Cervical Cancer Deaths Research Articles

HPV-vaccination for the prevention of cervical cancer in Austria: a model based long-term prognosis of cancer epidemiology

AimCervical cancer incidence and mortality have decreased for the last 20 years in Austria; however, they remain relatively high in comparison to other European countries. Screening quality has been suboptimal. In this paper we aim to predict the population-wide long-term effects on cervical cancer morbidity and mortality after introducing an HPV vaccination for 12-year-old girls (and boys) in addition to current screening in comparison with screening only.MethodsHealth effects are predicted by a dynamic transmission model that was previously applied in the UK and the Norwegian contexts and validated for Austria. Outcomes analyzed are restricted to cervical cancer mortality and morbidity, which are predicted until 2060 assuming a coverage rate between 65% and 85%, a duration of protection between 10 years and lifelong, and a vaccine efficacy between 80% and 100% in the base case and best case, respectively. Additionally, implications for cancer epidemiology until 2088 are estimated.ResultsCompared to screening only, screening plus vaccination of 12-year-old girls (and boys) would result in a median reduction of 10% (15%) fewer new cancer cases and 13% (20%) fewer cervical cancer deaths under best case assumptions over 52 years in the overall female population. In 2060, female population-based incidence and mortality would decrease by 27% and 43%, respectively, when vaccinating girls only and by 37% and 45% when additionally vaccinating boys. After 2060, a continuous further decrease in incidence and mortality can be expected with a maximum of minus 43% and 53%, respectively, in 2088 when vaccinating girls only.ConclusionAlthough a constant decrease in cervical cancer incidence and mortality is to be expected after introducing a population-wide HPV vaccination program in Austria, the reduction predicted by this model is lower than expected from clinical trials. This is due to several factors, such as low coverage rate and the long time horizon required for generating the maximum benefit of the vaccination in the overall population. In the context of limited resources, for further reducing cervical cancer in Austria, HPV vaccination programs need to be weighed against other public health alternatives such as improving screening quality.

Cost-effectiveness analysis of a cervical cancer vaccine in five Latin American countries

Implementation of cervical cancer (CC) vaccination in Latin America is expected to reduce the high CC burden in those countries. But the efficiency of such vaccination programs in the region still remains unknown. This study assesses the cost-effectiveness and cost-utility of introducing vaccination into the current CC disease management of five Latin American countries (Argentina, Brazil, Chile, Mexico, and Peru). The modelling results indicate that universal mass vaccination is cost-effective in the current health care setting of each country (<3× gross domestic product per capita, per country) with a substantial number of CC cases and deaths avoided in addition to an increase of quality-adjusted life years. This study will help guide the design of future clinical programmes and health-related policies. It will assist early and effective decision-making processes related to vaccine implementation in Latin America.

University Contributions to the HPV Vaccine and Implications for Access to Vaccines in Developing Countries: Addressing Materials and Know-How in University Technology Transfer Policy

Human Papillomavirus (HPV) is a major cause of morbidity and mortality worldwide, with most of the disease burden concentrated in developing countries. Over 90 percent of cervical cancer deaths, almost all of which are caused by HPV, occur in low- and middle-income countries where access to goods and services for prevention and treatment pose major barriers to intervention. In resource-poor settings lacking the capacity for routine screening for cervical cancer, the HPV vaccines developed by Merck and GlaxoSmithKline are desperately needed to help prevent these unnecessary deaths. The initial development of currently available HPV vaccines took place at a number of universities and other publicly funded institutions, yet there is little low-cost access to the vaccine in developing countries where access would be most critical. This is the rule rather than the exception with most university-discovered medicines. Universities and other publicly-funded institutions can adopt a number of licensing methods to ensure that vaccines discovered on their campuses are available at low-cost in developing countries. Universities Allied for Essential Medicines has proposed that universities adopt Global Access Licensing policies to implement these changes by enabling generic or low-cost production of the end product in developing countries. Generic competition is a critical market force that has, for instance, driven down the price of HIV/AIDS treatments from more than $10,000 to less than $99 per patient per year today. While the central barrier to creation of small molecule generics is patent-protection, there are multiple additional barriers that need to be addressed in order to ensure the efficient production of cost-effective generic vaccines and other biologics. While certain biologics may require generic producers to perform additional clinical trials, vaccines are in a somewhat unique situation with respect to both safety and efficacy. With access to appropriate patents, materials and knowledge, vaccines have the potential to be evaluated efficiently and cost-effectively via a pathway parallel to establishing bioequivalence for generic small molecule drugs. A new paradigm is needed that addresses the additional barriers that exist, outside of simply patent protection, to the generic production of vaccines and other biologics. One possible framework, which builds upon previous work on prize funds and patent pools, is discussed here: a Patents, Materials, and Know-how Pool (PMK Pool), based on the patent pool model such as those outlined in the Essential Medical Inventions Licensing Agency and proposals recently put forth by the governments of Barbados and Bolivia. University approaches to licensing vaccines and other biologics need to ensure access not only to patents, knowledge, and materials covered by intellectual property, but must also address the problem of access to materials and know-how that are often proprietary trade secrets. Universities should actively participate in the creation of this and other novel mechanisms, and in the meantime use currently available technology transfer mechanisms to ensure low-cost access to medicines in developing countries.

