Institute Catala Doncologia Catalan Institute Of Oncology Ico Lhospitalet Of Llobregat

Barcelona, Spain

Institute Catala Doncologia Catalan Institute Of Oncology Ico Lhospitalet Of Llobregat

Barcelona, Spain

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Franco E.L.,McGill University | de Sanjose S.,Institute Catala Doncologia Catalan Institute Of Oncology Ico Lhospitalet Of Llobregat | de Sanjose S.,CIBER ISCIII | Broker T.R.,University of Alabama at Birmingham | And 4 more authors.
Vaccine | Year: 2012

The recognition that human papillomavirus (HPV) infection is the central, necessary cause of cervical cancer paved the way to new fronts of prevention via improved screening methods and HPV vaccination. Much has been learned in all fronts, from the molecular basis of our understanding of how HPV causes disease to the health economics of preventive strategies at the individual and population levels. Progress in other areas of cancer control has yet to show the same multi- and trans-disciplinary gains seen in research on HPV-associated malignancies, which is one of the unequivocal success stories in disease prevention. Yet, as an embarrassment of riches, much more research is needed to fill the gaps in knowledge that remain before we are able to reap the benefits from the knowledge translation from all fronts. Public health research on setting-specific implementation of HPV-based preventive strategies and more concerted advocacy to counter barriers facing the adoption of these strategies are likely to yield major dividends in reducing the burden of HPV-associated diseases. © 2012 Elsevier Ltd.


Gillison M.L.,Ohio State University | Alemany L.,Institute Catala Doncologia Catalan Institute Of Oncology Ico Lhospitalet Of Llobregat | Alemany L.,CIBER ISCIII | Snijders P.J.F.,VU University Amsterdam | And 5 more authors.
Vaccine | Year: 2012

Human papillomavirus (HPV) infection is causally associated with benign and malignant diseases of the upper airway, including respiratory papillomatosis and oropharyngeal cancer. Low-risk HPV types 6 and 11 are the predominant cause of papillomatosis, whereas only HPV16 definitively satisfies both molecular and epidemiological causal criteria as a carcinogenic or high-risk type in the upper airway. HPV16 E6/E7 mRNA expression and integration are observed predominantly among oropharyngeal cancers, and experimental models have shown E6/E7 expression to be necessary for the initiation and maintenance of the malignant phenotype of these cancers. From an epidemiological perspective, a strong and consistent association between markers of HPV16 exposure and oropharyngeal cancer has been demonstrated in numerous case-control studies. HPV-positive oropharyngeal cancers have also been shown to be distinct from HPV-negative head and neck squamous cell cancers with regard to risk-factor profiles, molecular genetic alterations, population-level incidence trends over time, and prognosis. Tumor HPV status (as determined by certain HPV16 in situ hybridization assays or certain p16 immunohistochemistry assays) is the strongest determinant of survival for patients with local-regionally advanced oropharyngeal cancer: patients with HPV-positive cancer have at least a 50% improvement in overall survival at 5 years, which is equivalent to an approximate 30% difference in absolute survival. Thus, HPV status determination is now part of the routine diagnostic evaluation for prognostication. Preliminary evidence indicates that a small proportion of head and neck cancers may be caused by additional HPV types (e.g., 18, 31, 33, 35) and that HPV-caused cancers may rarely arise from non-oropharyngeal sites (e.g., the oral cavity, nasopharynx, and larynx). Whether or not HPV vaccination has the potential to prevent oral HPV infections that lead to cancer or papillomatosis in the upper airway is currently unknown, as is the potential for secondary prevention with HPV detection. © 2012 Published by Elsevier Ltd.


Denny L.A.,University of Cape Town | Franceschi S.,International Agency for Research on Cancer | de Sanjose S.,Institute Catala Doncologia Catalan Institute Of Oncology Ico Lhospitalet Of Llobregat | de Sanjose S.,CIBER ISCIII | And 3 more authors.
Vaccine | Year: 2012

The vast majority of women infected with human immunodeficiency virus (HIV) will be co-infected with human papillomavirus (HPV). The interaction between the two sexually transmitted infections appears to be related to the alteration in cell-mediated immunity in HIV infected persons, increased susceptibility, and possibly reactivation of latent HPV infection. Linkage studies of HIV/AIDs and Cancer registries have indicated a 2- to 22-fold increase in cervical cancer in HIV-positive women compared to HIV-negative women. Data on the prevalence of HPV types in invasive cervical carcinoma (ICC) suggest that the proportion of infection with types HPV16/18 (responsible for over 70% of all cervical cancers) is similar in HIV-negative and HIV-positive women. The biological interaction between HIV and HPV needs further elucidation, although there is some evidence that the presence of HPV infection may be associated with increased HIV transmission. Adolescents perinatally infected by HIV are known to have higher rates of HPV infection and also have been shown to seroconvert in response to HPV vaccination with the quadrivalent vaccine, albeit to lower titers than HIV-negative individuals. Anal cancer incidence is greatly increased in HIV-positive individuals, particularly in HIV-positive men who have sex with men. Screening for anal cancer precursors is feasible and effective; however, the impact on reduction of anal cancer remains to be demonstrated. There are ongoing studies on the safety, immunogenicity, and efficacy of current HPV vaccines in HIV-positive individuals and mature data are awaited. Male circumcision may be another approach to prevention of HPV transmission, which also requires further study. © 2012 Elsevier Ltd.


