How will HPV vaccines affect cervical cancer?

Abstract

Cancer of the uterine cervix is the second largest cause of cancer deaths in women, and its toll is greatest in populations that lack screening programmes to detect precursor lesions. Persistent infection with 'high risk' genotypes of human papillomavirus (HPV) is necessary, although not sufficient, to cause cervical carcinoma. Therefore, HPV vaccination provides an opportunity to profoundly affect cervical cancer incidence worldwide. A recently licensed HPV subunit vaccine protects women from a high proportion of precursor lesions of cervical carcinoma and most genital warts. Here we examine the ramifications and remaining questions that surround preventive HPV vaccines.Epidemiological and laboratory studies overwhelmingly support a necessary role for persistent human papillomavirus (HPV) infection and transcription in cervical carcinogenesis 1,2 (BOX 1). Importantly, HPV infection alone is not sufficient for cervical carcinogenesis, and additional steps occur over one or two decades. HPV is probably the most common sexually transmitted disease. It is estimated that the worldwide agestandardized prevalence of current HPV infection is 10.5% (95% CI 9.9-11.0) of women; the prevalence varies about 20-fold between different regions, from 1.4% (95% CI 0.5-2.2) in Spain to , although adenocarcinomas of the cervix are more challenging to detect with this approach. Progression to cancer can usually be prevented by the ablation or surgical removal of high-grade precursor lesions (HSIL or CIN2/3). In 2005, more than 60 million Pap smears were performed in the United States, and it is estimated that such screening programmes and intervention have reduced the incidence of cervical cancer by ~80% in the United States, but at a cost of more than US$6 billion a year.Despite this success, many women do not have access to screening. This problem is most acute in disadvantaged minorities in developed nations, in cultures that do not accept the screening process and in countries that are remote and lack the resources for screening programmes. Consequently, the impact of cervical cancer is greatest in these countries; the latest global estimates (from 2002) are 493,000 new cervical cancer cases each year, and 274,000 deaths, 80% of which occur in developing countries 8 .Vaccination traditionally represents the most cost-effective approach to combat infectious disease. Two approaches to vaccination, or a combination of both, can be considered: prophylactic (preventive) and therapeutic immunization. Prophylactic vaccination of healthy individuals against the aetiological agent protects against acquisition of the disease, but confers some risk to otherwise healthy patients and requires massive programmes to vaccinate a significant fraction of the population. Comprehensive prophylactic vaccination has historically proven most successful in disease reduction. The US Food and Drug Administration (FDA) approved a preventive HPV vaccine on 8 June 2006 for the immunization of women between 9-26 years of age 9 , and a second vacci...

Cervical cancer in Bangladesh: community perceptions of cervical cancer and cervical cancer screening

“…Hence, implementation in developing countries may not be realistic until a cheaper and more practical vaccine (i.e. inhalation or transdermal alternatives) are available (Roden and Wu 2006).…”

Immunochemical analysis of HPV L1 capsid protein and p16 protein in liquid-based cytology samples from uterine cervical lesions

“…The progression of untreated lesions to microinvasive and overtly invasive cancers is associated with integration of the HPV genome into the host chromosomes. 3 Persistent cervical infection and integration with an oncogenic HPVs, such as HPV 16 and HPV 18, are the most important risk factors for progression of LSILs to HSILs or SCCs. 4 The number of cases of malignant disease of the cervix is, however, small compared with the number of women infected with HPV.…”

“…These virions shed the virus, which then reinitiates infection. 3 Therefore, the productive phase refers to the early stage of HPV infection with L1 capsid protein expression. In contrast, the second phase is the ''transformation'' phase, in which HPV DNA is integrated into the host DNA.…”

Role of HPV Vaccination in Fighting Cervical Cancer

“…Even in a high-income country like Hong Kong(China), the high price of HPV vaccines is still a major barrier (4) . With the help of the World Health Organizations and The Global Alliance for Vaccines and Immunization (GAVI), a new hope has been given to provide a more affordable and equal distribution of HPV vaccines, especially in low and middle-income countries (30) . One strategy to reduce cost as discussed before is by reducing the dose from three-dose to twodose, with no change in immunogenicity (10) .…”