CIN, cervical intraepithelial neoplasia, HPV, human papillomavirus.
was refined in the Bethesda III System (2001). According to this system, potentially premalignant squamous lesions fall into three categories: (i) atypical squamous cells (ASC), (ii) low-grade squamous intraepithelial lesions (LSIL), and (iii) high-grade squamous intraepithelial lesions (HSIL) (46). The ASC category is subdivided into two categories: those of unknown significance (ASC-US), and those in which high-grade lesions must be excluded (ASC-H). Low-grade squamous intraepithelial lesions include CIN 1 (mild dysplasia) and the changes of HPV, termed koilocytotic atypia. The HSIL category includes CIN 2 and CIN 3 (moderate dysplasia, severe dysplasia, and carcinoma in situ). A comparison of the various terms is shown in Table 19.1.
Cellular changes associated with HPV (i.e., koilocytosis and CIN 1) are incorporated within the category of LSIL because the natural history, distribution of various HPV types, and cytologic features of both of these lesions are the same (27). Long-term follow-up studies showed that lesions properly classified as koilocytosis progress to high-grade intraepithelial neoplasia in 14% of cases and that lesions classified as mild dysplasia progress to severe dysplasia or CIS in 16% of cases (4,46). It was initially thought that lesions classified as koilocytosis would contain only low-risk HPV types, such as HPV-6 and -11, whereas high-risk HPV types, such as HPV-16 and -18, would be limited to true neoplasms, including CIN 1, thus justifying the distinction. Histopathologic and molecular virologic correlation showed a similar heterogeneous distribution of low-and high-risk HPV types in both koilocytosis and CIN 1 (47). Studies evaluating the dysplasia, CIS, and CIN terminology consistently demonstrated problems with interobserver and intraobserver reproducibility (48). The greatest lack of reproducibility is between koilocytosis and CIN 1 (49). On the basis of clinical behavior, molecular biologic findings, and morphologic features, HPV changes and CIN 1 appear to be the same disease.
The rationale for combining CIN 2 and CIN 3 into the category of HSIL is similar. The biologic studies reveal a comparable mix of high-risk HPV types in the two lesions, and the separation of the lesions is not reproducible (48,49). The management of CIN 2 and CIN 3 is similar.