FASTER-Tlalpan Study in Mexico: HPV Vaccination Impact on Cervical Cancer Screening Program
Condition: Cervical Intraepithelial Neoplasia; HPV-Related Cervical Carcinoma
MeSH terms: Uterine Cervical Dysplasia
Study type: Interventional
Phase: Phase 4

Summary: 
      Objective. To evaluate the impact of HPV vaccination as part of a hrHPV-based primary
      screening program to extend screening intervals.

      Materials and methods. A total of 3,000 women aged 25-45 years, attending the regular
      cervical cancer-screening program in primary health care services in Tlalpan, Mexico City,
      will be invited to the study. Eligible participants will be assigned to one of three
      comparison groups: 1) HPV16/18 vaccine and hrHPV-based screening; 2) HPV6/11/16/18 vaccine
      and hrHPV-based screening; 3) Control group who will receive only hrHPV-based screening.
      Strict surveillance of hrHPV persistent infection and occurrence of precancerous lesions will
      be conducted to estimate safety profiles at different screening intervals; participants will
      undergo diagnosis confirmation and treatment as necessary.

      Discussion: The FASTER-Tlalpan Study will provide insights into new approaches of cervical
      cancer prevention programs. It will offer valuable information on potential benefits of
      combining HPV vaccination and hrHPV-based screening to safety extend screening intervals.
    

Detailed description: 
      Cervical cancer mortality is a reflection of social inequity in health care. Globally,
      266,000 women die from cervical cancer annually, and 85% of these deaths occur in low- and
      middle income countries (LMIC).1,2 Persistent infection with high-risk human papillomavirus
      (hrHPV) is a necessary cause of cervical cancer.3,4 HPV16 and HPV18 are responsible for 70%
      of squamous cell carcinomas, and in conjunction with HPV45, cause 94.2% of cervical
      adenocarcinomas.4 The introduction of HPV vaccines will change the epidemiology of
      HPV-related cancers. However, it may take 30 years to observe the desired benefits of
      widespread vaccination when vaccinated cohorts reach the peak ages at which cervical cancer
      cases currently occur (e.g. women aged 40-50 years).5 As of August 2015, 84 countries and
      territories had national public-sector HPV immunization programs and 38 had pilot programs.6
      These programs mainly target adolescent girls to obtain the greatest cost-benefit ratio,7
      considering the initial price of the vaccine (>$100 US per dose).8,9 Women older than age 25
      are also vulnerable to new HPV infections10 and could also be vaccinated depending on
      country-specific resource availability.

      Recent results of Phase III HPV vaccination trials documented that the vaccine's efficacy
      among adult women is excellent (efficacy >80% to prevent resultant HPV-related cervical
      intraepithelial neoplasia).11,12 Additionally, current vaccines protect against both HPV16
      and HPV18 as well as provide cross-protection against other HPV types, particularly types 31
      and 45.13 Broad-spectrum protection such as this may lower the need for subsequent screening,
      warrant longer screening intervals than those currently used, and offer novel prevention
      policies against HPV-related cancers. The combination of vaccination and screening strategies
      to prevent cervical cancer may be particularly appropriate in countries with high incidence
      of cervical cancer that have already implemented hrHPV-based screening programs. These
      criteria are satisfied in Mexico.14 A broader age range of females in population-based HPV
      vaccination programs could have direct benefits for vaccinated females, and indirect benefits
      for non-vaccinated females and male sexual partners via increased herd immunity to reduce
      HPV-related cancers.15 Based on the high efficacy of the HPV vaccine in older women, a novel
      strategy combining vaccination and screening, HPV FASTER, has been proposed.16 In accordance
      with this proposal, HPV vaccination of women in a broad age range can offer protection to
      women who are not currently infected, but also can protect against subsequent re-infection.16
      As a result, a combined strategy of HPV vaccination and screening may reduce the lifetime
      number of screens used by the current hrHPV-based screening programs. If a screening and
      vaccination strategy is widely adopted, we expect promising results. This strategy has the
      potential to: 1) mitigate the screening demand on both women and health services by extending
      screening intervals; 2) improve the cost-benefit balance of screening programs; and 3)
      provide greater protection and quality of life to a large number of women through a reduction
      in cervical cancer.17 An intervention such as this may not only save many lives in the next
      30 years but also be cost-effective.

      However, the data on efficacy of HPV vaccination in older women to reduce cervical cancer
      risk, and not just the risk of precancerous lesions, are lacking. That is, there is currently
      insufficient knowledge regarding the role of HPV vaccination in older women to permit
      screening intervals to be extend safely following a negative screen (Figure 1).

      A significant challenge for HPV-vaccine uptake is the number of doses in the standard vaccine
      schedule. Although licensed in some countries for use among older individuals, national HPV
      vaccination programs target teenagers and young adults. Recent studies found that fewer than
      three doses of the two commercially available prophylactic HPV vaccines seem to provide
      similar protection against cervical HPV16 and HPV18 infections as the three-dose schedule in
      women younger than 25 years old. 18,19 Herein we propose a population-based study to assess
      the efficacy of a 2-dose HPV vaccination with [HPV16/18 AS04-adjuvanted vaccine (Cervarix ®)
      and HPV 6/11/16/18 vaccine (Gardasil®)] against HPV-persistent infection and HPV-related
      cervical disease in older women between 25 and 45 years of age attending clinics for
      hrHPV-based screening.
    

Intervention name(s): CERVARIX; GARDASIL
Intervention type(s): Biological; Biological
Intervention description(s): - HPV16/18 L1 VLP AS04 vaccine (Cervarix®) group according to a two-dose schedule (0-12 month). This group will receive the HPV16/18 vaccine containing HPV16 and HPV18 L1 virus-like-particles (20 μg of each) adjuvanted with 50 μg 3-O-desacyl-4'-monophosphoryl lipid A and 0.5 mg aluminum hydroxide (GlaxoSmithKline Biologicals, Rixensart, Belgium). A 0.5-mL dose of the vaccine will be administered in the non-dominant arm.; Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) (Gardasil®) recombinant vaccine according to a two dose schedule (0-12 month). This group will receive amorphous aluminum hydroxyphosphate sulfate adjuvanted quadrivalent HPV (types 6, 11, 16, 18) L1 VLP vaccine (Merck Sharp & Dohme Corp. Whitehouse Station, NJ, USA). A 0.5-mL dose of the vaccine will be administered in the non-dominant arm.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Health Services Research
Keywords: Mass screening; Vaccination; Mexico