Efficacy, effectiveness and safety of HPV vaccination in women with conisation : a systematic review and meta-analyses

Cervical cancer is the fourth most common cancer affecting women worldwide. It is caused by persistent infection with oncogenic types of human papillomavirus (HPV). More than 200 types of HPV have been identified and more than 40 types of them infect the genital tract. HPV 16 and 18 are the two primary oncogenic types and are responsible for 71% of cervical cancers, and HPV 31, 33, 45, 52 and 58 together account for 18% of cervical cancers. While HPV infections are common and usually resolve without any consequences, persistent infections with highrisk HPV can progress to premalignant glandular or squamous intraepithelial lesions (cervical dysplasia). From a histopathological perspective, the squamous lesions are classified as cervical intraepithelial neoplasia (CIN) and graded as CIN 1 (mild dysplasia referring to low-grade squamous intraepithelial lesion [LSIL]), CIN 2 (moderate dysplasia referring to high-grade squamous intraepithelial lesion [HSIL]), and CIN 3 (severe dysplasia referring to HSIL, carcinoma in situ [CIS]). CIN 3+ includes CIN3 (CIS) and is, along with adenocarcinoma in situ (AIS), wellaccepted as the pathological state that immediately precedes invasive cervical cancer. HPV vaccination is an important measure to prevent cancer. In Europe, three HPV vaccines bivalent (Cervarix), quadrivalent (Gardasil 4) and nonavalent (Gardasil 9) are approved for use. All three vaccines target the high-risk oncogenic HPV types 16 and 18, and the nonavalent vaccine (Gardasil 9) also targets the five additional (oncogenic) HPV types 31, 33, 45, 52 and 58. Women diagnosed with CIN 2+ typically undergo cervical conisation (a surgical procedure) to remove precancerous cervical lesions to prevent disease progression. The administration of the HPV vaccine in women who have undergone conisation is grounded in the rationale of preventing reactivation or reinfections by the same HPV type, while also offering protection against new infections by other vaccine-targeted types. The objective of this review was to investigate the efficacy, effectiveness and safety of HPV vaccination in women undergoing conisation compared with those not receiving a HPV vaccination. HPV vaccination related to conisation was defined for the purposes of this study as HPV vaccine given shortly (i.e. four months or less) before, at or after conisation (as 'adjuvant' intervention to conisation, secondary prevention). We conducted meta-analyses separately for randomised controlled trial (RCTs) and non-randomised studies of the effects of interventions (NRSI).