Page 125 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

as to whether CIN 2 actually corresponds to a well-defined phase of the pathogenetic pathway
of CIN, and consequently, whether it should be considered as an individual entity. Indeed, in the pathogenetic pathway of infection and transformation in CIN, the histological image of CIN2 may
represent the late stage of a productive infection or the early stage of a transforming infection,
which are considered two biologically different phases in the pathogenetic pathway of infection
and transformation.[31] Nevertheless, natural history studies, in which CIN2 and CIN3 lesions
were distinguished based on conventional pathological criteria, show a much higher spontaneous
regression rate for CIN2 (40-74%) than for CIN3 (22-33%).[6, 32] Other studies confirm the
high regression rate of CIN2 lesions.[33] Based on these results, guidelines now advice upon observational management of CIN2 in younger women, to reduce overtreatment and associated
long-term obstetric complications.[9] Despite the diagnostic difficulties, we do advocate the distinction of CIN2 and CIN3 lesions based on conventional histopathological criteria, with the
aim to provide young women with an opportunity for observational management in case of CIN2. 6 In this approach, any suspicion of CIN3 should lead to a CIN3 diagnosis, for safety concerns.
Strengths of this study include that it is the first study on prognostic factors in exclusively hrHPV positive CIN2, which makes the results applicable to current populations of women who participate in HPV-based screening for cervical cancer. Several limitations must be mentioned, however. First of all, only a limited number of women was available for inclusion in the study, as conservative management of CIN2 was less common in the past than currently. This may have prevented the finding of significant associations. A second limitation is the fact that our findings are based on a retrospective study of subjects at a single institution. Consequently, a selection bias cannot be ruled out. The findings of this study should therefore ideally be validated in a larger and prospective study. HPV genotyping was performed in the diagnostic biopsies, rather than in cytology specimen, as is performed in screening programs. By performing HPV genotyping in the biopsies, we ensured that the HPV genotype was actually the causative agent of the lesion.
In conclusion, we identified smoking status and parity as prognostic factors in the natural history of hrHPV positive CIN2, from a set of nine potential prognostic factors. These factors should be considered in individual patient counseling regarding the choice between immediate treatment or conservative management of hrHPV positive CIN2 lesions. Individual risk prediction could be further improved by the identification of additional prognostic factors. Further research thereto could focus on additional socio-demographic factors, such as sexual behavior, and on molecular markers of oncogenic processes.
Prognostic factors for hrHPV positive CIN2
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