Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020. Rwanda is among countries with a high burden cervical cancer, with an annual incidence of 28.2/100,000 women (1,229 new cases in 2020) and a mortality rate of 20.1/100,000 (829 deaths in 2018) according to WHO (IARC 2020).

Cervical cancer is almost completely preventable because of the highly effective primary (HPV vaccine) and secondary (HPV screening) prevention measures. However, these measures have not been equitably implemented across and within LMICs countries.

Given the current situation, where the screening coverage is still low due to financial and operational challenges, it will take many years to achieve the elimination targets as included in the global elimination strategy. We are proposing to implement an innovative strategy to accelerate the elimination of cervical cancer in Rwanda consisting of concomitant HPV vaccination and HPV screening for young women aged 23-29 years old.

HPV screening and vaccination are complementary preventive options often implemented as separate public health programs. This project proposal aims to address this disconnect by combining both strategies with the ultimate purpose of accelerating the reduction of cervical cancer incidence and mortality in Rwanda and making the programs both cost-effective and sustainable.

Primary objective

The study aims to evaluate whether organized, concomitant HPV vaccination and HPV screening offered to girls and women aged 23-29 years will result in more rapid elimination of HPV infections in the target districts in Rwanda.

The study design is a before-after study design of the intervention, where the projected incidences and prevalence at the 2-year follow-up visit are modeled using the data from the baseline visit, with evaluation using Observed/expected numbers.

Secondary objectives

The study will evaluate whether concomitant vaccination and cervical screening result in an improved efficiency and/or safety of the cervical cancer screening program. These objectives will be examined among women who participated in the combined screening and vaccination study.

i) Protection of Gardasil 9 against HPV infection and against CIN2+ by Gardasil 9 HPV vaccine types in 23 to 29-year-old women from the study districts. This analysis will be performed every 2 years, and the first analysis will determine the effectiveness of one-dose vaccination (incident infections of HPV vaccine types at 2 years), whereas all subsequent analysis will determine the effect of 2-dose vaccinations. The study will be powered to detect a decline in invasive cervical cancer among the study participants, using the cervical cancer incidence in the surrounding districts of Rwanda as the reference.

ii) Efficiency will also be measured by the yield of histopathologically confirmed high-grade cervical cancer precursors or cancer (cervical intraepithelial neoplasia grade 2, 3, or cervical cancer) in relation to the consumption of resources and convenience for the women, using the yield at the baseline visit (10% of women tested) as the comparator. The hypothesis is that 2 years after vaccination, there will be only a few incident infections (only some old, persistent infections) resulting in high PPV and high yield of CIN2+ at modest consumption of resources.

End of the study

One screening interval (2 years) after the last visit of the last subject, defined as the day the last study subject receives her second vaccination.

The study will be implemented in 4 districts of Rwanda covering 100,000 women aged 23 to 29 years old. We will use Gardasil 9, the HPV the second generation HPV Vaccine manufactured by Merck.

Inclusion Criteria:

Eligible women will include women within the age range of 23-29, who have not opted out of the screening program and who consent to participate in the study

Exclusion Criteria:

• 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)
• Known history of immune-related disorders
• Current acute severe febrile illness, except for minor infections such as a cold, mild upper respiratory infection, or low-grade fever.
• Administration of immunoglobulin or blood-derived products within 6 months prior to the scheduled HPV vaccine first dose
• Current pregnancy (reported)
• Women with a total hysterectomy

Females are the only ones concerned by Cervical cancer

We plan to share aggregated results. The IPD will not be shared and this is in line with Rwanda National Ethics Committee and GCP principles