This year for International Women’s Day, the theme is ‘Inspire Inclusion’.

Encouraging women to stand up and be included in forging a better world.

In 2024, women and girls still have to fight to make informed decisions about their health and well-being. Although women and girls are constantly told to advocate for their health, they are not often given the resources, time, respect, or understanding to do this. Inclusivity in medical research is crucial to helping women make informed decisions.

This article details how research, including studies published in MDPI journals, is helping to bridge this gap and advocate for women’s inclusion. This includes bringing awareness to success in women’s health, such as cervical screening and prevention. As well as acknowledging the contributions made by important women such as Henrietta Lacks who changed the field of biomedical research and has helped to save countless lives.

Women’s inclusion in drug trials

It’s important to encourage advocacy of women’s healthcare given that, even in the modern day, there is still a sex bias in biomedical research. Furthermore, researchers primarily model and test most medications on male subjects. In many historical cases, males were considered less complex than females, whose menstrual cycle was deemed too difficult to factor into trials. It was suggested that the menstrual cycle contributed significantly to experimental variability which could negatively impact results. However, it has now been identified that the menstrual cycle typically doesn’t contribute to experimental variability. Moreover, it can be factored into certain experiments.

In the 1970s, women were excluded from participation in most clinical trials because of this reasoning. And historical exclusion has impacted inclusion and investment in women’s health.

Women have been misinformed about medication, including the dosage, which is predominantly based on a male’s anatomy. Because of this, women experience more side effects from medications at a higher rate than men.

Progress began to be made, however, once women’s inclusion in clinical trials was made law in 1993 by the National Institutes of Health (NIH).

Research regarding women’s inclusion in drug trials

A study conducted in 2010 confirmed that across 10 fields of biology, 80% of the animals used were male. A more recent follow-up study demonstrated that although there had been some increase in studies using both male and female subjects. There had been no change in the proportion of studies that included data analysed by sex. If both male and female models were tested and the data was analysed appropriately, the high rate of side effects could be avoided.

Additionally, prioritising women’s health would also mean more appropriate and accessible resources in health-related contexts that predominantly affect women. This includes menstruation, pregnancy, and certain types of cancer.

Cervical cancer

Cervical cancer is the fourth-most common cancer globally. It is also one of the top three cancers to affect women between the ages of 20 and 49. It primarily affects women and girls in low- and middle-income countries where prevention and treatment options are not as accessible. Furthermore, more than 85% of cervical cancer mortality occurs across 43 undeveloped nations. The mortality rate in these countries is 18 times greater than in developed countries.

The World Health Organisation (WHO) aims to eliminate the disease in the next century. In order to achieve this goal they must widen screening methods to include low-middle-income countries. In addition, open access is key to inclusivity to help educate and inform women and girls on cervical health.

The Human Papillomavirus (HPV)

The human papillomavirus virus (HPV) is the cause of 99.7% of cervical cancer cases. HPV is the most common sexually transmitted infection globally. There are over 100 different variations of the virus. HPV infection is common and is suggested to affect 80% of the sexually active women throughout a lifetime.

The immune system of healthy individuals who contract HPV can fight the infection and clear it within 1-2 years. Some HPV strains are low-risk strains, cause minor side effects, and can be treated easily. However, the high-risk strains have been linked to the development of cancers. This includes penis, vagina, and throat cancer, as well as cervical cancer.

HPV strains

Fourteen strains of HPV are associated with the development of cervical cancer; HPV 16 and HPV 18 account for most cases. However, even these strains can be cleared naturally by the immune system without causing further infection or disease. But problems can arise when HPV evades the immune response, resulting in persistent infection and the production of cervical lesions. This results in the stimulation and production of pro-inflammatory cytokines. This can cause the immune system to go into overdrive, attacking healthy cells, resulting in the development of cervical cancer. In addition, the presence of these cervical lesions increases the risk of developing cervical cancer.

History of Cervical Cancer Research

The developments in the field of prevention and treatment of cervical cancer could not have been possible without Henrietta Lacks.

Henrietta Lacks was a young mother of five; in 1951, she was diagnosed with a large malignant cervical tumour. A sample of her cancerous cells was sent to the lab for further examination. They discovered that Henrietta cells were unique from other cells taken from other cervical cancer patients in the past; they were labelled immortal as they could survive and reproduce outside of the body.

Henrietta’s cells changed not only research in the field of cervical cancer but the whole area of biomedical research. They are now referred to as HeLa cells and are used in multiple fields of research, where they have paved the way for many scientific breakthroughs in medicine.

