Human papillomavirus (HPV) screening and cervical cancer burden. A Brazilian perspective

This review tackles the issues related to disease burden caused by cervical cancer (CC) and its precursor (CIN) lesions in Brazil. A special focus is given to new technologies with potential to interfere with the development of CC by reducing the high-risk human papillomavirus (hr-HPV)-induced lesions that remain a major public health burden in all developing countries where organized screening programs do not exist. Globally, 85 % of all incident CC and 50 % of CC deaths occur in the developing countries. Unfortunately, most regions of Brazil still demonstrate high mortality rates, ranking CC as the second most common cancer among Brazilian women. Recently, CC screening programs have been tailored in the country to enable early detection of CC precursor lesions and thereby reduce cancer mortality. A combination of HPV testing with liquid-based cytology (LBC) seems to be a promising new approach in CC screening, with high expectation to offer an adequate control of CC burden in this country.

HPV DNA testing with cytology triage in cervical cancer screening: Influence of revealing HPV infection status

BACKGROUND: Knowledge of cervical human papillomavirus (HPV) status might influence a cytotechnician's assessment of cellular abnormalities. The authors compared original cytotechnicians' Papanicolaou (Pap) readings for which HPV status was concealed with Pap rereads for which HPV status was revealed separately for 3 screening populations. METHODS: Previously collected cervical Pap smears and clinical data were obtained from the Canadian Cervical Cancer Screening Trial (study A), the Democratic Republic of Congo Community-Based Screening Study (study B), and the Brazilian Investigation into Nutrition and Cervical Cancer Prevention (study C). Smears were reread with knowledge of HPV status for all HPV-positive women as well as a sample of HPV-negative women. Diagnostic performance of Pap cytology was compared between original readings and rereads. RESULTS: A total of 1767 Pap tests were reread. Among 915 rereads for HPV-positive women, the contrast between "revealed" and "concealed" Pap readings demonstrated revisions from negative to positive results for 109 women (cutoff was atypical squamous cells of undetermined significance or worse) and 124 women (cutoff was low-grade squamous intraepithelial lesions [LSIL] or worse). For a disease threshold of cervical intraepithelial neoplasia of grade 2 or worse, specificity significantly declined at the atypical squamous cells of undetermined significance cutoff for studies A (86.6% to 75.3%) and C (42.5% to 15.5%), and at the LSIL cutoff for study C (61.9% to 37.6%). Sensitivity remained nearly unchanged between readings, except in study C, in which reread performance was superior (91.3% vs 71.9% for the LSIL cutoff). CONCLUSIONS: A reduction in the diagnostic accuracy of Pap cytology was observed when revealing patients' cervical HPV status, possibly due to a heightened awareness of potential abnormalities, which led to more false-positive results. Cancer (Cancer Cytopathol) 2015. (c) 2015 American Cancer Society.

Historical analysis of the Brazilian cervical cancer screening program from 2006 to 2013: a time for reflection

BACKGROUND: The Cervical Cancer Database of the Brazilian National Health Service (SISCOLO) contains information regarding all cervical cytological tests and, if properly explored, can be used as a tool for monitoring and managing the cervical cancer screening program. The aim of this study was to perform a historical analysis of the cervical cancer screening program in Brazil from 2006 to 2013. MATERIAL AND METHODS: The data necessary to calculate quality indicators were obtained from the SISCOLO, a Brazilian health system tool. Joinpoint analysis was used to calculate the annual percentage change. RESULTS: We observed important trends showing decreased rates of low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and an increased rate of rejected exams from 2009 to 2013. The index of positivity was maintained at levels below those indicated by international standards; very low frequencies of unsatisfactory cases were observed over the study period, which partially contradicts the low rate of positive cases. The number of positive cytological diagnoses was below that expected, considering that developed countries with low frequencies of cervical cancer detect more lesions annually. CONCLUSIONS: The evolution of indicators from 2006 to 2013 suggests that actions must be taken to improve the effectiveness of cervical cancer control in Brazil.

