title: Effectiveness of HPV vaccination in women reaching screening age in Italy.
abstract: A randomized trial was conducted in Tuscany, Italy, to evaluate the effectiveness of HPV vaccination for 25year old (yo) women who attend at the first time cervical cancer screening. The trial also evaluated immune response after vaccination, reductions of cytological abnormalities and the impact of vaccination on screening activity.
  
  
  
  During 2010-2011, all 25 yo women who were invited to the Florence cervical cancer screening programme were also asked to participate in the trial. Enrolled women were randomized into study and control groups. Those in the study group were offered HPV vaccination after the usual Pap test. The cytology distribution and prevalence for any high risk (hr) HPV type were compared at the subsequent screening round in an intention-to-treat analysis. The impact of HPV vaccination was evaluated per protocol comparing vaccinated women with the control group.
  
  
  
  Our results showed a reduction in HPV prevalence at recall for any hr-HPV type but it was not statistically significant, being 17.1% vs 21.4%, p=0.20 in the study and control groups, respectively. If we restricted the analysis to vaccinated women, strong reductions of the HPV 16,18,31,33,45 and HPV 31,33,45 infections were observed, being 5.3% vs 12.8%, p<0.01 and 2.1% vs 6.5%, p=0.02, respectively. Significant reductions for any hr-HPV infection and for HPV 16 infection were also observed in women HPV 16/18 negative at enrolment, being 12% vs 21.4%, p<0.01 and 0.6% vs 6.7%, p-value<0.01, respectively. In women hr-HPV negative at enrolment no infections due to HPV 16 or HPV 18 were observed and there was a big reduction for any hr-HPV infection (7.1% vs 21.4% p<0.01). A strong antibody response was observed not only for HPV 16 & 18 but also for their related types.
  
  
  
  Our findings suggest that HPV vaccination at the age 25 is beneficial if it is offered to hr-HPV negative women. Our data will assist in developing a cost effectiveness model for choosing the best strategy to integrate screening and vaccination for the coming years. Clinical trial registration number is NCT02296255.
authors.affiliation: Cancer Prevention Laboratory, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio, 2-50139 Florence, Italy. Electronic address: f.carozzi@ispo.toscana.it.
authors.forename: F M
authors.initials: FM
authors.lastname: Carozzi
authors.affiliation: Clinical and Descriptive Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via delle Oblate, 4-50141 Florence, Italy. Electronic address: c.ocello@ispo.toscana.it.
authors.forename: C
authors.initials: C
authors.lastname: Ocello
authors.affiliation: Cancer Prevention Laboratory, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio, 2-50139 Florence, Italy. Electronic address: e.burroni@ispo.toscana.it.
authors.forename: E
authors.initials: E
authors.lastname: Burroni
authors.affiliation: Department of Medical Microbiology, Malmo University Hospital, Lund University, Malmo, Sweden(2). Electronic address: helena.faust@ki.se.
authors.forename: H
authors.initials: H
authors.lastname: Faust
authors.affiliation: Clinical and Descriptive Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via delle Oblate, 4-50141 Florence, Italy. Electronic address: m.zappa@ispo.toscana.it.
authors.forename: M
authors.initials: M
authors.lastname: Zappa
authors.affiliation: Clinical and Descriptive Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via delle Oblate, 4-50141 Florence, Italy. Electronic address: paci.eugenio@gmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Paci
authors.affiliation: Screening Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio, 2-50139 Florence, Italy. Electronic address: a.iossa@ispo.toscana.it.
authors.forename: A
authors.initials: A
authors.lastname: Iossa
authors.affiliation: Department of Health Sciences, University of Florence, Viale Pieraccini, 6-50139 Florence, Italy. Electronic address: p.bonanni@unifi.it.
authors.forename: P
authors.initials: P
authors.lastname: Bonanni
authors.affiliation: Cancer Prevention Laboratory, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio, 2-50139 Florence, Italy. Electronic address: m.confortini@ispo.toscana.it.
authors.forename: M
authors.initials: M
authors.lastname: Confortini
authors.affiliation: Cancer Prevention Laboratory, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio, 2-50139 Florence, Italy. Electronic address: c.sani@ispo.toscana.it.
authors.forename: C
authors.initials: C
authors.lastname: Sani
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D003362:Cost-Benefit Analysis; D055088:Early Detection of Cancer; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D007558:Italy / Q000453:epidemiology; D065006:Papanicolaou Test; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage*; D015995:Prevalence; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination / Q000191:economics; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines
keywords: 25-year-old women; Cervical cancer screening; Cytological abnormalities; HPV; HPV vaccination; Immune response