Implementation of HPV tests in Latin America: what we learned; what should we have learned, and what can we do better?

Cervical cancer is caused by HPV. Although it is the fourth most common type of cancer diagnosed and the fourth cause of cancer death, cervical cancer is nearly completely preventable because of the vaccination and screening available. The present review aims to map the initiatives conducted to implement or evaluate the implementation of HPV testing in Latin American countries. We performed the review by searching on PubMed in the English language and on grey literature, as most of the information about the guidelines used was found in governmental websites in the Spanish language. We only found information in eight countries concerning HPV testing as primary screening. Only Mexico has established HPV-based screening in all territories. There are three countries with regional implementation. Two countries with pilot studies indicated results that supported implementation. Finally, there are another two countries with a national recommendation. We have learned that HPV implementation is feasible and a very promising tool for reducing cervical cancer morbidity and mortality. The costs associated with saving lives and reducing suffering due to morbidity of a preventable disease must be pragmatically evaluated by the Latin America governments, and improving outcomes must be a mandatory priority for those that are responsible for addressing an organized system of cervical cancer screening.This research was funded by the São Paulo Research Foundation (FAPESP), grant number 2020/00445-6 and 2018/22017-6

Self-collection for high-risk HPV detection in Brazilian women using the care HPV™ test

Cervical cancer is the second most common cancer among Brazilian women. High-risk human papillomavirus (hr-HPV) persistence is the primary cause of cervical neoplasia. Early detection of hr-HPV is important for identifying women at risk for developing cervical lesions. Approximately 85% of new cases of cervical cancer worldwide and 50% of the total cervical cancer deaths occurred in developing countries. Here, a new methodology to support a cervical cancer screening program was evaluated in women from various Brazilian regions. METHODS: Two thousand women aged 18-77years were enrolled in an opportunistic cervical cancer screening program and were randomized into self-vaginal or health professional-guided cervical sampling groups. The Qiagen careHPV™ test was performed on all samples. Pap tests were performed on all women using liquid-based cytology. RESULTS: Positive hr-HPV results were obtained in 12.3% (245/2000) of women; similar rates were observed in self- or health professional-collected samples. Eighty-nine percent (1719/2000) of cervical cytologies classified as normal were negative to hr-HPV. Among the cytological samples, 36.6% classified as ASC-US+ were positive to hr-HPV, 78.8% were LSIL and 75.0% were HSIL. CONCLUSIONS: Self-sampled and health professional-sampled vaginal/cervical specimens did not differ in their rates of detection of hr-HPV. Therefore, HPV DNA testing in self-sampled vaginal cells is an alternative to primary screening in low-resource settings.The authors thank the following: Cancer Prevention Department Team, Cleyton Zanardo de Oliveira and Allini Mafra of the Researcher Support Team and the Pathology Depai Intent of the Barretos Cancer Hospital. Rui Manuel Reis and Andre Lopes Carvalho from the Molecular Oncology Center; Jose Eduardo Levi from Sao Paulo University; Cintia B. Oliveira, Raphael Haikel junior and Edmundo Mauad from Barretos Cancer Hospital. Luisa Lina Villa was supported by a grant from CNPq and FAPESP (INCT-HPV). Study Supported by CNPq - Process no 573799/2008-3 and FAPESP no 2008/57889-1. They also thank all volunteer women who participated of this study

The Role of Self-Collection by Vaginal Lavage for the Detection of HPV and High-Grade Intraepithelial Neoplasia

The Role of Self-Collection by Vaginal Lavage for the Detection of HPV and High-Grade Intraepithelial NeoplasiaObjective: To compare the results of cervical cytology and high-risk HPV tests using samples obtained using two different collection modalities in a population of Brazilian women: self-collection (vaginal lavage) and cervical Pap testing. Methods: We enrolled 204 women who were aged 18-64 years and had previously obtained abnormal cervical cytology test results; 83.8% of them agreed to participate. The sample was divided into two aliquots: one for the cytological study and one for the molecular analysis of high-risk HPV. Results: Fifty-eight percent of the participants preferred to utilize self-collection as an alternative screening method. However, we noticed that the HPV positivity rate was significantly lower in self-collected samples when compared to those obtained using the conventional collection method (p = 0.035). The cytology tests of the samples obtained via self-collection were sensitive and had a positive predictive value and an area under the curve (AUC) that were significantly lower than those of the Pap test. However, the specificity and negative predictive value of these tests were similar. When compared with the HPV test, the self-collected samples demonstrated lower accuracy in predicting high-grade cervical intraepithelial neoplasia or worse, with a significantly lower sensitivity, positive predictive value, and AUC than the cervical Pap test samples. Conclusion: Self-collection by vaginal lavage is simple and well accepted by women. Due to its limitations, however, self-collection by lavage should be utilized with caution.info:eu-repo/semantics/publishedVersio