Human papillomavirus infection and cervical cancer in Brazil: a retrospective study

Two hundred and thirty paraffin-embedded biopsies obtained from female cervical lesions were tested for the presence of human papillomavirus (HPV) types 6/11,16/18 and 31/33/35 DNA using non-isotopic in situ hybridization. Specimens were classified according to the Bethesda System in low grade squamous intraepithelial lesion (LSIL), high grade SIL (HSIL) and squamous cell carcinoma (SCC). HPV prevalence ranged from 92.5% in LSIL to 68.5% in SCC. Benign types were prevalent in LSILs while oncogenic types infected predominantly HSILs and SCC. HPV infection showed to be age-dependent, but no significant relation to race has been detected. Patients were analyzed through a five-year period: 20.7% of the lesions spontaneously regressed while 48.9% persisted and 30.4% progressed to carcinoma. Patients submitted to treatment showed a 19.4% recurrence rate. High risk types were present in 78.6% (CrudeOR 13.8, P=0.0003) of the progressive lesions, and in 73.7% of the recurrent SILs (COR 19.3, P=0.0000001). Possible co-factors have also been evaluated: history of other sexually transmitted diseases showed to be positively related either to progression (Adjusted OR 13.0, P=0.0002) or to recurrence (AOR 17.2, P=0.0002) while oral contraceptive use and tobacco smoking were not significantly related to them (P>0.1). Association of two or more co-factors also proved to be related to both progression and recurrence, indicating that they may interact with HPV infection in order to increase the risk of developing malignant lesions.

Breast and cervical cancer screening programme implementation in 16 countries.

OBJECTIVES: There is a continuing need to monitor and evaluate the impact of organized screening programmes on cancer incidence and mortality. We report results from a programme assessment conducted within the International Cancer Screening Network (ICSN) to understand the characteristics of cervical screening programmes within countries that have established population-based breast cancer screening programmes. METHODS: In 2007-2008, we asked 26 ICSN country representatives to complete a web-based survey that included questions on breast and cervical cancer screening programmes. We summarized information from 16 countries with both types of organized programmes. RESULTS: In 63% of these countries, the organization of the cervical cancer screening programme was similar to that of the breast cancer screening programme in the same country. There were differences in programme characteristics, including year established (1962-2003 cervical; 1986-2002 breast) and ages covered (15-70+ cervical; 40-75+ breast). Adoption of new screening technologies was evident (44% liquid-based Pap tests; 13% human papillomavirus (HPV)-triage tests cervical; 56% digital mammography breast). There was wide variation in participation rates for both programme types (<4-80% cervical; 12-88% breast), and participation rates tended to be higher for cervical (70-80%) than for breast (60-70%) cancer screening programmes. Eleven ICSN member countries had approved the HPV vaccine and five more were considering its use in their organized programmes. CONCLUSION: Overall, there were similarities and differences in the organization of breast and cervical cancer screening programmes among ICSN countries. This assessment can assist established and new screening programmes in understanding the organization and structure of cancer screening programmes.

A Review of the Bio-medical Evidence on Breast, Ovarian and Cervical Cancer

This review aims to provide good quality, up-to-date biomedical evidence of the therapies available to women in Ireland to treat breast, cervical and ovarian cancer. This review summarises evidence from guidelines and high quality studies. It should be noted however that scientific evidence is not infallible, and knowledge in this field is constantly evolving. The evidence summarised in this review presents the current consensus. Download document here   Download summary of report

Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia, Brazil

This study estimated the prevalence and distribution of human papillomavirus (HPV) types among women with cervical intraepithelial neoplasia (CIN) grade III and invasive cervical cancer from Goiás (Brazil Central Region). Seventy-four cases were analyzed and consisted of 18 CIN III, 48 squamous cell carcinomas, 4 adenocarcinomas, 1 adenosquamous carcinoma and 3 undifferentiated carcinomas. HPV-DNA sequences were examined in formalin-fixed and paraffin-embedded tissues using primers from L1 region GP5+/GP6+. Polymerase chain reaction products were typed with dot blot hybridization using probes for HPV 16, 18, 31, 33, 45, 54, 6/11, 42/43/44, 51/52, 56/58. The prevalence of HPV was estimated to be 76% (56/74). HPV 16 was the most frequently found type, followed by HPV 33, 18 and 31. The prevalence of untyped HPV was 6%; 79% percent of the squamous cell carcinoma cases and 61% percent of the CIN III were positive for HPV and the prevalence rate of HPV types was the same for the total number of cases. According to other studies, HPV type 16 is the most prevalent virus in all Brazilian regions, but there is variation regarding to other types. Type 18 is the second most prevalent HPV in North, Southeast and South Brazil regions and types 31 and 33 are the second most prevalent HPV in Northeast and Central Brazil, respectively.

