Clinical trial NCT04910802: Concomitant HPV Vaccination and HPV Screening HPV Infection and Cervical Cancer in Sweden
Official title: Concomitant HPV Vaccination and HPV Screening for Rapid Elimination of HPV Infection and Cervical Cancer in Sweden
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: HPV Infection
CIN 2/3
Cervical Cancer
Lead sponsor: Region Stockholm
Sponsor class: OTHER_GOV
Collaborators: name: Karolinska University Hospital
First posted: 2021-06-02
Enrollment: 150000
Sex: FEMALE
Minimum age (years): 22
Maximum age (years): 27
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All women in the targeted age-range will be offered vaccination in conjunction with screening.
Primary purpose: PREVENTION

Brief summary: The study aims to evaluate whether organised, concomitant HPV vaccination and HPV screening offered to all resident women aged 22-27 will result in a more rapid elimination of HPV infection in Sweden. This objective will be examined at the population level.

Detailed description: In Sweden, 150 women die of and 550 women are diagnosed with cervical cancer each year. The average age at diagnosis is about 55 years and every third woman is under 40 years of age. World-wide, there half a million new cases of cervical cancer each year. The underlying cause of cervical cancer is a human papillomavirus (HPV), an infection that can be prevented by vaccination. The first-generation vaccine protects against HPV infection of the two types (16 and 18) that cause to about 70% of all cervical cancer. Since 2015, a second-generation vaccine (Gardasil 9, Sanofi Pasteur MSD SNC) has been available that provides protection against 9 HPV types of which 7 types (16, 18, 31, 33, 35, 45, 52 and 58) cause 90% of all cervical cancer.

In 2016, the World Health Organization (WHO) called on the countries of the world to eliminate cervical cancer as a public health problem. On 17 November 2020, all 194 WHO member states adopted a global strategy to increase the rate of elimination of cervical cancer. The strategy involves three main actions: vaccination, screening, and treatment. In Sweden, girls have been offered school-based vaccination against HPV with Gardasil 4 since 2012. Starting in the autumn of 2020, schoolboys have also been offered vaccination. Since 2019, the second-generation vaccine has been used in the school-based vaccination program. Sweden's vaccination strategy means that the virus will be eliminated among individuals born in 2007 and beyond. It will thus take another 20 years before Sweden can stop the infection in Sweden. Today, the infection continues to spread only among young adults. Studies have shown that vaccination up to age 26 can be effective and within the European Union, 10 out of 29 countries have a so-called catch-up on vaccination program targeting women over the age of 20 but such a catch-up has not been formally introduced in Sweden.

The overall goal is to investigate whether offering women ages 22-26 years vaccination with Gardasil 9 in connection with screening may involve a faster eradication of cervical cancer as a public health problem in Sweden. A regional pilot study will be conducted in 2021 followed by a subsequent scale-up to other regions.

Eligibility criteria: Inclusion Criteria:

* Eligible women will include resident women within the age range of 22-26, who have not opted out of the screening program and who consent to participate in the study.

Women who respond to the invitation and attend screening will be screened with HPV testing by the current routine practise. Women who consent to participate will also be offered HPV vaccination. The HPV vaccine (Gardasil 9) will be offered regardless of whether the woman reports having had prior vaccination with a first-generation vaccine (Gardasil 4) and regardless of screening test result.

Exclusion Criteria:

1. Known history of severe allergic reaction or hypersensitivity to any of the components of the HPV vaccine.For GARDASIL 9: Amorphous aluminium hydroxyphosphate sulphate adjuvant, Sodium chloride, L-histidine, Polysorbate 80 or Sodium borate
2. Known history of immune-related disorders
3. Current acute severe febrile illness, except for minor infections such as a cold, mild upper respiratory infection or low-grade fever.
4. Administration of immunoglobulin or blood-derived products within 6 months prior to scheduled HPV vaccine first dose
5. Current pregnancy (reported)
6. Women with a total hysterectomy

Primary outcomes:
measure: Prevalence of HPV
timeFrame: Measured at recruitment.
measure: Prevalence of HPV
timeFrame: Measured 3 years after recruitment, at the second cervical screening attendance.
measure: Prevalence of HPV
timeFrame: Measure 6 years after recruitment, at the third cervical screening attendance.
Secondary outcomes:
measure: Number of women with histopathologically confirmed cervical intraepithelial neoplasia grade 2, 3, or cervical cancer (CIN2+)
timeFrame: Measured at recruitment, and subsequently at 3 year intervals.
measure: Consumption of resources
timeFrame: Measured at recruitment, and subsequently at 3 year intervals.
measure: Number of women with obstetrical complications
timeFrame: Measured at recruitment, and subsequently at 3 year intervals.
measure: Number of women with cervical specimens found to be benign
timeFrame: Measured at recruitment, and subsequently at 3 year intervals.
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Cancer prevention, screening, and counseling unit, Regional Cancer Center of Stockholm-Gotland
Study officials:
affiliation: Karolinska University Hospital Laboratory
name: Joakim Dillner, MD, PhD
role: STUDY_DIRECTOR
References: