Gynaecological cancers in Umbria (Italy): trends of incidence, mortality and survival, 1978-1998

OBJECTIVE: For the period 1978-1998 incidence, mortality and survival from gynaecological cancers in the Umbria region (Central Italy) were examined. STUDY DESIGN: Mortality data were derived from the National Institute of Statistics while incidence and survival data were provided by an ad hoc survey carried out over the period 1978-1982 and by the Umbrian Population-Based Cancer Registry operating since 1994. Age-standardised mortality and incidence rates were calculated. Survival was assessed using the Estève method. Mortality trends were analysed by joinpoint regression model. RESULTS: In the Umbria Region, over the period 1978-1998, the incidence rate of cervical cancer decreased, while those for endometrial and ovarian cancers rose. By contrast, the mortality rates from ovarian and endometrial cancers decreased, while that for cervical cancer rose slightly. Comparing relative survival rates, at 5 years an increase in survival was reported for ovarian cancer, cervical cancer remained constant and endometrial cancer slightly decreased; at 1 year only the ovarian cancer survival improved. Nevertheless, age-standardised survival rates showed that survival improved in all examined sites. CONCLUSIONS: The improvement in diagnosis and in data coding could have determined an increase in endometrial and ovarian cancer incidence, while the dramatic decrease in cervical cancer incidence is probably due to the effectiveness of cervical screening.     

Knowledge of cervical cancer and screening among women in east-central England

Abstract.   Philips Z, Avis M, Whynes DK. Knowledge of cervical cancer and screening among women in east-central England. Int J Gynecol Cancer 2005; 15: 639–645.
This study assesses the extent and accuracy of women's knowledge of cervical cancer, risk factors, and the efficacy of the national screening program. Data were obtained from a questionnaire survey of randomly selected women eligible for screening, drawn from a population in east-central England. The majority of women in the sample overestimated the current incidence of cervical cancer, both absolutely and relative to other cancers. Perceiving incidence to be high was associated with reporting worries about the disease. With respect to the screening process, 78.3% believe that the smear abnormality rate is higher than it actually is, and only 7.6% correctly appreciate that the abnormality rate is highest at younger ages. With respect to performance, 16.3% believed the smear test to be completely accurate, and more than half overestimated the likely number of cancer cases prevented by screening. While certain cervical cancer risk factors were correctly assigned by the majority of women, undue emphasis was placed on genetic influence, while the risks posed by human papillomavirus infection were unfamiliar to almost half of the sample. We conclude that women typically possess only a partial picture of risk factors and overestimate both the incidence of cervical cancer and the efficacy of screening.     

宫颈癌HPV预防性疫苗的研究进展

人乳头瘤病毒（HPV）感染是常见的性传播疾病之一。高危人乳头瘤病毒（hrHPV）持续感染是宫颈癌前病变及宫颈癌的主要危险因素。HPV16和HPV18型导致全球大约70%的宫颈癌。宫颈癌普查可减少宫颈癌发生的危险,但不能阻止HPV的感染。很多报道表明,有效的HPV疫苗可以减少HPV相关的宫颈癌、生殖道疣状物的发病率和死亡率。因此,为了有效预防这类疾病,全世界开展了HPV预防性疫苗的研究。目前临床应用的HPV疫苗有HPV 2价疫苗、4价疫苗及9价疫苗,它们可以有效预防相应HPV类型的感染,从而大量减少与此相关的宫颈病变及宫颈癌的发病率和死亡率。本文就HPV、宫颈癌及这3类HPV疫苗的免疫原性、接种剂量的数量和临床应用进行综述。     

Human papillomavirus,cervical screening and ethical considerations

Human papillomavirus (HPV) is an extremely prevalent virus linked to multiple cancers, but most notably cervical cancer. The cervical screening programme in the UK has developed significantly since it was first introduced in 1964. This, together with the introduction of HPV vaccination, has made a huge difference to the early diagnosis and mortality for cervical cancer patients. Uptake of screening is paramount and this article addresses the barriers to this, and how these might be overcome. Other ethical issues around the topic of HPV, vaccination and screening include discrimination around sexual behaviour and orientation, education, vaccination availability and vertical transmission. This is an area of medicine that continues to develop and evolve as we understand more about HPV and how to tackle it.     