Mesenchymal Stem Cell Delivery of TRAIL Can Eliminate Metastatic Cancer

Cancer is a leading cause of mortality throughout the world and new treatments are urgently needed. Recent studies suggest that bone marrow-derived mesenchymal stem cells (MSC) home to and incorporate within tumor tissue. We hypothesized that MSCs engineered to produce and deliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a transmembrane protein that causes selective apoptosis of tumor cells, would home to and kill cancer cells in a lung metastatic cancer model. Human MSCs were transduced with TRAIL and the IRES-eGFP reporter gene under the control of a tetracycline promoter using a lentiviral vector. Transduced and activated MSCs caused lung (A549), breast (MDAMB231), squamous (H357), and cervical (Hela) cancer cell apoptosis and death in coculture experiments. Subcutaneous xenograft experiments confirmed that directly delivered TRAIL-expressing MSCs were able to significantly reduce tumor growth [0.12 cm(3) (0.04-0.21) versus 0.66 cm(3) (0.21-1.11); P < 0.001]. We then found, using a pulmonary metastasis model, systemically delivered MSCs localized to lung metastases and the controlled local delivery of TRAIL completely cleared the metastatic disease in 38% of mice compared with 0% of controls (P < 0.05). This is the first study to show a significant reduction in metastatic tumor burden with frequent eradication of metastases using inducible TRAIL-expressing MSCs. This has a wide potential therapeutic role, which includes the treatment of both primary tumors and their metastases, possibly as an adjuvant therapy in clearing micrometastatic disease following primary tumor resection.

Developing vaccines against minor capsid antigen L2 to prevent papillomavirus infection

A subset of human papillomavirus (HPV) genotypes is responsible for approximately 5% of all cancer deaths globally, and uterine cervical carcinoma accounts for the majority of these cases. The impact of HPV is greatest for women who do not have access to effective secondary preventive measures, and consequently over 80% of cervical cancer deaths worldwide occur in developing nations. The understanding that persistent infection by this 'oncogenic' subset of HPV genotypes is necessary for the development of cervical carcinoma has driven the development of preventive vaccines. Two preventive vaccines comprising recombinant HPV L1 virus-like particles (VLPs) have been licensed. However, the current cost of these vaccines precludes sustained global delivery, and they target only two of the approximately 15 known oncogenic HPV types, although approximately 70% of cervical cancer cases are attributed to these two types and there is evidence for some degree of cross-protection against other closely related types. A possible approach to broader immunity at lower cost is to consider vaccination against L2. L2 vaccines can be produced inexpensively and they also have the promise of conferring much broader cross-type protective immunity than that observed with L1 VLP immunization. However, L2 vaccine development lags behind L1 VLP vaccines and several technical hurdles remain.

