In pre-pandemic 2019, cancers were second to cardiovascular disease as the leading cause of global disease burden. Cervical cancer, a vaccine preventable disease, is in the top 5 causes of cancer cases and deaths among women globally!
Almost all cases of cervical cancer in women are caused by the Human papilloma virus (HPV). HPV is a double stranded DNA virus that belongs to the papilloma virus family and preferentially infects skin and mucosal cells. The virus is transmitted via skin to skin or mucosal contact. The virus is made up of two capsid proteins (L1 and L2) and 6 non-structural proteins that are involved in replication, making viral proteins, transforming cells into cancer cells and evading immune clearance.
There are over 200 types of HPV, many of them are low-risk types that cause no disease or warts in the mouth, throat, anus or genitals. There are 14 high risk types that cause HPV related cancers such as cervical cancer, anal, penile, vaginal, vulva and oropharyngeal cancers. The 14 types are HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. HPV infections are among the most common sexually transmitted infections. Most infections are asymptomatic, short lived and effectively cleared by the immune system within a few months. In some individuals, benign warts on the skin or genital regions can occur. In cases where the infection is due to high-risk cancer-causing types, the HPV genome may integrate into the human genome. This alone is not enough to cause cancer and other changes in the cell are necessary. Risk factors for developing cancer include infection with multiple HPV types, tobacco use, age, and immunosuppression including HIV infection. Good T cell immune function is necessary for clearance of HPV infection and its absence (e.g., in HIV infection) increases the risk of persistent infection and cancer.
In the 1970s Dr Harald zur Hausen working in Heidelberg, Germany proposed that a virus could cause cancer. He struggled to get this idea accepted until in 1983 when his team showed that HPV16 could be cloned from cervical cancer biopsies. This discovery led to a shift in the recognition of the role of viruses in causing cancer. His work also led to the development of diagnostic tests and vaccines for HPV. In 2008 he was awarded the Nobel Prize in Medicine “for his discovery of human papilloma viruses causing cervical cancer” (his co-awardees that year were Francoise Barre-Sinoussi and Luc Montagnier “for their discovery of human immunodeficiency virus”).
In 2020, the WHO launched the Global Strategy to Accelerate the Elimination of Cervical Cancer with a goal of reducing the incidence rate to 4/100,000 women globally and vaccinating 90% of girls by age 15 years by 2030. The WHO recommended that countries should include the HPV vaccine in national immunization programs. Females aged 9-14 years should receive the two-dose schedule (0, 6 months), those ages ≥15 years or immunocompromised (e.g., HIV infection) should receive the 3-dose schedule (0, 2, 6). However as of mid-2021 according to UNICEF, only 131 of 195 countries and territories had included HPV vaccines in their national immunization strategy. Africa has some of the highest incidence rates of cervical cancer in the world ranging from 6-40/100,000 depending on the region. As of June 2020, only 31% of African countries had introduced HPV vaccination [1].
There are currently 4 vaccines that have been prequalified by the WHO for protecting against HPV types that cause the majority of cervical cancers. The vaccines are highly effective (>95%) at preventing persistent infections and high-grade precancerous lesions and invasive cancers. Programs in most low- and middle-income countries are focused on vaccinating girls either through school based, community based, or health-facility based programs. Vaccination is most effective when administered prior to exposure and is therefore targeted to girls prior to onset of sexual activity at ages 9-14 years but can be extended to girls above age 15 years. Vaccination works; recent data suggests that even single dose coverage may provide good protective efficacy.
Screening guidelines may vary across countries but in general women above the age of 25 years if HIV infected and above age 30 years if HIV negative should undergo screening for HPV infection with an HPV specific test such as HPV DNA test. The screening tests should be repeated every 5 years in HIV negative women and more frequently (every 3-5 years) in HIV infected women with appropriate linkages for diagnostic verification and management of those that test positive.
Despite the ambitious vaccination goals, global HPV vaccination coverage rates remain low . The United States has some of the highest coverage rates with at least first dose coverage rates of 75.1% and full coverage of 58.6% (CDC, 2020). Coverage rates in the Africa region in 2021 were 26% for first dose and 18% for full coverage, closely resembling global coverage rates of 20% for first dose and 15% for last dose (WHO 2021). These coverage rates fall well below the WHO goal of 90% coverage by 2030. Significant efforts need to be made to improve vaccine uptake globally by scaling up vaccine manufacturing to meet global demand, improving access through vaccination campaigns and addressing vaccine hesitancy. The COVID-19 pandemic has led to school closures and closures of healthcare facilities during lockdowns. Many studies show significant disruptions in childhood immunization and school-based vaccination programs such as the HPV vaccination program. Some countries with long standing programs have reported reductions in vaccine uptake and low programmatic uptake over several years due to programmatic barriers, national health priorities as well as individual factors that drive parental consent and uptake.
As we strive for cancer moon-shots, let us remember that we already have a highly effective tool for preventing one of the deadliest cancers in women. Let’s collectively work together to effectively deploy this important tool. Cervical cancer is a vaccine preventable cancer that simply needs us to roll up our sleeves, make appropriate investments in manufacturing, distribution and communication so that we can vaccinate all adolescent girls. Rising cases of other vaccine preventable diseases such as measles and polio are evidence of worsening vaccine coverage due to access, hesitancy and COVID-19 related disruptions to preventative healthcare. HPV, however, will not show up tomorrow in the same way that measles does. Lapses in vaccination over the last couple of years will take decades to reveal themselves.
Not enough people associate HPV infection with the development of cervical cancer. Knowledge will be a powerful tool in promoting HPV vaccine acceptance. Peer to peer sharing of knowledge and practice has been shown to be highly effective in influencing parents and individuals within a community to vaccinate their children. If you are a parent vaccinate your children. If you are a girl or woman know and share your vaccination status with friends and family. If you are a woman above the age that is eligible for vaccination, make sure that you get screened and access care for positive results. If you are a healthcare worker educate both men and women about HPV and encourage vaccination and screening for women and girls. Together as communities supported by adequate public health resourcing, we can achieve the WHO goals of reducing cancer incidence and enhancing screening and treatment for cervical cancer among women before the end of this decade.
P.S. Although we have focused on HPV related cancers in women, the virus also causes infections and cancers in men including anal cancer, penile cancers and head and neck cancers. Preventing infections in boys is important in preventing cervical cancer. High income and upper-middle income countries provide vaccination for both boys and girls. The focus for most LMICs is currently on women and girls.
1. Bruni L, Saura-Lazaro A, Montoliu A, et al. HPV vaccination introduction worldwide and WHO and UNICEF estimates of national HPV immunization coverage 2010-2019. Prev Med 2021;144:106399. DOI: 10.1016/j.ypmed.2020.106399.
*A. Tariro Makadzange is the author of this blog. She is an infectious disease physician and viral immunologist focused on tackling healthcare programs in Africa.
*Nyasha Elose contributed editorial assistance.