Human papillomavirus (HPV) infection in Southern Africa: prevalence,immunity, and vaccine prospects

Human papillomavirus (HPV) associated cancers are more prevalent in developing countries compared to developed countries. The major cancer caused by HPV is cervical cancer. The humoral immune response to HPV can be a marker of past infection but may also reflect persistent infection and cervical disease. IgA antibodies to HPV in oral fluid were also found to be markers of cervical disease. Cell mediated immunity is important in clearing HPV infection and for regression of the associated lesions: this means that women infected with HIV have a high prevalence of co-infection with HPV. Good cervical screening programmes can control HPV associated cervical neoplasia. However, in countries such as South Africa, where these programmes are inadequate, there is a need for an HPV vaccine. The development of HPV vaccines is reviewed. There is a call for an inexpensive vaccine that will be accessible to the women that do not have access to adequate screening programmes and are therefore at the greatest risk of cervical cancer.     

HPV technologies advancing public health: discussion of recent evidence

Effective primary and secondary cancer prevention programmes are key to improve public health. Cervical cancer is preventable if high quality screening programmes, diagnosis and treatment are offered to female populations at high coverage. Nevertheless, it continues to be a public health problem, and screening programmes need improvements. Human papillomavirus (HPV) has been firmely established as the necessary cause of virtually all cervical cancer cases. To date we count two clinically validated and approved HPV technologies, available to prevent cervical cancer, and other diseases caused by these carcinogenic viruses: Prophylactic vaccines for primary prevention, and HPV DNA tests for secondary prevention, to detect life threatening infections by carcinogenic HPV types, allowing timely diagnosis and clinical management of precancerous lesions. The new technologies will help improve the health of the public if made widely accessible. Similar to vaccination programmes, systematic and well organized cervical screening programmes, with high quality validated HPV tests, can save more lives than ever and improve women's health, in an effective manner.     

The burden of cervical cancer in south-east Europe at the beginning of the 21st century

The situation of cervical cancer prevention in South-East Europe is hardly documented, in spite of the fact that it encloses the most affected countries of Europe. We estimated the number of cases of cervical cancer, the number of deaths from this malignancy and the corresponding rates for 11 countries located in South-East Europe, in the period 2002-2004. Each year, approximately 9,000 women develop cervical cancer and about 4,600 die from the disease in this subcontinent. The most affected country is Romania with almost 3,500 cases and more than 2,000 deaths per year High world-age standardised mortality rates (> 7.5 [expressed per 100,000 women-years]) are observed in 7 countries: FYROM (7.6), Moldova (7.8), Bulgaria (8.0), Bosnia & Herzegovina (8.0), Albania (9.8), Serbia & Montenegro (10.1) and Romania (13.0). A matter of concern is the increasing mortality rate, in younger women, in the countries with the highest burden of cervical cancer. Thus, appropriate cervical cancer prevention programmes should be set up without delay in this part of Europe.     

The invasive cervical cancer review: psychological issues surrounding disclosure

An audit of the screening history of all new cervical cancer cases has been a requirement since April 2007. While NHS cervical screening programmes (NHSCSP) guidance requires that women diagnosed with cervical cancer are offered the findings of the audit, as yet there has been no research to investigate the psychological impact that meeting to discuss the findings might have on patients. This is in spite of the fact that cytological under‐call may play a role in as many as 20% of cervical cancer cases. This review draws on the literature concerning breaking bad news, discussing cancer and disclosing medical errors, in order to gain insight into both the negative and positive consequences that may accompany a cervical screening review meeting. We conclude that while patients are likely to experience some distress at disclosure, there are also likely to be positive aspects, such as greater trust and improved perception of care.     

Predicting mortality from cervical cancer after negative smear test results.

OBJECTIVE--To assess the relative protection against death from cervical cancer after two or more negative smear test results and compare it with the protection against invasive cancer estimated by an International Agency for Research on Cancer (IARC) working group in an analysis of data from 10 large screening programmes. DESIGN--Comparison of risk of death from cervical cancer after two or more negative smear results with the risk in unscreened women by using a model constructed with data from the British Columbia screening programme. MAIN OUTCOME MEASURES--Mortality from and incidence of invasive cancer. RESULTS--In women with two negative smear results estimates of protection against cervical cancer were about 50% higher when lethal invasive cancer was used as the criterion rather than all invasive cancer. This difference was due to these women being more likely to attend for further tests at which invasive cancer could be detected: screen detected cancer has a better prognosis than clinically diagnosed cancer. Screening intervals could be longer than three years: screening women aged 35-64 every five years was predicted to result in a 90% reduction in mortality from cervical cancer. CONCLUSION--Because protection from mortality is higher than protection from disease and because of the high costs and negative side effects of frequent screening, screening intervals should be longer than three years.     

