Effect of HPV Vaccination on Women Aged 25 Years
Condition: Cervical Cancer
MeSH terms: Uterine Cervical Neoplasms
Study type: Interventional
Phase: Phase 4

Summary: 
      The purposes of this study are to evaluate the effectiveness of vaccination in 25-year old
      women at the time of their first access to cervical cancer screening, to understand the
      impact of vaccination on screening activity; to evaluate the immune response following
      vaccination; to study the dynamics of the infection after vaccination, including the possible
      change in the frequency of non-vaccine HPV types, to evaluate cytological abnormalities
      reductions in vaccinated women and to assess if HPV test in urine sample could be a useful
      non-invasive method to monitor HPV status in younger women.
    

Detailed description: 
      The present trial, funded by Istituto Toscano Tumori, started in 2010 and was directed to all
      women aged 25 (birth cohorts 1985 and 1986), resident in the province of Florence and
      targeted by the screening program. After receiving approval from the Ethics Committee of the
      Local Health Unit of Florence, women were invited by invitation letter containing a clear
      description of the study. All women complying with the invitation were asked to fill in the
      informed consent document.

      Women were randomized 1:2 in the Experimental Arm or in the Control Arm. At enrollment, women
      in the Experimental Arm, after collection of cervical samples (for Pap-test and HPV test),
      blood sample (for HPV antibody testing on serum before vaccination) and one first void urine
      sample (for HPV testing), received free vaccination with Cervarix® (vaccine against HPV 16
      and 18, 3 doses scheduled). Women in the Control Arm received usual care, i.e. the collection
      of cervical sample for Pap test.

      All women who signed the informed consent have been enrolled regardless of being sexually
      active or not. For virgo women cervical sample was not collected.

      At the second round of screening (30 months since enrollment), women in both Arms were asked
      to collect cervical samples (for Pap-test and HPV test) while a new blood sample for HPV
      antibody testing was collected only in women enrolled in the Experimental Arm.

      Women with normal cytology in Control Arm and women with HPV-negative result and normal
      cytology in Experimental Arm, received a recommendation by mail to repeat screening test
      after 3 years. Women with abnormal Pap test (Atypical Squamous Cells of Undetermined
      Significance or more severe, ASC-US+) were referred to immediate colposcopy at the Cancer
      Prevention and Research Insitute. Women with normal cytology and HPV positive were called
      after one year to repeat HPV test and Pap test. If HPV and Pap test were negative, women
      repeated both test after 30 months from enrolment. Otherwise if HPV test remained positive
      and/or cytology abnormalities were detected women were referred for colposcopy: if colposcopy
      didn't reveal high grade lesions (≤ CIN2) women repeated HPV and Pap test after 30 months
      from enrollment, if colposcopy revealed final histological diagnosis of CIN2+ lesions, women
      were recommended for an excisional treatment (both for study and control group).

      The presence of high risk (HR) HPVs was evaluated by Hybrid Capture 2 (Qiagen, Gaithersburg,
      USA) using probe B for the detection of 12 high risk HPV types: 16, 18, 31, 33, 35, 39, 45,
      51, 52, 56, 58, 59 (Group 1) and 1 "probably carcinogenic to humans" type HPV 68 (Group 2).

      HPV genotyping was performed by INNO-LiPA Genotyping Extra that allows the identification of
      28 different HPV types on L1 region on the HPV genome, it identifies all known HPV high-risk
      types (Group 1) 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59; "probably carcinogenic to
      humans" (Group 2A) HPV68; and all "possibly carcinogenic" HPV 26, 53, 66, 69, 70, 73, 82
      (Group 2B) and "not classified as to its carcinogenicity to humans" (Group 3) (6, 11); and
      other HPV types: 40, 43, 44, 54, 71, 74.

      HPV antibody testing was performed on an established and validated HPV serology method based
      on Luminex technology heparin coating of the beads and pseudovirions (PsVs) of 17 HPV types
      belonging to alpha species: 3, 6, 11, 16, 18, 31, 32 ,33, 35, 39, 45, 52, 56, 58, 59, 68, 73,
      and for four HPV types belonging to beta species: 5, 15, 38, 76.
    

Intervention name(s): Cervarix®, GlaxoSmithKline
Intervention type(s): Biological
Intervention description(s): 3 doses (0,1,6 months) of Cervarix®, GlaxoSmithKline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: cervical cancer screening; young women vaccination; impact of HPV vaccination on screening