Castle P.E.,American Society for Clinical Pathology | de Sanjose S.,Institute Catala Doncologia Catalan Institute Of Oncology Ico Lhospitalet Of Llobregat | de Sanjose S.,CIBER ISCIII | Qiao Y.-L.,Peking Union Medical College | And 3 more authors.
Vaccine | Year: 2012

The discovery of the necessary cause of cervical cancer, human papillomavirus (HPV), has led to important technological advances, including the development of molecular tests for HPV to identify women with cervical precancerous lesions. HPV testing has proven to be more sensitive and more reliable, albeit less specific, for detection of cervical precancer than cytologic methods of detection. As the result, HPV testing can reduce the incidence of cervical cancer within 4-5 years and reduce the mortality due to cervical cancer within 8 years compared to cytology. Additionally, a negative HPV test provides greater reassurance against cervical cancer than a negative Pap test. HPV testing, because of its attributes, is useful for screening out low-risk women who do not need further intervention for 5 or more years. Thus, HPV testing can shift the emphasis of the use of Pap testing or any other more specific diagnostic test from frequent use in the entire population to the ̃10% subset of women who tested positive for the causal factor, HPV. Here, we highlight the current and future status of the introduction of HPV testing into routine cervical cancer screening. © 2012 Published by Elsevier Ltd.


Bosch F.X.,Institute Catala Doncologia Catalan Institute Of Oncology Ico Lhospitalet Of Llobregat | Tsu V.,PATH | Vorsters A.,University of Antwerp | Van Damme P.,University of Antwerp | Kane A.M.,Consultant on Immunization Policy
Vaccine | Year: 2012

The reframed paradigm of cervical cancer prevention will include strategic combinations of at least four major components: 1) routine introduction of human papillomavirus (HPV) vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. On a global scale, vaccination of newborns and infants is well established and has developed a successful working infrastructure. The hepatitis B virus (HBV) vaccination programs offer a model for HPV introduction in which newborn and infant immunization achieves a rapid reduction in the prevalence of the HBV carrier rates in immunized cohorts of children, and of liver cirrhosis and liver cancer decades later. In contrast, screening for cervical pre-cancer is largely restricted to industrialized populations and upper social classes in developing countries. The expertise gained by vaccination programs worldwide needs to be coordinated with the traditional cervical cancer prevention community of gynecologists and pathologists. Significant political and advocacy efforts at the Global level (World Health Organization, other United Nations agencies and The GAVI Alliance) need to be organized and reinforced to achieve a meaningful reduction in HPV transmission and its related health conditions and cancers. This desirable goal is now scientifically and technologically attainable, and great progress is being made in obtaining financing for global HPV immunization. © 2012 Elsevier Ltd.


Formana D.,International Agency for Research on Cancer | de Martel C.,International Agency for Research on Cancer | Lacey C.J.,University of York | Soerjomatarama I.,International Agency for Research on Cancer | And 7 more authors.
Vaccine | Year: 2012

The worldwide prevalence of infection with human papillomavirus (HPV) in women without cervical abnormalities is 11-12% with higher rates in sub-Saharan Africa (24%), Eastern Europe (21%) and Latin America (16%). The two most prevalent types are HPV16 (3.2%) and HPV18 (1.4%). Prevalence increases in women with cervical pathology in proportion to the severity of the lesion reaching around 90% in women with grade 3 cervical intraepithelial neoplasia and invasive cancer. HPV infection has been identified as a definite human carcinogen for six types of cancer: cervix, penis, vulva, vagina, anus and oropharynx (including the base of the tongue and tonsils). Estimates of the incidence of these cancers for 2008 due to HPV infection have been calculated globally. Of the estimated 12.7 million cancers occurring in 2008, 610,000 (Population Attributable Fraction [PAF] = 4.8%) could be attributed to HPV infection. The PAF varies substantially by geographic region and level of development, increasing to 6.9% in less developed regions of the world, 14.2% in sub-Saharan Africa and 15.5% in India, compared with 2.1% in more developed regions, 1.6% in Northern America and 1.2% in Australia/New Zealand. Cervical cancer, for which the PAF is estimated to be 100%, accounted for 530,000 (86.9%) of the HPV attributable cases with the other five cancer types accounting for the residual 80,000 cancers. Cervical cancer is the third most common female malignancy and shows a strong association with level of development, rates being at least four-fold higher in countries defined within the low ranking of the Human Development Index (HDI) compared with those in the very high category. Similar disparities are evident for 5-year survival-less than 20% in low HDI countries and more than 65% in very high countries. There are five-fold or greater differences in incidence between world regions. In those countries for which reliable temporal data are available, incidence rates appear to be consistently declining by approximately 2% per annum. There is, however, a lack of information from low HDI countries where screening is less likely to have been successfully implemented. Estimates of the projected incidence of cervical cancer in 2030, based solely on demographic factors, indicate a 2% increase in the global burden of cervical cancer, i.e., in balance with the current rate of decline. Due to the relative small numbers involved, it is difficult to discern temporal trends for the other cancers associated with HPV infection. Genital warts represent a sexually transmitted benign condition caused by HPV infection, especially HPV6 and HPV11. Reliable surveillance figures are difficult to obtain but data from developed countries indicate an annual incidence of 0.1 to 0.2% with a peak occurring at teenage and young adult ages. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. © 2012 Elsevier Ltd. All rights reserved.

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