Worldwide Impact of the Human Papillomavirus Vaccine

Nearly 500,000 new cases of cervical cancer and 274,000 cervical cancer deaths are occurring worldwide each year. Approximately 80% of the 500,000 new cases occur in developing countries and this percentage is expected to increase to 90% by 2020. In developing countries, cervical cancer tends to affect relatively young poor women and is the single largest cause of years of life lost to cancer, since screening and treatment programs, and health care, in general, are relatively inaccessible to these women. Each 5-year delay in vaccinating women against HPV may lead to the deaths of 1.5 to 2 million women from cervical cancer in developing countries. The high efficacy of the two available cervical cancer vaccines and their proven ability to reduce the incidence of cervical cancer precursor lesions offer hope that the vaccine will have enormous worldwide impact and may dramatically reduce the cervical cancer burden. The current vaccines protecting against HPV-16 and HPV-18 may prevent up to 70% of new cervical cancers. Vaccine cross-reactivity for HPV-31, -33, -45, and -52 suggest that an even higher percentage of cervical cancers might be prevented with its use. Currently, the prohibitive cost of the vaccine precludes its widespread implementation. Cooperation between governments, international health organizations, and the vaccine industry is needed to overcome this significant barrier so that women are no longer denied a potentially life-saving advance. Worldwide HPV vaccination and cervical cancer screening should be made an international priority.

Cervical Dysplasia Among Women Over 35 Years of Age

The marked reduction in cervical cancer deaths in the United States is due to early identification of high-grade cervical intraepithelial neoplasia (CIN) 2/3, which is generally accepted as the histologic precursor for development of cervical cancer. Some investigators believe that the risk of CIN 2/3 among women between 35 and 50 years of age is less than among younger women, but this is unproven. In postmenopausal women presenting with cytologic abnormalities, there are conflicting data on the risk of dysplasia compared with younger women; some investigators reported increased risk, and others have found a similar or decreased risk. This retrospective study examined cytologic and histopathologic features among two groups of women with cervical dysplasia who presented to a university referral colposcopy center between 2001 and 2005: premenopausal women aged 35 to 49 years and postmenopausal women aged 50 years or more. The categories of cytologic abnormality referred for colposcopic evaluation included atypical cells of undetermined significance (ASC), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL). A loop electrical excisional procedure (LEEP) was performed in all patients referred with HSIL cytology not explained by colposcopy. Of the 359 patients aged 35 years or older identified, 270 were premenopausal and 89 were postmenopausal. The referral cytology of premenopausal and postmenopausal women was similar with ASC/LSIL in 60% and 65% and HSIL in 35% and 27%, respectively. Postmenopausal women were more likely than premenopausal women to have CIN 3 (41% versus 29%; P < 0.027) and more malignancy (17 versus 0%; P < 0.002). With LEEP, CIN 2 or greater was identified in 71% of the postmenopausal patients and 32% of the premenopausal patients (P < 0.03). These findings show a high prevalence of significant cervical dysplasia among both premenopausal women over the age of 35 years, and postmenopausal women. Compared with younger women, the risk of CIN 2 or greater is at least the same if not higher among these two groups.

Estimating the Long-Term Clinical Impact of Cervical Cancer Vaccination in Taiwan

The high burden of human papillomavirus (HPV) infection and subsequent cervical cancer in the presence of screening in Taiwan suggests the need for further prevention strategies. Epidemiology and screening practices vary considerably between countries, and specific analyses are required to estimate the impact of HPV vaccination. This study adapted a computer-based health economic model to Taiwan to project the clinical impact of the introduction of a prophylactic vaccine against persistent HPV 16/18 infection on cervical disease. A Markov model based on the natural history of HPV and cervical cancer was developed to simulate transitions between health states (normal, HPV, cervical intraepithelial neoplasia [CIN] stages I to III, cervical cancer stages I to IV, and death) in the presence of screening. The model was calibrated to Taiwan epidemiological end points including age-specific HPV prevalence, prevalence of CIN lesions, and predicted cervical cancer incidence and mortality. Taiwanese screening and treatment practices were modeled, and published clinical trial data were used to estimate vaccine efficacy. With 100% vaccine coverage in a 13-year-old cohort of females, there is estimated to be a 71% reduction in cervical cancer cases and deaths due to all HPV types and substantial reductions in the prevalence of precancerous lesions and screening outcomes. Removing the risk of HPV infection of a large proportion of Taiwanese females, with a high underlying cervical cancer incidence rate, would be expected to have dramatic effects on the health care system and mortality in Taiwan.