Screening for squamous cervical cancer: duration of low risk after negative results of cervical cytology and its implication for screening policies. IARC Working Group on evaluation of cervical cancer screening programmes.

A collaborative study of screening programmes in eight countries was performed to estimate the risks of cervical cancer associated with different screening policies. Most of the data came from centrally organised screening programmes. Relative protection was higher in women who had had two or more negative results of screening tests than in those who had had only one negative smear, particularly in the first five years after the last test. There was little difference in the protection afforded by screening every year compared with every three years, but screening only once every five or 10 years offered appreciably less protection. The age of the women did not affect the sensitivity of the test or the sojourn time of the disease (the length of the detectable preclinical phase during which abnormal cytology could be picked up if a smear were taken); invasive cancer in women under 25 was rare. Centrally organised screening programmes were more effective than uncoordinated screening. Screening programmes should be aimed principally at women aged 35-60 but should start some years before the age of 35, and the intervals between screening should be three years or less.     

人乳头瘤病毒感染与宫颈癌的研究进展

人乳头瘤病毒(Human Papillomavirus HPV)感染是导致性传播疾病的常见原因,上世纪八十年代初,首次报道生殖器HPV感染与宫颈癌之间的联系,认为HPV感染是95%以上宫颈癌变的高危因素。随着分子生物学技术的发展,对HPV致癌机制的研究不断深入,取得大量有价值的成果,现就HPV的致癌途径与协同因素探讨宫颈癌的发病机制以及对HPV检测方法等方面的研究进行综述。     

The early detection of cervical cancer. The current and changing landscape of cervical disease detection

Cervical cancer prevention has undergone dramatic changes over the past decade. With the introduction of human papillomavirus (HPV) vaccination, some countries have seen a dramatic decline in HPV‐mediated cervical disease. However, widespread implementation has been limited by economic considerations and the varying healthcare priorities of different countries, as well as by vaccine availability and, in some instances, vaccine hesitancy amongst the population/government. In this environment, it is clear that cervical screening will retain a critical role in the prevention of cervical cancer and will in due course need to adapt to the changing incidence of HPV‐associated neoplasia. Cervical screening has, for many years, been performed using Papanicolaou staining of cytology samples. As our understanding of the role of HPV in cervical cancer progression has advanced, and with the availability of sensitive detection systems, cervical screening now incorporates HPV testing. Although such tests improve disease detection, they are not specific, and cannot discriminate high‐grade from low‐grade disease. This has necessitated the development of effective triage approaches to stratify HPV‐positive women according to their risk of cancer progression. Although cytology triage remains the mainstay of screening, novel strategies under evaluation include DNA methylation, biomarker detection and the incorporation of artificial intelligence systems to detect cervical abnormalities. These tests, which can be partially anchored in a molecular understanding of HPV pathogenesis, will enhance the sensitivity of disease detection and improve patient outcomes. This review will provide insight on these innovative methodologies while explaining their scientific basis drawing from our understanding of HPV tumour biology.     

Cervical screening in England and Wales: its effect has been underestimated

Opinions about cervical screening in the UK tend to follow one of two negative lines of thought. The first is that cervical cancer is a rare disease, and too much time and effort are spent on screening. The second is that it has been relatively ineffective, since incidence of invasive carcinoma did not fall until the NHS Cervical Screening Programme (NHSCSP) was introduced in 1988, although it fell by 40% since then. This paper presents publicly available data to demonstrate that neither of these views is true. Registrations of invasive carcinoma of the uterine cervix and carcinoma in situ in England and Wales between 1971 and 1996 show that a substantially increased risk of disease in women born since 1940 has been reversed, almost certainly by greatly improved screening. Cervical carcinoma is now a rare disease because most cases are prevented before they become invasive, mostly by screening young women, aged 20-40, before the decade of life when symptomatic cervical carcinoma most frequently presents.     

Cancer prevention in primary care. Screening for cervical cancer.

Cervical screening has been shown to be effective in several countries, although not by means of randomised controlled trials. A screening programme has been in operation in the United Kingdom since 1964, but it has, in the past, been beset with problems of organisation, accountability, and commitment. The introduction in 1988 of a systematic call and recall introduction in 1988 of a systematic call and recall system and the setting up of an NHS cervical screening programme national coordinating network has brought a greater sense of coherence. Coverage of the target population in England between 1989-90 and 1992-3 increased from 61% to 83%, and there is a strong indication that cervical screening is now beginning to reach those most at risk--namely, older women from lower social classes. Primary care is central to the overall success of the cervical screening programme. General practitioners are in a unique position to invite women for a smear test, to take smears, to ensure that abnormal smear test results are followed up, and to check on reasons for non-attendance. Numerous studies have looked at the involvement of general practice in cervical screening, identifying many ways in which the programme can be improved. Many practices are now running well organised and effective programmes.     