Beating cervical cancer: information for girls in Year 9, aged 12-13 (English and eight translations)

This leaflet is distributed to girls in Year 9 and explains about the HPV vaccine which can help protect against cervical cancer.

Beating cervical cancer. The HPV vaccine - questions and answers for parents of girls in Year 9 (English and eight translations)

This leaflet provides more detailed information in a question and answer format about the HPV vaccine offered to girls in Year 9 which can help protect against cervical cancer.

Cervical cancer: it's best to take the test

From January 2011, the Northern Ireland cervical screening programme no longer invited women aged under 25 to attend for screening. In addition, the screening interval for women aged 25-49 was reduced to every three years. This leaflet is one of a series of new information materials that was developed to reflect the policy changes and to give information to increase the uptake of information and interventions offered to protect and maintain the health of women in the target group. It gives information about cervical screening in Northern Ireland and helps women to understand why it is important to be screened.

Beating cervical cancer. The HPV vaccine - questions and answers for parents of girls in Year 9 (English and eight translations)

This leaflet provides more detailed information in a question and answer format about the HPV vaccine offered to girls in Year 9 which can help protect against cervical cancer.

Beating cervical cancer: information for girls in Year 9, aged 12-13 (English and eight translations)

This leaflet is distributed to girls in Year 9 and explains about the HPV vaccine, which can help protect against cervical cancer.

Cervical cancer: it's best to take the test (English and 11 translations)

Testing for high-risk human papillomavirus (HR-HPV) as triage and test of cure was introduced into the Northern Ireland Cervical Screening Programme on Monday 28 January 2013. This policy change will significantly alter the screening pathway for women with a mild dyskaryosis or borderline smear result.

HPV vaccination: the beginning of the end of cervical cancer? - A Review

Human papillomavirus (HPV) is responsible for all cases of cervical cancer, as well as a great percentage of other anogenital tumors and oropharyngeal tumors. Since the main etiologic factor for these diseases is a virus, prophylactic measures are the best way to reduce the burden caused by the infection and associated disease. This review brings up to date information on the two commercially available prophylactic HPV vaccines against HPV, as well as presenting the ongoing research on HPV peptide, protein and dendritic cell based therapeutic vaccines.

High prevalence and low E6 genetic variability of human papillomavirus 58 in women with cervical cancer and precursor lesions in Southeast Mexico

Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer (CC). Throughout the world, HPV type 58 prevalence varies from one region to another; it is higher in women from certain countries in Asia and Latin America, such as China and Mexico. Although intratypic variants have been reported on a few occasions, our knowledge about HPV 58 genetic variation remains limited. Therefore, this work aims to (i) determine the prevalence of HPV type 58 amongst Mexican women with invasive CC or precursor lesions and (ii) identify HPV 58 sequence variants. One hundred and forty five colposcopy clinic patients were studied. Genotyping of HPV 16, 18 and 58 was determined by specific nested PCR and HPV 58 variants were detected by direct sequencing. The general prevalence of HPV was 51.7% (75/145). HPV 16 was found in 30.6% (23/75) and HPV 58 in 24% (18/75) of the patients. HPV 18 was not identified in patients with cervical intraepithelial neoplasia (CIN) grade I; it was only found in those with CIN II, with a prevalence of 6.8% (3/44). In patients with CC, the prevalence of HPV 16 and 58 was 78.9%. Regarding HPV 58 variants, 94.4% of the HPV 58 sequences were identical to the prototype strain, whereas one sample showed changes at a single nucleotide. This study demonstrates a high prevalence of HPV 58 and a low genetic variability of E6 sequences amongst Mexican colposcopy patients.