General introduction and thesis outline 23 1 latency period (i.e., from the onset of a transforming hrHPV infection it may take another 20 to 30 years before cervical cancer may develop 13), there is a window of opportunity to identify lesions early and effectively treat them to prevent cancer development 80. Cervical screening programs have been implemented worldwide since the mid-20th century. For several decades, cytology-based screening has been the cornerstone of cervical cancer prevention relying on microscopic evaluation of cervical cells. Different classification systems are in use to define the severity of cytological abnormalities found in cervical cytology preparations, for example the Bethesda 2001 and CISOE-A classification (Table 1.1) 81. Cytology-based cervical screening programs have led to a notable decrease in cervical cancer incidence and mortality in many countries 82-86. Cervical cancer screening revolutionised by the discovery of HPV as the main causative agent of the disease. Over the last decade, many countries have transitioned from cytology-based screening to primary HPV-based screening, to obtain better detection of cervical cancer and its high-grade precursor lesions 87-92. Large randomised controlled trials (RCTs) have shown that HPV screening leads to earlier detection of clinically relevant lesions compared to cytology and provides a 60 – 70% better protection against invasive cervical cancer 87, 89, 90, 92-96. The high accuracy and reproducibility of HPV testing has led to the replacement of cytology, along with an extension of screening intervals for women with a negative screening result 87, 97-101. Description* Inadequate Normal Borderline dyskaryosis Mild dyskaryosis Moderate dyskaryosis Severe dyskaryosis Carcinoma in situ Carcinoma CISOE-A C0 S1, O1, E1-2 S1, O2, E1-2 S2-3, O3, E3 S4, E4-5 S5, O4-5 S6, O6, E6 S7, E7 S8-9, O7-8, E9 Pap-score Pap 0 Pap 1 Pap 2 Pap 3a1 Pap 3a2 Pap 3b Pap 4 Pap 5 Bethesda 2001 Unsatis- factory for evaluation NILM Atrophy ASC-H HSIL or >BMD SCC BMD ASC-US LSIL AGC favour neoplastic CIS / AIS AC Abbreviations: CISOE-A: C, composition; I, inflammation; S, squamous epithelium; O, other abnormalities and endometrium; E, endocervical columnar epithelium; A, adequacy; BMD, borderline or mild dyskaryosis; CIS, carcinoma in situ; Pap, Papanicolaou; NILM, negative for intraepithelial lesion or malignancy; ASC-H, atypical squamous cells cannot exclude HSIL; HSIL, high-grade intraepithelial lesion; ASC-US, atypical squamous cells of undetermined significance; AGC, atypical glandular cells; LSIL, low-grade intraepithelial lesion; HSIL, high-grade intraepithelial lesion; AIS, endocervical adenocarcinoma in situ; SCC, squamous cell carcinoma; AC, adenocarcinoma Table 1.1 Classification of cervical cytology (adapted from Bulk et al., 2004 81).
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