The WHO has recently announced its commitment to end cervical cancer as a public health problem globally. Cervical cancer is the commonest cancer among women aged between 15 and 44 years in East Africa and is the leading cause of cancer-related mortality. It is caused by infection with human papillomavirus (HPV), a sexually transmitted virus. Infection with HPV can also cause other diseases such as genital warts, which affect both men and women. In high income countries, cervical cancer is prevented by vaccinating girls against HPV infection before they start having sex and screening sexually active women for HPV infection and/or cervical abnormalities. However, in many countries in Africa and other parts of the world, many women still die of the disease because screening programmes are absent or limited, and vaccination is only just starting to be rolled out. In Tanzania, which has one of the highest rates of cervical cancer in the world, HPV vaccines were introduced to 14-year-old girls in 2018. Evidence suggests that setting up and sustaining an HPV vaccination programme for young girls requires considerable investment in human and financial resources. These new programmes are finding it challenging to deliver the vaccines to most girls who should be receiving them. This will make it difficult to eliminate cervical cancer as HPV will still be able to spread in young people. Scientists therefore need to explore novel ways to deliver the vaccine to prevent infection to those who are not vaccinated. If enough people receive the HPV vaccine, then their unvaccinated sexual partners can also be protected. This has been shown in countries like Australia and Scotland, where vaccination of girls resulted in a decline in rates of HPV-related diseases in boys as well as girls. Given the challenges in getting enough girls vaccinated in many countries, one approach to controlling cervical cancer by preventing infection in unvaccinated girls is to offer the vaccine to their potential male sexual partners (known as gender-neutral vaccination). We propose to conduct a trial to test this strategy in Tanzania. We will see if we can reduce the amount of HPV infection present in communities by vaccinating of boys alongside vaccination of girls. We will do this using a single dose of HPV vaccine in boys, which may be sufficiently protective to prevent infection in boys and also prevent spread of HPV to unvaccinated girls. We will conduct a study called a cluster-randomised trial among communities in Tanzania (where each community is a cluster). In 2020, we will start by doing a baseline survey in 26 communities to determine how many boys and girls aged 16-22 years have HPV infection. We will then randomly select 13 communities where boys aged 14-18 years will be given HPV vaccine alongside the routine female HPV vaccination that is being given by the Tanzanian government. Three years after offering boys the vaccination, we will go back into the communities and do another survey to determine how many boys and girls aged 16-22 years-old have HPV infection. We will then be able to show whether the proportion of people infected with HPV differs between the communities that did and did not have male vaccination. At the same time, we will also be able to measure the impact of the girls-only vaccination on HPV infection by comparing the proportion of 16-22-year-old girls infected with HPV in the female-only vaccination communities at baseline and 3 years later. In our study, we will also follow up 200 vaccinated boys in order to check their immune responses to the vaccine, and we will do interviews in the communities to explore people's views about offering boys vaccination. We will also look at the cost of adding in vaccination of boys to the programme. This work will be extremely important in informing future HPV vaccination strategies and will be the first randomised trial of gender-neutral vaccination in Africa.