Page 16 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

Chapter 1
Prevention of cervical cancer
Prevention of cervical carcinoma consists of two strategies: primary and secondary prevention. Primary prevention can be performed by HPV vaccination, but also by condom use to prevent HPV transmission. Secondary prevention can be performed by population screening for cervical cancer precursor lesions, followed by treatment.
Primary prevention of cervical carcinoma by HPV vaccination has been implemented in many countries worldwide. Young girls (and in some countries boys as well) are provided with either the bivalent vaccine, targeting HPV types 16 and 18, or the quadrivalent vaccine, which also protects against HPV types 6 and 11. Evidence has shown that vaccination of hrHPV negative women aged 15-26 years almost diminishes the incidence of HPV16/18 associated high-grade CIN lesions. The overall reduction of high-grade CIN, including lesions caused by other hrHPV types, is less substantial: the incidence of any high-grade CIN lesion in these women is reduced from 287 to 106/10.000 (RR 0.37).[19] Although implementation of HPV vaccination has indeed led to a significant reduction in the prevalence of HPV 16/18 in clinical practice, the effect is restrained by a limited vaccination coverage.[20] Vaccination uptake is hampered by perceived – but invalid – safety concerns, disbelief in vaccination efficacy, parental fear that vaccination might lead to more and/or riskier sexual behavior, but also by lack of insurance coverage.[21, 22] Worldwide, the vaccination rate ranges from 39-88% of the targeted population.[23] In the Netherlands, the uptake was only 61% in 2016.[24] It has been estimated that the coverage rate needs to be over 70% for girls aged 10-13 years, in order to substantially reduce the incidence of cervical cancer.[25] Consequently, the current vaccination program as a primary prevention strategy will not prevent all cases of HPV 16/18 induced CIN and cervical carcinoma. Moreover, the currently used bivalent and quadrivalent vaccines do not primarily protect against infection with other high-risk HPV types. A nonavalent vaccine, providing protection against HPV types 6/11/16/18/31/33/45/52/58, has recently been approved and is now commercially available. Studies indicate an increased prevention of high-grade CIN with the use of this vaccine, compared to the bivalent or quadrivalent alternatives. The proportion of additional cases potentially prevented by the nonavalent vaccine is estimated to be 19-33%, increasing protection against high-grade CIN up to 90%.[26, 27] However, this nonavalent vaccine is not currently used in vaccination programs and, like the other vaccines, does not provide complete protection against HPV induced cervical lesions. Therefore, additional strategies to prevent cervical carcinoma remain necessary. Condom use provides such a strategy, by prevention of HPV transmission during sexual intercourse. However, even consistent condom use does not provide optimal protection.[28] Consequently, not all cases of cervical carcinoma will be prevented by the current primary prevention options. Therefore, secondary prevention strategies remain necessary.
Secondary prevention can be performed by population screening for cervical abnormalities, followed by treatment of cervical cancer precursor lesions. Historically, cervical cancer screening was performed by cytological assessment of a cervical smear, followed by colposcopic evaluation when cytology revealed atypical cells. However, evidence has shown that primary HPV testing, followed by cytological evaluation upon the finding of a hrHPV infection, is a more effective
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