Management of early-stage vulvar cancer

Vulvar cancer is a rare gynecological malignancy since it represents 4% of all cancers of the female genital tract. The most common histological type is squamous cell carcinoma (90%). This type can be classified into two clinicopathological subtypes according to the etiology. The first subtype is associated with persistent human papillomavirus infection and is usually diagnosed in younger women. The second subtype is associated with lichen sclerosus condition, and in most cases is diagnosed in postmenopausal women. Currently, an increase in first subtype cases has been observed, which raised the concern about associated mortality and treatment morbidity among young women. Vulvar cancer treatment depends on histopathology grade and staging, but surgery with or without radiotherapy as adjuvant treatment is considered the gold standard. In recent decades, sentinel lymph node biopsy has been incorporated as part of the treatment. Therefore, we sought to review and discuss the advances documented in the literature about vulvar cancer focusing on the treatment of early-stage disease. Relevant articles, such as the GROINS-V studies and the GOG protocols, are presented in this review. Additionally, we discuss key points such as the evolution of treatment from invasive surgery with high morbidity, to more conservative approaches without compromising oncologic safety; the role of sentinel lymph node mapping in the initial staging, since it reduces the complications caused by inguinofemoral lymphadenectomy; the recurrences rates, since local recurrence is common and curable, however, groin-associated, or distant recurrences have a poor prognosis; and, finally, the long-term follow-up that is essential for all patients.This study was partially supported by Public Ministry of Labor Campinas (Research, Prevention and Education of Occupational Cancer, Brazil) and the Barretos Cancer Hospital

Clinical characteristics of women diagnosed with carcinoma who tested positive for cervical and anal high-risk human papillomavirus DNA and E6 RNA

High-risk human papillomavirus (hrHPV) is an essential cause of cervical carcinoma and is also strongly related to anal cancer development. The hrHPV E6 oncoprotein plays a major role in carcinogenesis. We aimed to evaluate the frequency of hrHPV DNA and E6 oncoprotein in the anuses of women with cervical carcinoma. We analyzed 117 women with cervical cancer and 103 controls for hrHPV and the E6 oncogene. Positive test results for a cervical carcinoma included 66.7 % with hrHPV-16 and 7.7 % with hrHPV-18. One case tested positive for both HPV variants (0.9 %). The samples from the anal canal were positive for HPV-16 in 59.8 % of the cases. Simultaneous presence of HPV in the cervix and anal canal was found in 53.8 % of the cases. Regarding expression of E6 RNA, positivity for HPV-16 in the anal canal was found in 21.2 % of the cases, positivity for HPV-16 in the cervix was found in 75.0 %, and positivity for HPV-18 in the cervix was found in 1.9 %. E6 expression in both the cervix and anal canal was found in 19.2 % of the cases. In the controls, 1 % tested positive for HPV-16 and 0 % for HPV-18. Anal samples from the controls showed a hrHPV frequency of 4.9 % (only HPV16). The presence of hrHPV in the anal canal of women with cervical cancer was detected at a high frequency. We also detected E6 RNA expression in the anal canal of women with cervical cancer, suggesting that these women are at risk for anal hrHPV infection.We acknowledge the Research Support Fund of the State of São Paulo (FAPESP), process number 2010/16795–4), for the financial support grants. FAPESP had no other type of influence on this manuscript beyond the financial suppor

Organized Cervical Cancer Screening Program in Barretos, Brazil: Experience in 18 Municipalities of São Paulo State

The aim of this report is to demonstrate the Barretos Cancer Hospital initiative of organizational, laboratorial, and human resources training in the implementation of an organized cervical screening program in low-resource settings.Objectives: The aim of this report is to demonstrate the Barretos Cancer Hospital initiative of organizational, laboratorial, and human resources training in the implementation of an organized cervical screening program in low-resource settings. Methods: We developed a computational program to report all epidemiological, clinical, and laboratorial findings, and to trace all necessary information to recruit women for regular screening or for referral for complementary exams after liquid-based Pap test analyses. Results: All Pap tests were collected in liquid medium and in 2014 more than 160,000 tests were analyzed and 2,900 colposcopy examinations were performed. From 2012 to 2015, the percentage of exams collected increased from 54.6% in 2012 to 62.4% in 2013, 68.4% in 2014, and 71% in 2015. Per 1,000 Pap tests, 0.4 cases of invasive cancer were diagnosed; for in situ carcinoma, 1.9 cases were identified. More importantly, between 2011 and 2015, 89.4% of all carcinomas were detected at clinical stage 0 or I (in situ carcinoma), and only 5% at stages III and IV. Conclusions: Since the organized system was implemented, 98% of women have attended their recall for colposcopy. So far, we have not reached the target of 70% of women for this proposal, as recommended by the international standards.info:eu-repo/semantics/publishedVersio