Invasive carcinoma of the cervix

Cervical cancer remains the second most common cancer worldwide despite becoming a relatively rare disease in developed countries. It is associated with sexual activity with human papilloma virus being the likely causative agent. Cervical screening has proven to be successful in reducing incidence and mortality from cervical cancer. Primary treatment is based on FIGO classification which is a clinical staging. Traditional radical surgery and radiotherapy have undergone recent changes as a result of minimal access surgery and recent trials on the benefit of chemoradiation.The NHS executive document ‘Improving Outcomes in Gynaecological Cancer’ has recommended that all women with cervical cancer more advanced that FIGO stage Ia and all adenocarcinomas should be referred to the specialist gynaecological oncology team at the cancer centres.The role of vaccines against human papilloma virus is currently being evaluated and hopefully will prevent the development of invasive cervical cancer worldwide.     

Screening history in women with cervical cancer in a Danish population-based screening program

Objective.

The aim of this study was to explore the screening histories of all cervical cancers in a Danish screening population. The intention was to decide suboptimal sides of the screening program and to evaluate the significance of routine screening in the development of cervical cancer.

Methods.

The study describes the results of a quality control audit, performed on all new cervical cancer cases diagnosed in the years 2008-2009 at two major Danish screening-centers. All relevant cytological and histological cervical samples were reviewed.

Results.

202.534 cytological samples were evaluated in the study period, while 112 women were diagnosed with cervical cancer. The histological diagnoses comprised: 62 (55.4%) squamous cell carcinomas, 20 (17.9%) microinvasive squamous cell carcinomas, 25 (22.3%) adenocarcinomas and 5 cancers of different histology. The mean age of study subjects was 46.6 years. 51 (45.5%) women had deficient screening histories, while 45 (40.2%) women had followed the screening recommendations and had normal cervical samples in review. 11 (9.8%) women were diagnosed with false negative cytology, 2 women had false negative histological tests, while pathological review was not feasible for 3 subjects.

Conclusions.

More than 45% of the cervical cancer cases in our study were due to deficient cervical screening, stressing the importance of increasing the screening-uptake and coverage. 40% interval cancers emphasize the relevance of further cervical testing of women with relevant symptoms, despite of prior normal cervical samples. Finally, 9.8% false negative cytological samples are consistent with previous reports, but still a part of the screening program that should be improved.     

Cervical cancer in Canada: Changing patterns in incidence and mortality

Abstract. Liu S, Semenciw R, Probert A, Mao Y. Cervical cancer in Canada: Changing patterns in incidence and mortality.
Data on incidence of cervical cancer by histologic subtype and mortality for the Canadian provinces of Ontario, Saskatchewan, and British Columbia were used to examine time trends by age, calender period, and birth cohort. Age-adjusted incidence rate of squamous cell carcinoma of the cervix decreased from 11.1 per 100,000 women in 1970–72 to 5.3 in 1994–96, while the rate for cervical adenocarcinoma increased from 1.1 per 100,000 women to 1.5 over the same period. Age-adjusted mortality rate declined from 7.9 per 100,000 women in 1953–55 to 1.9 in 1995–97. The patterns in age-specific mortality rates in 1953–72 were different from those in 1973–97; younger women experienced larger reductions in mortality during the earlier period while older women benefited to a greater extent during the latter period. Age-period-cohort modeling showed that cohort effects were responsible for the decreasing trends in incidence of squamous cell carcinoma of the cervix and increasing trends in adenocarcinoma, and both period and cohort effects account for the observed trends in mortality. The results suggest that Pap smear screening has played a significant role in the reduction in squamous cell cervical carcinoma. The causes for the increase in cervical adenocarcinoma are unclear.     

Cytology and DNA HPV-testing in the era of HPV-vaccine

Human papillomavirus (HPV) persistent infection is the main factor leading to the cervical cancer carcinogenesis. Wide-spread public vaccination against HPV as primary prevention is expected to reduce cervical cancer incidence and mortality rates. It is essential to bear in mind that screening for precancerous lesions cannot be discontinued because vaccination will not protect the patients against HPV types which have not been included in the first and second generation of vaccines.     

Time trends in the incidence of cervical and other genital squamous cell carcinomas and adenocarcinomas in Sweden, 1958-1996.

OBJECTIVES: We wanted to examine reasons for the different incidence trends for cervical squamous cell carcinoma (SCC, declining) and adenocarcinoma (increasing). METHODS: The Swedish Family-Cancer Database on 9.6 million individuals was used to derive incidence trends between 1958 and 1996. Cervical cancers were compared to vaginal and vulvar cancers. RESULTS: A total of 15405 invasive cervical SCCs and 1920 adenocarcinomas were identified. The incidence of SCCs decreased and that of adenocarcinoma increased during the study period, with similar trends among the in situ forms. The incidence of in situ vaginal and vulvar SCC increase 22-fold, whereas, invasive SCC and adenocarcinoma remained unchanged. The age-incidence curves for adenocarcinoma resembled those for SCC before screening, suggesting similar clinical course. CONCLUSIONS: The data suggest that the increase in the incidence of adenocarcinoma is related to an increasing prevalence of human papilloma virus (HPV) infection in female genitals, perhaps in addition to other factors. The increase is not seen in SCC because of effective screening.     