Cervical screening in the UK and laboratory quality control in the context of the 2007 European guidelines

The first part of this article will provide an overview of cervical cancer screening in the UK during the years before, during and after the introduction of a highly successful centrally organised cervical screening programme in 1988: since then the incidence of invasive cervical cancer has fallen by more than 40%. Screening was introduced in a background of opportunistic screening with poor quality control during a period of time when risk of disease was increasing, which will be demonstrated by national registrations of carcinoma in situ as well as invasive cancer. The programme is still facing new challenges and has recently recorded falling screening coverage in younger women, the causes of which have yet to be established. Liquid-based cytology is in the process of being rolled out nationally but high-risk human papillomavirus testing has yet to be introduced into the National Health Service (NHS) programme. Lessons from our experience may be relevant to countries introducing and maintaining organised programmes elsewhere under similar circumstances. The second part of the article will consider laboratory quality control as practiced in the UK and as recommended in the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. These evidence-based guidelines provide recommendations for organising and monitoring quality control as well as for introducing new technology and standardising terminology, which are equally relevant for new and existing programmes. Invasive cancer audit may highlight areas where procedures could be improved in any programme but also can also demonstrate the effectiveness of screening.     

Present challenges in cervical cancer prevention: Answers from cost-effectiveness analyses

Simulation models are commonly used to address important health policy issues that cannot be explored through experimental studies. These models are especially useful to determine a set of strategies that result in a good value for money (cost-effectiveness). Several mathematical models simulating the natural history of HPV and related diseases, especially cervical cancer, have been developed to calculate a relative effectiveness and cost-effectiveness of HPV vaccination and cervical cancer screening interventions. Virtually all cost-effectiveness analyses identify HPV vaccination programmes for preadolescent girls to be cost-effective, even for relatively low vaccination coverage rates. Routine vaccination of preadolescent girls is the primary target population for HPV vaccination as it shows to provide the greatest health impact. Cost-effectiveness analyses assessing other vaccine target groups are less conclusive. Adding additional age-cohorts would accelerate health benefits in some years, although cost-effectiveness becomes less favourable as age at vaccination increases. Including men in HPV vaccination programmes may be a less efficient strategy if done at the expense of female vaccination coverage for reducing the burden of HPV in the population. However, as the HPV vaccine price decreases, the cost-effectiveness of universal vaccination improves, becoming equally as efficient as female-only vaccination. Vaccine price is a decisive factor in the cost-effectiveness analyses. The lower the price, the greater the likelihood that vaccination groups other than the primary target would be considered cost-effective.     

An unanticipated source of hope: stigma and cervical cancer in Brazil

In this article, I argue that although cervical cancer is an often stigmatized condition in Brazil, women with cervical cancer in Recife, Brazil, did not simply endure the stigma, they also perpetuated it. I draw on narrative theory and 18 months of ethnographic research in Recife to argue that rather than resisting the stigma associated with their disease, women in Recife used stigma to construct illness narratives that affirmed that they were still held to the same norms and values as the nonill. In turn, those narratives, and the healing narratives constructed along with them, provided women with hope for a future free from cervical cancer and free from the "imperfections" associated with that disease. Thus, women with cervical cancer used stigmatizing narratives both as links back to the "normal" world they inhabited before they became ill, and as bridges forward to the future they hoped to attain.     

Trends in incidence of,and mortality from,cervical lesions in Ireland: Baseline data for future evaluation of the national cervical screening programme

AimTo investigate incidence and mortality trends for cervical lesions in Ireland in the period 1994–2008.MethodsWe used data from the National Cancer Registry, Ireland and national death registration data to calculate age-standardised rates for the periods of interest. We used standardised rate ratios to test whether incidence was associated with socio-demographic variables and used Joinpoint to examine trends by morphology grouping.ResultsIncidence of cervical cancer and cervical intraepithelial neoplasia (CIN3) rose over the period 1994–2008. The annual percentage change for cervical cancer was 1.8% and that for CIN3 was 3.8%. Women resident in the most deprived areas had invasive cervical cancer incidence almost twice as high as those resident in the least deprived areas (standardised rate ratio (SRR) = 1.8). Comparing incidence in Ireland to England and Wales, Northern Ireland and Scotland in the three years 2005–2007, the SRRs (other areas vs. Ireland) were 0.70, 0.88 and 0.84 respectively. Cervical cancer rates have fallen in these countries in the same period that there is a rise demonstrated in Ireland.ConclusionIncidence rates of cervical cancer rose in Ireland steadily, albeit modestly, during 1994–2008, most likely due to long-term changes in patterns of sexual behaviour and contraceptive use. A more pronounced rise in CIN3 rates point to considerable levels of opportunistic screening during this period. Mortality rates have changed little over the past four decades, in contrast to trends in countries with well-organised screening programmes.     