RECENT STUDIES ON THE HPV VACCINE GARDASIL: ADDENDUM TO OCTOBER 2008 NOTE

This Note advocates that states require all females entering the sixth grade to be vaccinated with the HPV vaccine Gardasil, as a means of preventing cervical cancer deaths in the United States. States that do pass such a mandate would receive federal funding to help disperse the cost of the expensive three‐dose vaccine, especially to those females most in need. Subject to each individual state's mandate, parents would be allowed to opt their children out of such a mandate for either, religious, medical, and/or philosophical reasons.

HPV16/18 vaccination to prevent cervical cancer in The Netherlands: Model‐based cost‐effectiveness

We evaluated the cost-effectiveness of HPV16/18 vaccination for girls aged 12 years in The Netherlands in addition to cervical cancer screening. For this purpose, we developed a simulation model that describes the relation between each of the high-risk human papillomavirus (hrHPV) types and cervical disease, allowing the occurrence of multiple type-specific infections. Model parameters were derived from Dutch cohort studies, including a large population-based screening trial, and from the national cervical cancer registry. The model satisfactorily reproduced Dutch data on HPV infection and the presence of cervical lesions. For our base-case scenario in which 85% of the girls aged 12 years were vaccinated against types 16/18 (95% efficacy, lifelong protection), the model predicted a decrease of 60% in the number of cervical cancer cases and cervical cancer deaths indicating that substantial health benefits can be achieved. Health savings were robust against changes in the vaccine efficacy (varied from 85% to 98%) but savings showed a substantial reduction when the efficacy started waning 10 years after vaccination. The discounted costs per quality-adjusted life year (QALY) were euro 19,500/QALY (range euro 11,000 to euro 25,000/QALY) and lied near the cost-effectiveness threshold of euro 20,000/QALY used in The Netherlands. The simulations further showed that vaccination cannot replace screening because vaccination without screening was less effective than screening in preventing cancer in women over 40 years of age. In conclusion, our model results support the implementation of HPV16/18 vaccination in young women in addition to cervical cancer screening.

Cervical cancer incidence, mortality, and survival among Asian subgroups in California, 1990-2004

Aggregated cancer statistics for Asians mask important differences in cancer burden among Asian subgroups. The purpose of this study was to describe the relative patterns of cervical cancer incidence, mortality, and survival among Chinese, Filipino, Japanese, Korean, South Asian, and Vietnamese women in California, using data from the California Cancer Registry. All cervical cancer cases diagnosed among the 6 subgroups and non-Hispanic whites (NHW) from 1990 to 2004 were identified and used to calculate incidence and mortality rates and trends. The Kaplan-Meier method was used to calculate 5- and 10-year survival probabilities by subgroup, and Cox proportional hazards methodology was used to calculate survival differences adjusted for race and ethnicity, age, stage at diagnosis, socioeconomic status, and treatment factors. Vietnamese and Korean women experienced greater cervical cancer incidence and mortality than NHW women, whereas rates among Chinese, Japanese, and South Asians were comparable or lower. Five-year unadjusted survival probabilities were greatest for South Asians (86%) and Koreans (86%), followed by Vietnamese (82%), Chinese (79%), and Filipinos (79%), as compared with NHW (78%) and Japanese (72%). The adjusted risk of cervical cancer death was significantly lower for South Asians, Koreans, Vietnamese, and Filipinos than for NHW women, but not for Chinese and Japanese. Cervical cancer incidence rates vary substantially across the major Asian subgroups. Despite higher incidence and mortality rates compared with NHW women, Vietnamese, Koreans, and Filipinos have better survival outcomes. Further studies are needed to examine the factors behind these survival differences.