Social inequality in Pap smear coverage: identifying under-users of cervical cancer screening in Argentina

In Argentina, the unequal distribution of the burden of cervical cancer is striking: the mortality rate of the province of Jujuy (15/100,000) is almost four times higher than that of the city of Buenos Aires (4/100,000). We aimed to establish the socio-demographic profile of women who were under-users of Pap smear screening, based on an analysis of a representative sample of Argentinean women from the First National Survey on Risk Factors in 2005. We found that in Argentina, women who are poor, unmarried, unemployed or inactive, with lower levels of education and reduced access to health care, and women over the age of 65, were under-users of screening. Screening must not remain opportunistic. Strategies must incorporate the needs and perceptions of socially disadvantaged women, and increase their access to screening. Of utmost importance is to provide good quality screening and treatment services that reach women who are at risk. Pilot projects using new, alternative technologies should be encouraged in less developed parts of the country. Promotion among health professionals of the scientific basis and effectiveness of each screening modality is essential to reduce wasteful practices such as annual screening and screening of young women that waste resources and fail to reduce cervical cancer incidence and mortality rates.     

The impact of anti HPV vaccination on cervical cancer incidence and HPV induced cervical lesions: consequences for clinical management

Cervical cancer is the second most common cause of cancer-related deaths in women worldwide. Screening for cervical cancer is accomplished utilizing a Pap smear and pelvic exam. While this technology is widely available and has reduced cervical cancer incidence in industrialized nations, it is not readily available in third world countries in which cervical cancer incidence and mortality is high. Development of cervical cancer is associated with infection with high risk types of human papillomavirus (HPV) creating a unique opportunity to prevent or treat cervical cancer through anti-viral vaccination strategies. Several strategies have been examined in clinical trials for both the prevention of HPV infection and the treatment of pre-existing HPV-related disease. Clinical trials utilizing prophylactic vaccines containing virus-like particles (VLPs) indicate good vaccine efficacy and it is predicted that a prophylactic vaccine may be available within the next five years. But, preclinical research in this area continues in order to deal with issues such as cost of vaccination in underserved third world populations. A majority of clinical trials using therapeutic agents which aim to prevent the progression of pre-existing HPV associated lesions or cancers have shown limited efficacy in eradicating established tumors in humans possibly due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Future trends in clinical trials with therapeutic agents will examine patients with early stage cancers or pre-invasive lesions in order to prevent invasive cervical cancer. Meanwhile, preclinical studies in this field continue and include the further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. Given that cervical cancers are caused by the human papillomavirus, the prospect of therapeutic vaccination to treat existing lesions and prophylactic vaccination to prevent persistent infection with the virus are high and may be implemented in the near future. The consequences for clinical management may include a significant reduction in the frequency of Pap smear screening in the case of prophylactic vaccines, and the availability of less invasive and disfiguring treatment options for women with pre-existing HPV associated lesions in the case of therapeutic vaccines. Implementation of both prophylactic and therapeutic vaccine regimens could result in a significant reduction of health care costs and reduction of worldwide cervical cancer incidence.     

Risk Factors for Cervical Cancer by Histology

A case-control study in four Latin American countries enabled assessment of risk factors for different histologic types of invasive cervical cancers, with the main analyses focusing on 667 patients with squamous cell cancers and 43 with adenocarcinomas. The epidemiology of the squamous cell tumors resembled that found in other studies, namely a high risk associated with multiple sexual partners (RR = 1.5 for 2 vs 1), early ages at first intercourse (RR = 2.3 for <16 vs 20), history of a sexually transmitted disease (RR = 1.8), multiple births (RR = 2.2 for 7 vs 1-3), absence of prior Pap smear screening (RR = 3.0 vs Pap within 24 months), detection of HPV DNA (RR = 3.6), and limited years of schooling (RR = 1.9 for <4 vs 7). The adenocarcinomas appeared less affected by sexual, reproductive, or socioeconomic factors. There was no relationship with age at first intercourse, history of a sexually transmitted disease or education, and only marginal associations with number of sexual partners or parity. Absence of prior Pap smear screening as well as detection of HPV DNA, however, were associated with relationships equally strong as those for the squamous cell tumors. Oral contraceptive use distinctly affected risk of the adenocarcinomas, increasing risk by approximately two-fold. Analyses of the 18 subjects with adenosquamous cancer suggested some resemblance to the squamous cell tumors, especially with respect to the role of sexual and sociodemographic variables. These findings support the need for detailed studies of etiologic differences between the different histologic types of cervical cancers, with all emphasis on careful pathologic review and precise measurement of HPV.     

