Implementation and evaluation of new methodologies for early diagnosis of high risk Human Papillomavirus Infection

• Author(s): Delgado, Cândida Filipa Abreu de Castro
• Date: 2009
• Persistent ID: http://hdl.handle.net/10451/1430
• Origin: Repositório da Universidade de Lisboa
• Subject(s): Biologia molecular; Papillomavírus humano; Teses de mestrado
• Document Type: Master thesis
• Language: English
• Advisor(s): Pista, Ângela Maria Chambel; Paulo, Octávio
• Contributor(s): Repositório da Universidade de Lisboa

Description

Tese de mestrado, Biologia (Biologia Humana e Ambiente), 2009, Universidade de Lisboa, Faculdade de Ciências

Cervical cancer is the second most common cancer in women worldwide. Persistent infection by high-risk human papillomavirus (HR-HPV) is considered to play a central role in cervical carcinogenesis. The aim of this work was the implementation and evaluation of new methodologies for early diagnosis of HR-HPV infection. Cervical samples, with or without cytological abnormalities, were tested for HPV DNA by different methods. Four studies were developed, namely, the prevalence of HPV infection among a group of Portuguese women, the evaluation of a new diagnostic system for HR-HPV detection, the implementation and evaluation of real-time PCR methodologies, and a case-study in women infected with HPV 16 and 18. Statistical analyses were done using SPSS version 16.0. Prevalence data showed that genital HPV infection is common among Portuguese women, with an overall positivity of 43.5%. This infection is frequent especially in younger women (25-29 years). The 4 most prevalent HR-HPV were HPV 16 (25.3%), HPV 31 (11.3%), HPV 51 (10.3%), and HPV 66 (9.1%). Evaluation of the new Abbott RealTime HR HPV suggests that this system is efficient, sensitive, specific, robust, reproducible, and suitable for HPV screening, particularly for prediction of premalignant lesions (CIN2+). The real-time PCR methodologies analysed for assessing the viral load, the DNA integration, and the RNAm transcript expression were highly reproducible and accurate for HPV results obtained in the case-study. Results seem to indicate that these methodologies are important for patient management and for cervical cancer prevention in women infected with HPV 16 and 18. In conclusion, the results obtained in this study can help to understand HPV epidemiology prevalence in Portugal and to identify molecular markers that can be used as predictors of premalignant and malignant lesion development, contributing for a decrease in morbidity and mortality rates of women infected by HR-HPV.

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