Abstract PL02-01: Global trends in cancer incidence: priorities for prevention

Abstract PL02-01: Global trends in cancer incidence: priorities for prevention

Human papillomavirus testing for primary cervical cancer screening

Cervical cancer is the second most common cancer in women worldwide and the seventh most common cause of cancer deaths in women in Europe. Today, we know how to prevent almost every case of this disease; organized cervical cancer screening based on the Papanicolaou or Pap smear has been proven to prevent 80% of cervical cancer deaths, while new technologies for the detection of the human papillomavirus (HPV) or the prevention of HPV infection offer the potential to make even more progress in the battle against this disease. Testing for carcinogenic or high-risk HPV types is gaining acceptance for the triage of women with borderline cytology and for follow-up after treatment of high-grade cervical lesions. Now, a number of large-scale randomized controlled trials have shown that HPV testing as a primary screening test can detect approximately 50% more high-grade lesions than the Pap test, albeit with a lower specificity if all HPV-positive women are followed up. However, alternative screening algorithms in which HPV-positive women are triaged with cytology have been shown to have equivalent specificity to the Pap test without compromising the increased sensitivity. Further advantages of HPV testing come from the fact that it is an objective and automatable test with a dichotomous result. These attributes can yield cost savings through reductions in staff numbers and simplification of quality control procedures while reducing turnaround times. In countries seeking to improve cervical cancer prevention, the implementation of HPV testing as the primary screening test with cytology for the triage of HPV-positive women is an option that should be fully evaluated. This review summarizes the recent advances in HPV testing in cervical cancer prevention.

CERVICAL CANCER PREVENTION: MANDATING THE HPV VACCINE AS A CONDITION OF SCHOOL ATTENDANCE

This Note advocates that states require all females entering the sixth grade to be vaccinated with the HPV vaccine Gardasil, as a means of preventing cervical cancer deaths in the United States. States that do pass such a mandate would receive federal funding to help disperse the cost of the expensive three‐dose vaccine, especially to those females most in need. Subject to each individual state's mandate, parents would be allowed to opt their children out of such a mandate for religious, medical, and/or philosophical reasons.

Mathematical Models of Cervical Cancer Prevention in the Asia Pacific Region

Using population-based and epidemiologic data for 25 countries in Asia (22 GAVI-Alliance eligible countries, Thailand, China and Japan), a model-based approach was used to estimate averted cervical cancer cases and deaths, disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (I$/DALY averted) for vaccination of young adolescent girls against human papillomavirus (HPV) types 16 and 18. Absolute reduction in lifetime cancer risk varied between countries, depending on incidence, proportion attributable to HPV-16 and -18, and population age-structure; for example, with 70% coverage, cancer reduction was 57% in Indonesia, whereas in Cambodia, it was 49%. Screening of women over age 30 three times per lifetime, after vaccinating them as pre-adolescents, is expected to provide an additional 20% to 30% mortality reduction. Of the 22 GAVI-Alliance eligible countries, India, Bangladesh, Vietnam and Indonesia account for 87% of the total DALYs averted. Assuming a cost per vaccinated girl of I$10 ($2 per dose), the cost per DALY averted is less than I$250 in 18 of 22 countries. Assuming a cost per vaccinated girl of I$25, the cost per DALY averted is I$1,360 in China compared with I$250 in Thailand, reflecting the greater number of girls that need to be vaccinated to prevent a death from cervical cancer in China. Vaccine price has an even greater effect on predicted affordability. For the 22 GAVI Alliance-eligible countries, vaccinating 5 consecutive birth cohorts at 70% coverage would cost over US $500 million versus almost US $1.3 billion at per dose costs of $2 and $5, respectively. Including China and Thailand would add US $251 million to US $1.4 billion at per dose prices of $2 and $12.25, respectively. In the countries we assessed, vaccination of young adolescent girls against HPV-16 and -18 could be very cost-effective if the cost per vaccinated girl is less than I$10–I$25; for it to be affordable, however, even with financing assistance, vaccine prices may need to be even lower.

Mathematical Models of Cervical Cancer Prevention in Latin America and the Caribbean