Harnessing the power of prevention: human papillomavirus vaccines

Human papillomavirus (HPV) infection and HPV-associated diseases pose a considerable health care burden in the United States. The morbidity and mortality associated with HPV infection and HPV-associated diseases, ranging from genital warts to cervical cancer, have prompted both the use of screening measures to monitor HPV infection and the development of numerous treatment modalities to address its clinical sequelae. Although screening programs have dramatically reduced the incidence of cervical cancer through early detection and treatment, this devastating illness, which frequently affects women of reproductive age, remains a major public health concern. Prophylactic vaccines that prevent HPV infection have proved to be safe, well tolerated, highly efficacious, and induce long-lasting immunity to HPV. Multivalent vaccines that protect against the most common disease-causing HPV types should significantly reduce the morbidity and mortality associated with HPV.     

Human papillomavirus

Human papillomaviruses are ancient small DNA viruses and represent the most common sexually transmitted infection in the world. In the majority, HPV infection is cleared by an incompletely understood immune response. HPV is a necessary but not sufficient cause of cervical cancer, and responsible for a proportion of other anogenital cancers including vulval, vaginal, anal and oropharyngeal. Oncogenesis is likely mediated through viral proteins which hijack host-cell machinery in epithelial keratinocytes and disrupt host tumour-suppressor proteins. Much work has been undertaken to further characterise the natural history of HPV infection and cervical disease. Such efforts have been translated to important public health interventions like the introduction of HPV tests in cervical screening. HPV vaccination programmes are expected to further reduce the incidence of high-risk HPV infections and resultantly HPV-related disease.     

Cervical cancer: effect of glandular cell type on prognosis,treatment, and survival

OBJECTIVE: To investigate survivals from cervical cancer, with special reference to effects of glandular histology and its influence on prognostic characteristics and management decisions. METHODS: Data on cervical cancers, diagnosed in 1984-2000, were obtained from the gynecologic oncology registry of hospitals of the University of Adelaide. Comparisons were made of disease-specific survival, age at diagnosis, diagnostic period, stage, grade, and primary course of treatment. RESULTS: The study included 544 squamous cell carcinomas, 43 adenosquamous carcinomas, five clear cell cancers, 136 other adenocarcinomas, and 19 cancers of "other" histological type. Overall survival was 72.2% at 5 years from diagnosis, decreasing to 67.5% at 15 years. Survival was lower for older ages, higher grades, and higher International Federation of Gynecology and Obstetrics stages, although equivalent for stages IIA and IIB. Unadjusted survivals varied by histological type (P =.001), with lower survivals suggested for adenosquamous and clear cell lesions and "other" histological types than for squamous cell carcinomas and other adenocarcinomas. After adjusting for age, stage, grade, and diagnostic period, adenocarcinomas had a higher case fatality than squamous cell lesions (relative risk 2.08, 95% confidence limit 1.35, 3.21), whereas the elevation in relative risk was lower and not statistically significant for a combined adenosquamous and clear cell category at 1.25 (0.69, 2.24). For stage II, both adenocarcinomas and the adenosquamous and clear cell group had lower survivals than squamous cell cancers. CONCLUSION: Relative to squamous cell carcinomas, adenocarcinomas and potentially adenosquamous cancers are becoming more common. This has implications for screening, treatment, and prognosis.     

Cervical cancer: the sub-Saharan African perspective

Cervical cancer is the second most common cancer in women worldwide and the leading cause of cancer deaths in developing countries. While incidence and mortality rates of cervical cancer have fallen significantly in developed countries, 83% of all new cases that occur annually and 85% of all deaths from the disease occur in developing countries. Cervical cancer is the most common cancer among women in sub-Saharan Africa. The incidence is on the increase in some countries. Knowledge and awareness of this disease on the continent are very poor and mortality still very high. Facilities for the prevention and treatment of cervical cancer are still very inadequate in many countries in the region. Governments in sub-Saharan Africa must recognise cervical cancer as a major public health concern and allocate appropriate resources for its prevention and treatment, and for research. Indeed, cervical cancer in this region must be accorded the same priority as HIV, malaria, tuberculosis and childhood immunisations.     