Seasonal profile and level of CD4+ lymphocytes in the occurrence of cryptosporidiosis and cystoisosporidiosis in HIV/AIDS patients in the Triângulo Mineiro region, Brazil

Patients with AIDS are particularly susceptible to infection with intestinal coccidia. In this study the prevalence of infections with Cryptosporidium sp and Cystoisospora belli were evaluated among HIV/AIDS patients in the Triângulo Mineiro region, Brazil. Between July 1993 and June 2003 faecal samples from 359 patients were collected and stained by a modified Ziehl-Neelsen method, resulting in 19.7% of positivity for coccidian (8.6% with Cryptosporidium sp, 10.3% with Cystoisospora belli and 0.8% with both coccidian). Patients with diarrhoea and T CD4+ lymphocyte levels < 200 cells/mm3 presented higher frequency of these protozoans, demonstrating the opportunistic profile of these infections and its relationship with the immunological status of the individual. It was not possible to determine the influence of HAART, since only 8.5% of the patients positive for coccidian received this therapy regularly. Parasitism by Cryptosporidium sp was more frequent between December and February and thus was characterised by a seasonal pattern of infection, which was not observed with Cystoisospora belli

Methylation of the hsa-miR-124, SOX1, TERT, and LMX1A genes as biomarkers for precursor lesions in cervical cancer

The methylation profile of genes in precursor lesions in cervical cancer was characterized to improve screening techniques for high-grade intraepithelial neoplasia.Objectives The methylation profile of genes in precursor lesions in cervical cancer was characterized to improve screening techniques for high-grade intraepithelial neoplasia. Methods A total of 447 cervical cytology samples obtained from women who underwent colposcopy were examined. The cases were distributed as follows: (1) cervices without cervical intraepithelial neoplasia (CIN; n = 152); (2) cervices with a CIN grade of 1 (CIN 1; n = 147); and (3) cervices with a CIN grade of 2 or 3 (CIN 2/3; n = 148). The methylation pattern for a panel of 15 genes was analysed by quantitative methylation-specific PCR (qMSP) and compared between the groups (≤CIN 1 vs. CIN 2+). Results In the validation set, seven genes presented significantly different methylation profiles according to diagnosis, namely, DAPK1 (p = 0.001), EPB41L3 (p = 0.001), HIC1 (p = 0.028), hsa-miR-124-2 (p = 0.001), LMX1A (p = 0.001), SOX1 (p = 0.001), and TERT (p = 0.001). Six genes showed a significant increase in the frequency of methylation in the presence of hr-HPV, namely, DAPK1 (p = 0.001), EPB41L3 (p = 0.001), hsa-miR-124-2 (p = 0.001), LMX1A (p = 0.001), SOX1 (p = 0.001), and TERT (p = 0.001). The methylation of the hsa-miR-124 gene showed sensitivity and specificity (86.7% and 61.3%, respectively) similar to that of the HPV test (91.3% and 50.0%, respectively). The independent factors associated with the diagnosis of CIN 2+ and the methylation of the hsa-miR-124-2 (OR = 5.1), SOX1 (OR = 2.8), TERT (OR = 2.2), and LMX1A (OR = 2.0) genes were a positive test for hr-HPV (odds ratio [OR] = 5.5). Conclusions Hypermethylation of the hsa-miR-124-2, SOX1, TERT, and LMX1A genes may be a promising biomarker for precursor lesions in cervical cancer regardless of the hr-HPV status.São Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo–FAPESP) with the cooperation of the Coordination for the Improvement of Higher Education Personnel (Conselho Nacional de Desenvolvimento Científico e Tecnológico–CNPq-PPSUS) (Protocol Nos. 12/51221-4, 14/50014-0, 14/24415-8, and 15/15065-6), the National Institute of Science and Technology (Instituto Nacional de Ciência e Tecnologia–INCT-HPV) (FAPESP Proc. No. 2008/578891 and CNPq Proc. No. 573799/2008-3), and CAPES (PROSUP/CAPES Protocol No. 1571815)info:eu-repo/semantics/publishedVersio