HPV testing for cervical cancer screening in Croatia

Opportunistic screening based on the Pap smear has been undertaken in Croatia since 1953. However, cervical cancer remains an important health problem in Croatia when compared to European countries with organised screening programmes. In Croatia, in addition to screening based on well established cytology, Human papillomavirus (HPV) testing is widely used as secondary test as a triage to borderline cytology and as a follow-up after treatment of severe cervical lesions. Many different approaches for HPV testing arose in Croatia over the last decade depending on the needs of each medical institution involved. Presently, there is an urgent need for better networking between the laboratories, the implementation of quality assessment and the adaptation of a uniform system of referring to and reporting of HPV testing. In conclusion, the best possible organisation for HPV testing would be essential for implementation of HPV testing as primary screening test in Croatia, an thus ultimately and hopefully, the more successful cervical cancer control.     

Cervical cancer vaccines: emerging concepts and developments

Certain human cancers are linked to infection by oncogenic viruses that are able to cause transformation of the normal host cell into a cancerous cell. Human papillomavirus (HPV) DNA and expression of viral transforming proteins are found in virtually all cervical cancer cells, indicating an important role of this virus in the pathogenesis of the disease. Evidence exists that the immune response to cancer cells can play a major role in determining the outcome of disease. The fact that HPV is a necessary cause for cervical cancer provides a clear opportunity to develop a therapeutic vaccine against the virus to treat patients with cervical cancer at its early and late stages. Development of a prophylactic vaccine for HPV would also reduce the incidence of cervical neoplasias by preventing virus infection. Various candidate HPV vaccines are being developed and tested in animal models and/or in human clinical trials. These HPV vaccines, both preventive and therapeutic, are the subjects of this review.     

Strategies against human papillomavirus infection and cervical cancer

Papillomaviruses infect a wide variety of animals, including humans. The human papillomavirus (HPV), in particular, is one of the most common causes of sexually transmitted disease. More than 200 types of HPV have been identified by DNA sequence data, and 85 HPV genotypes have been well characterized to date. HPV can infect the basal epithelial cells of the skin or inner tissue linings, and are, accordingly, categorized as either cutaneous or mucosal type. HPV is associated with a panoply of clinical conditions, ranging from innocuous lesions to cervical cancer. In the early 1980s, studies first reported a link between cervical cancer and genital HPV infection. Genital HPV infections are now recognized to be a major risk factor in at least 95% of cervical cancers. 30 different HPV genotypes have been identified as causative of sexually transmitted diseases, most of which induce lesions in the cervix, vagina, vulva, penis, and anus, as the result of sexual contact. There is also direct evidence demonstrating that at least four of these genotypes are prerequisite factors in cervical cancer. The main aim of this review was to evaluate the current literature regarding the pathovirology, diagnostics, vaccines, therapy, risk groups, and further therapeutic directions for HPV infections. In addition, we reviewed the current status of HPV infections in South Korean women, as evidenced by our data.     

Interlaboratory reproducibility of atypical squamous cells of undetermined significance report: a national survey

The study was aimed at assessing interlaboratory reproducibility in the reporting of cervical smears in the atypical squamous cells of undetermined significance (ASCUS) category. A set of 50 selected slides circulated among 89 laboratories, currently involved in population-based screening programmes for cervical cancer, which provided a diagnostic report according to four main reporting categories based on the 1991 Bethesda system. Interlaboratory agreement was determined according to kappa (K) statistics: overall and weighted K values were determined for each laboratory and for single reporting categories. The results showed a very low reproducibility for the ASCUS category. This finding supports the Bethesda system 1991 recommendation to limit the use of this reporting category and suggests that the clinical response to ASCUS reports should be decided locally, based on the observed positive predictive value for cervical intraepithelial neoplasia 2 or more severe lesions.     

Changing character of cervical cancer in young women.

To examine the hypothesis that the pattern of cervical cancer is changing data on women presenting with the disease over 34 years were studied retrospectively. During 1953-86, 2628 women with cervical cancer were referred to a large tertiary referral hospital in Sydney; 418 were aged 35 or less. During the period of review the proportion of young women with the disease increased from under 9% in the 1950s and 1960s to about 25% in the 1970s and 1980s; a similar but less pronounced trend was apparent for the whole of New South Wales in the 1970s and 1980s. The prevalence of less common morphological types of cervical cancer increased throughout the period, particularly in the young. Pelvic lymph node metastases were identified in younger patients with stage Ib and IIa tumours more commonly in the later years of the study, suggesting that the disease was becoming more severe. Overall rates of recurrence improved over time, but an apparent increase in early recurrences was observed in young patients with Ib and IIa tumours and without nodal disease. The results suggest that the clinical and pathological behaviour of cervical cancer changed over the period of review.