Using population and epidemiologic data for 33 countries in Latin America and the Caribbean (LAC), a model-based approach estimated averted cervical cancer cases and deaths, disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (I$/DALY averted) for human papillomavirus (HPV) vaccination of young adolescent girls. Absolute reduction in lifetime cancer risk varied between countries, depending on incidence, proportion attributable to HPV-16 and 18, and population age-structure; for example, with 70% coverage, cancer reduction ranged from 40% in Mexico to more than 50% in Argentina. Screening of women over age 30 three times per lifetime, after vaccinating them as pre-adolescents, is expected to provide a relative increase of 25% to 30% in mortality reduction. Countries with the highest risk of cancer (age-standardized rate > 33.6) accounted for only 34% of deaths averted with vaccination, highlighting why a regional universal vaccination approach will be most effective in reducing the overall global burden. At I$25 per vaccinated girl ($5 per dose), for all 33 countries, the cost per DALY averted is less than I$400; at I$10 ($2 per dose) the vaccine is cost saving in 26 out of 33 countries. For all countries, ratios become less attractive (i.e., increase) as the cost of the vaccine increases. For example, at current vaccine prices ($120 per dose), the cost per DALY averted is I$7,300 in Mexico, I$3,700 in Nicaragua, and I$6,300 in Costa Rica. Vaccine price has an even greater effect on predicted affordability. For the 33 countries, vaccinating 5 consecutive birth cohorts at 70% coverage would cost $360 million at $5.00 per dose, $811 million at $12.25 per dose, and $1.26 billion at $19.50 per dose. In the LAC region, if effective delivery mechanisms can achieve high coverage rates in young adolescent girls, vaccination against HPV-16 and 18 will provide similar health value for resources invested as other new vaccines such as rotavirus. If the cost per vaccinated girl is less than I$25 HPV-16/18 vaccination would be very cost-effective in all 33 countries; for it to be affordable, costs may need to be lower.

Long-term clinical impact of introducing a human papillomavirus 16/18 AS04 adjuvant cervical cancer vaccine in Spain

Human papillomavirus (HPV) epidemiology and screening practices vary considerably between countries and specific analyses are required to estimate the impact of HPV vaccination. This study aimed to predict the clinical benefits of introducing a bivalent HPV16/18 vaccine in Spain, where the cervical cancer (CC) incidence is 10.3 per 100 000. A Markov model based upon the natural history of HPV and CC was developed to simulate transitions between health states, in the presence of specific screening programmes. Published data were used to reflect the Spanish situation in terms of epidemiological characteristics, screening and treatment practices. Calibration consisted of varying disease progression rates within established ranges until model predictions matched observed epidemiological data. The clinical impact of vaccinating a cohort of 12-year-old girls against HPV was assessed over their lifetime using the calibrated model. Vaccination of all 12-year-old girls would result in a reduction of 75% (from 0.32% to 0.08%) in the prevalence of high-grade precancerous lesions due to oncogenic HPV, and a 79% reduction in both CC cases (from 1745 to 365) and CC deaths (from 417 to 86). Assuming a vaccine coverage of 80%, the number of CC cases and deaths would decrease by 63%. Vaccination could also substantially reduce the number of screening tests and treatments required for cervical dysplasia. Our model was successfully adapted to the Spanish epidemiological environment, screening and treatment practices and predicted a substantial long-term benefit of HPV vaccination despite a low HPV prevalence in Spain.