Prevalence of human papillomavirus types 16 and 18 in cervical adenocarcinoma and its precursors in Scottish patients

Our aim was to determine the prevalence of human papillomavirus (HPV) types 16 and 18 in cervical adenocarcinoma (and its precursors) in Scottish patients. Nucleic acid was extracted from paraffin-embedded, formalin-fixed tissues. We examined 119 cases of invasive adenocarcinoma, 20 cases of adenocarcinoma in situ, and 16 cases of normal glandular epithelium. HPV DNA was detected by polymerase chain reaction using type-specific primers for the E6 and E7 genes of HPV-16 and HPV-18 with conformation of HPV genotype by subsequent restriction fragment length polymorphism. HPV DNA was identified in 87 (62.6%) cases, with HPV-16 being detectable in 65 (47%) cases and HPV-18 in 41 (29%) cases. All the cases of normal tissue tested negative for HPV-16 and/or HPV-18. No significant relation between infecting HPV type (16 or 18) and subtypes of disease (within the invasive category and between the preinvasive and the invasive categories) was noted. Our findings support that HPV-16, along with HPV-18, are likely to play a significant role in the pathogenesis of cervical adenocarcinomas and that cervical cancer screening strategies that incorporate oncogenic HPV testing, and prophylactic vaccines that target these types, will be beneficial for the reduction of adenocarcinoma and associated glandular precursors.     

Adenocarcinoma of the uterine cervix: the presence of human papillomavirus and the method of detection

BACKGROUND: Effective screening programs have contributed to a decrease in the incidence of cervical squamous cell carcinomas but have had a limited sensitivity in the detection of adenocarcinoma precursor lesions. The aim of our study was to analyze cervical adenocarcinoma in greater detail: symptoms preceding the detection, the method of detection and the prevalence of human papillomavirus (HPV) with respect to age at diagnosis. MATERIAL AND METHODS: Clinical data were abstracted from the medical records of 82 women with pure invasive cervical adenocarcinomas. As diagnostic tools we used polymerase chain reaction (PCR)-based single-strand conformation polymorphism (SSCP) and/or direct DNA sequencing for HPV detection. RESULTS: Age at diagnosis predicting factors were HPV status, positive lymph nodes, histology and stage. HPV-negativity, lymph node metastases, advanced stage and poor differentiation were all associated with a high diagnostic age. In the multivariate analysis only HPV status was shown to have an independent impact on age at diagnosis, while stage showed only borderline significance. Twenty-three percent of the cancers were detected by screening and the remaining were due to different symptoms. Among the women considered, 93% had a normal Papanicolaou (Pap) smear 3 years before diagnosis and 60% within 1 year. There was no significant correlation between smoking, oral contraceptives and HPV-positivity. CONCLUSIONS: The absence of HPV was significantly associated with a high age at diagnosis. Pap screening had a limited effect in detecting adenocarcinoma at an early stage.     

Cervical cancer prevention: the impact of HPV vaccination

Cervical cancer remains a critical public health problem that is second only to breast cancer in overall disease burden for women throughout the world. In spite of the success of cervical cancer screening, Pap cytology screening is yet to be effectively implemented or has failed to reduce cervical cancer rates to an appreciable extent. Screening appears to benefit only a small fraction of women although a much larger percentage endures the inconvenience of the Pap test in order to avoid cervical cancer. The establishment of Human Papillomavirus (HPV) infection as the necessary cause of cervical precancers and cancers provides a tremendous opportunity for cervical cancer prevention through vaccination. HPV 16 and 18 which cause 70% of cervical cancers worldwide. Thus a prophylactic vaccine to prevent HPV related precancerous lesions and cancers would save lives, reduce the need for costly medical procedures and provide both women and communities throughout the world with substantial benefits. Based on the induction of neutralizing antibodies by non infectious Virus Like Particles (VLP) of L1 capside protein, prophylactic HPV vaccines have consistently induced high titter of neutralizing antibodies with minimal side effects and induce more than 90% protection from persistent HPV 16-18 infection and HPV 16 and 18 associated high-grade Cervical Intraepithelial Neoplasia (CIN) in proof of concept efficacy trials. HPV 16-18 vaccination will prevent HPV16-18 incident infection, and subsequently decrease in 90% the frequency of abnormal Pap attributable to these types and in about 50% overall abnormal Pap. HPV vaccination will reduce the number of women who require colposcopy, biopsy and cervical treatment for precancerous cervical lesions. The level of protection from death due to cervical cancer could exceed 95%. Three large phases prophylactic HPV VLP trials are now in progress and will form the basis for licensing of candidate vaccines in 2006. HPV vaccination targeting young female adolescents, aged 11 to 16 years, with a catch-up of those aged 17-25 years, would be a strategy to be addressed. Cervical cancer screening strategies, that will be cost-effective for the proper surveillance of women protected by HPV vaccination, are under analysis.