washington University, St. Louis, MO, USA.
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Abstract
Human papillomavirus type-16 infection is associated with a significant portion of squamous carcinoma of the head and neck, particularly for the oropharynx and for those lacking the other risk factors of tobacco and alcohol. The link between human papillomavirus type-16 and carcinoma of the oropharynx is based on the identification of human papillomavirus type-16 in oropharyngeal tumors and the association of human papillomavirus type-16 with the risk of oropharyngeal cancer estimated in case-control epidemiologic studies. This review highlights the molecular mechanism of human papillomavirus carcinogenesis and the association of human papillomavirus type-16 as a risk factor for squamous cell carcinoma of the oropharynx as well as recent research efforts utilizing human papillomavirus as a biomarker of clinical outcomes.
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Affiliation(s)
- Guojun Li
- Department of Head and Neck Surgery, Unit 441, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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De Marco F, Houissa-Kchouk F, Khelifa R, Marcante ML. High-risk HPV types in Tunisia. A pilot study reveals an unexpectedly high prevalence of types 58 and 82 and lack of HPV 18 among female prostitutes. J Med Virol 2006; 78:950-3. [PMID: 16721861 DOI: 10.1002/jmv.20646] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
"High-risk" HPVs (HR-HPV) have sharply different prevalences and there is evidence to suggest this may vary according to regions. Accurate description of HR-HPV circulation is a key feature for the rational design of prevention and screening campaigns. To gain insight into HR-HPV circulation in Tunisia, a pilot study was carried out on 64 healthy prostitutes working in the Tunis area. HPV detection and typing were carried out by MY09/MY11 PCR and restriction fragment length polymorphism (RFLP). A selected set of samples was also assayed by Gp5+/Gp6+ PCR and typed by direct sequencing. Out of 64 women, 28 were HPV positive. HPV-16 and HPV-58, both members of the genus Alpha-Papillomavirus, species 9, accounted for 10 and 7 cases with a prevalence rate of 38% and 27%, respectively. HPV-82, a member of species 5, ranked third with four cases (approximately 15%). Types 31, 33, 35; all members of species 9 were each detected once (approximately 4%) while neither HPV-18 nor related members of species 7 were detected. Type 72 and 83, both members of species 3, were the only low-risk types, each detected only once (4% each). Two samples could not be typed. The prevalence of HPV types appeared sharply different from that of neighboring areas. Should the existence of epidemiological pockets be confirmed by larger, more detailed studies, screening and vaccine campaigns will have to be designed carefully taking into account the actual epidemiological context of the target population.
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22
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The Future Role of Vaccines and Microbicides. Sex Transm Dis 2006. [DOI: 10.1007/978-1-59745-040-9_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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23
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Abstract
Vaccines against the most common human papillomavirus (HPV) types are currently under development. Epidemiologic data suggest that the transmission dynamics of different HPV types are not independent. Some studies indicate that interactions among HPV types are synergistic, where infection with one type facilitates concurrent or subsequent infection with another HPV type. Other studies point to antagonistic interference among HPV types. Here we develop a mathematical model to explore how these interactions may either enhance or diminish the effectiveness of vaccination programs designed to reduce the prevalence of the HPV types associated with cervical cancer. We analyze the local stability of the infection-free and boundary equilibria and characterize the conditions leading to a coexistence equilibrium. We also illustrate the results with numerical simulations using realistic model parameters. We show that if interactions among HPV types are synergistic, mass vaccination may reduce the prevalence of types that are not even included in the vaccine.
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Affiliation(s)
- Elamin H Elbasha
- Merck Research Laboratories, 10 Sentry Parkway, BL 2-3, Blue Bell, PA 19422, United States.
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24
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Bodurka DC. What's new in gynecology and obstetrics. J Am Coll Surg 2005; 201:265-74. [PMID: 16038826 DOI: 10.1016/j.jamcollsurg.2005.05.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2005] [Accepted: 05/13/2005] [Indexed: 11/28/2022]
Affiliation(s)
- Diane C Bodurka
- Department of Gynecologic Oncology, MD Anderson Cancer Center, Houston, TX 77230-1439, USA
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25
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Tjalma WAA, Van Damme P. Is the public enough aware to accept a vaccination program against human papillomavirus? Vaccine 2005; 23:3231. [PMID: 15837225 DOI: 10.1016/j.vaccine.2005.01.143] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2004] [Indexed: 11/26/2022]
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26
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Malinowski DP. Molecular diagnostic assays for cervical neoplasia: emerging markers for the detection of high-grade cervical disease. Biotechniques 2005; Suppl:17-23. [PMID: 16528919 DOI: 10.2144/05384su03] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
The accurate detection and diagnosis of cervical carcinoma and its malignant precursors (collectively referred to as high-grade cervical disease) represents one of the current challenges in clinical medicine and cytopathology. The advent of molecular diagnostics and the use of whole-genome profiling using DNA microarrays promises to yield improved understanding of the disease process with the subsequent development of more accurate diagnostic procedures based upon these discoveries. Recent reports describing a variety of experimental approaches have identified a series of candidate genes that are overexpressed in cervical carcinoma. In this article, representative examples of these markers and the resulting translational research will be reviewed within the context of improved cervical disease detection. An emerging class of markers, the minichromosome maintenance protein family of DNA licensing factors (MCM-2, MCM-6, MCM-7), shows promise for the specific detection of high-grade cervical disease using simple antibody-based immunochemistry formats. These proteins are overexpressed in cervical disease as a result of infection by oncogenic strains of human papillomavirus (HPV) and subsequent uncontrolled activation of gene transcription and aberrant S-phase induction, mediated through the E2F transcription factor pathway. This behavior appears to be a hallmark of high-grade cervical disease and provides the link between oncogenic HPV infections and the molecular behavior of cervical neoplasia (CN). The use of these molecular descriptors of CN in simple immunochemistry formats compatible with conventional cytology preparations is anticipated to improve the screening and detection of cervical disease within the healthcare system.
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Tjalma WAA, Van Waes TR, Van den Eeden LEM, Bogers JJPM. Role of human papillomavirus in the carcinogenesis of squamous cell carcinoma and adenocarcinoma of the cervix. Best Pract Res Clin Obstet Gynaecol 2005; 19:469-83. [PMID: 16150388 DOI: 10.1016/j.bpobgyn.2005.02.002] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Human papillomavirus (HPV) infection is the most common sexually transmitted disease, with more than 80% of the population infected at some time in their life. In rare cases, this infection may lead to cervical cancer. Virtually all squamous cell carcinomas and the overwhelming majority of adenocarcinomas of the cervix are HPV positive. HPV integration in the genome will lead to inactivation of the p53 pathway and the Rb pathway. Integration is essential for the onset of cervical carcinogenesis, but is probably not sufficient for progression to invasive cervical cancers. It is likely that several cofactors, such as environmental, viral and host-related factors, are necessary for the development of cervical cancer. There are several similarities and differences between the two major histological types. This article will address the role of HPV in cervical carcinogenesis as well as the molecular biology involved in the process.
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Affiliation(s)
- W A A Tjalma
- Department of Gynecology and Gynecologic Oncology, University Hospital Antwerpen, Universiteit Antwerpen, Wilrijkstraat 10, 2650 Antwerp, Belgium.
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