FASTER-Tlalpan Study in Mexico: HPV Vaccination Impact on Cervical Cancer Screening Program
FASTER-Tlalpan Study in Mexico: HPV Vaccination Impact on Cervical Cancer Screening Program
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.
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.
Inclusion Criteria:

 -  Female aged 25 to 45 years at the time of the first vaccine dose.

 -  Willing to comply with the requirements of the protocol (e.g., return for follow-up
 visits).

 -  Written informed consent prior to enrollment.

 Exclusion Criteria:

 -  Pregnant or breastfeeding. Women must be at least 3 months post-pregnancy and not
 breastfeeding to enter the study.

 -  Planning to become pregnant or planning to discontinue contraceptive precautions
 during the first twelve months of the study (months 0-12).

 -  History of allergic disease, suspected allergy or reactions likely to be exacerbated
 by any component of the vaccine.

 -  Any other medical condition or disease that could compromise the life of the
 participant during enrollment in the study.

 -  Use of any investigational or non-registered product (drug or vaccine) other than the
 study vaccines within 30 days prior to the first dose of the study vaccine.

 -  Previous vaccination against human papillomavirus.

 -  History of cervical cancer or hysterectomy.