A sexual health prevention priority

Wittet and Tsu are right to point to the link between cervical cancer deaths and achieving the MDGs and the inequity in the burden of cervical cancer between developed and developing countries. Any programme that reduces cervical cancer incidence and mortality rates in low-income and lower middle-income countries is clearly to be welcomed. Addressing women’s welfare, family education and thus poverty through screening, treatment and prevention will play an important role in tackling inequalities, although access to screening and vaccination is likely to be inequitable if programmes are not provided in a systematic and comprehensive way. We would argue, though, that cervical cancer screening and HPV vaccination should be seen as integral parts of, rather than separate from or instead of, a wider sexual health promotion programme. Cervical cancer prevention can be viewed in a similar way to any other sexually transmitted infection. Screening women for cervical cancer is clearly important but a comprehensive and universal screening programme requires substantial resources and infrastructure and so the opportunity costs of such a programme need to be carefully considered. All cancer screening programmes result in unnecessary intervention or lack of intervention due to the sensitivity and specificity of tests that can be costly in terms of public spending but also in personal anxiety and distress.1–3 As Wittet and Tsu report, however, new “see and treat” programmes will make an important contribution to cervical cancer treatment. The recently developed HPV vaccine offers some hope in reducing the levels of cervical cancer but concerns have been expressed about its efficacy and the usefulness of vaccination programmes – particularly with regard to long-term effects and that it only protects against 4 out of the 200 HPV viruses. Key questions need to be asked about how vaccination is offered and to whom. It is only effective in women if given before commencing (heterosexual) sexual activity and herd immunity will only be achieved if both young men and women are vaccinated. Vaccination programme effectiveness would also need to be based on known rates of HPV infection as cervical cancer can also be caused by strains other than those for which the vaccine provides protection. Studies in the United States of America suggest that the incidence for types 16 and 18 is significantly lower than previously thought, that infection rates vary by age and most HPV infections are asymptomatic.4–7 This is an important point when considering the primary prevention of cervical cancer and HPV infection. Cervical cancer is usually a sexually transmitted disease, yet as many as two-thirds of women who are infected with the HPV virus will not develop cervical cancer. Primary prevention strategies providing factual information regarding transmission of sexually transmitted infection (STI) and the teaching of safer sex negotiation skills are potentially highly effective at a relatively low cost.8 Condom use has been shown to help prevent the transmission of the HPV virus as well as other STIs. However, in many circumstances it is not always possible for women to negotiate the use of the condom, especially within marriage. Of particular interest, therefore, are current studies being undertaken in Nairobi and Zimbabwe to examine the use of the diaphragm as a tool to prevent the transmission of not only HPV, but also HIV and other STIs.9,10 The advantage of the diaphragm for women is that her partner is not necessarily aware that she is using the device, which can be cleaned and reused. While of obvious benefit and importance, cervical cancer screening programmes and HPV vaccination are not in themselves totally effective strategies. Screening may detect early (or more advanced) lesions but this is not without problems. Likewise, a population vaccination programme for HPV also raises questions that have, so far, not been answered satisfactorily. Primary prevention through education and promotion of safe sexual practices must, therefore, remain a key plank of any programme aimed at reducing cervical cancer deaths in the long term and substantially contributing to the MDGs. ■

Health and economic outcomes of HPV 16,18 vaccination in 72 GAVI-eligible countries

The risk of dying from cervical cancer is disproportionately borne by women in developing countries. Two new vaccines are highly effective in preventing HPV 16,18 infection, responsible for approximately 70% of cervical cancer, in girls not previously infected. The GAVI Alliance (GAVI) provides technical assistance and financial support for immunization in the world's poorest countries. Using population-based and epidemiologic data for 72 GAVI-eligible countries we estimate averted cervical cancer cases and deaths, disability-adjusted years of life (DALYs) averted and incremental cost-effectiveness ratios (I$/DALY averted) associated with HPV 16,18 vaccination of young adolescent girls. In addition to vaccine coverage and efficacy, relative and absolute cancer reduction depended on underlying incidence, proportion attributable to HPV types 16 and 18, population age-structure and competing mortality. With 70% coverage, mean reduction in the lifetime risk of cancer is below 40% in some countries (e.g., Nigeria, Ghana) and above 50% in others (e.g., India, Uganda, Kenya). At I$10 per vaccinated girl (∼$2.00 per dose assuming three doses, plus wastage, administration, program support) vaccination was cost-effective in all countries using a per capita GDP threshold; for 49 of 72 countries, the cost per DALY averted was less than I$100 and for 59 countries, it was less than I$200. Taking into account country-specific assumptions (per capita GNI, DPT3 coverage, percentage of girls who are enrolled in fifth grade) for the year of introduction, percent coverage achieved in the first year, and years to maximum coverage, a 10-year modeled scenario prevented the future deaths of ∼2 million women vaccinated as adolescents. Despite favorable cost-effectiveness, assessment of financial costs raised concerns about affordability; as the cost per vaccinated girl was increased from I$10 to I$25 (approximately $2 to $5 per dose), the financial costs for the 10-year scenario increased from >US$ 900 million to US$ 2.25 billion. Provided high coverage of young adolescent girls is feasible, and vaccine costs are lowered, HPV 16,18 vaccination could be very cost-effective even in the poorest countries, and provide comparable value for resources to other new vaccines such as rotavirus.

Vaccination against human papillomavirus

The debate surrounding the HPV vaccine[1][1] might be characterized by 2 slogans: “Just do it” versus “What's the hurry?” The HPV vaccination program's supporters see any potential reductions in cervical cancer deaths as sufficient justification for starting the program immediately. Others