For example, they are commonly used in the fields of cancer, immunology, and infectious diseases. In fact, the vaccine for COVID-19 was developed using HeLa cells. Despite HeLa cells becoming such an impactful tool in biomedical research, Henrietta and her family have not always received the credit they deserve. This International Women’s Day, we appreciate her donation to science by showcasing all the strides that have been made in cervical cancer research. Henrietta’s story demonstrates how female inclusivity in healthcare can impact change and development in the biomedical research field.

HeLa cells paved the way for cervical cancer prevention.

In 1985, scientists used HeLa cells to investigate cervical cancer. This involved isolating HPV from Henrietta’s cancerous cells and investigating how HPV was linked to cervical cancer. Furthermore, this work led to the development of the HPV vaccine as well as the development of the HPV test in screening programmes, and in 2008, one of the scientists, Dr. Harald zur Hausen, won a Nobel prize.

Cervical cancer prevention and screening

In recent years, the prevention and screening of cervical cancer have had breakthrough developments. This includes the development of the HPV vaccine, a screening programme, and follow-up treatment options. So much progress has been made in cervical research that the World Health Organisation aims to eliminate the disease in the next century.

History of cervical screening

The original method of cervical screening was founded by George Papanicolaou. Because of this, the test was named the Papanicolaou smear after its inventor. The whole process was a family contribution. In the early days of his research, George’s wife, Mary Papanicolaou, donated her vaginal smears for up to 20 years. Eventually, Mary Papanicolaou asked friends to volunteer, and because of this, George first identified cancerous cervical cells in a human. Even then, the screening had the power to be very successful in detecting early changes in the cervix. The cervical screening program would not be as successful as it is today without female inclusivity and participation. In addition, without the involvement of Mary and other female participants cervical screening would have taken longer to develop, endangering more lives.

Cervical screening today

The screening and testing process has had many improvements in recent years. For example, originally samples were collected from the cervix and then spread directly onto a slide. This early method caused many false-negatives and inconsistencies in the testing process. Because of this, liquid cytology methods were introduced in the early 2000s. Samples are now collected via brush and then deposited into a liquid buffer. This ensures all cells are collected and decreases the risk of cellular damage during the testing process. In addition, in the mid-2000s, another screening test, the HPV test, was added to the process.

HPV test

The sample is still collected using the same methods; however, the sample is now initially tested for the presence of infection with high-risk HPVs such as HPV-16 and HPV-18. If a positive result is detected, the sample is tested using a pap smear to identify carcinogenic changes in the cervix.

However, if this test shows no abnormal changes, the patient will be asked to attend another screening a year later to see if the body has cleared the infection. This method of detection can prevent the development of 93% of cervical cancers when paired with the HPV vaccine.

A recent Healthcare review discusses cervical cancer. In addition, it also discusses a new approach to cervical screening; dual-stain testing. This type of testing can be used to identify key biomarkers related to the development of HPV-16 and rapid cell division seen in pre-cancers and cancers.

Dual-staining can be used for patients who test HPV positive. The test is more specific and therefore, it’s a better detector for pre-cancerous and cancerous changes in the cervix. The review also highlights the advantage of new self-sample kits, which allow the patient to take their cervical sample. This approach can improve inclusivity and encourage more new patients to undergo screening, even if they would typically avoid an in-person appointment

HPV Vaccine

The HPV vaccine was first introduced and recommended in 2006, it was suggested to have the potential to prevent more that 90% of HPV-attributable cancers.The Centres for Disease Control and Prevention (CDC) originally recommended vaccinating girls aged 11–12, but they also indicated it could be given to 9-year-old girls. Now, the new vaccine is encouraged for females 9–26 years old. In addition, there are now six licenced vaccines available that prevent HPV infection and are used globally. Widening the age range for the vaccine means that girls and women who opted out from receiving the vaccine when it was first introduced have the option to reconsider. Women and girls are now able to make informed decisions about their health, based on positive data we now have access to regarding the vaccine.

HPV vaccine formulation

HPVs belong to the family Papillomaviridae and the subfamily Firstpapillomavirinae. There are two main structural proteins in HPVs, known as L1 and L2. L1 can spontaneously arrange into virus-like particles (VLPs), invoking an immune response. Researchers often use proteins with VLP properties in vaccines. This is because they can mimic specific viruses but cannot spread the viruses as they lack the virus’s DNA. This allows the immune system to create antibodies against the virus without causing any damaging effects or major symptoms of the disease.

The success of the vaccine

A review published in Diagnostics in 2023 discussed the success of the HPV vaccine by evaluating studies concerning the HPV vaccine. An example of this was a meta-analysis study that collected data from 65 studies and 14 countries on the effectiveness of the HPV vaccine on HPV-16/HPV-18 infection, anogenital warts, and high-grade CIN. It identified that there were significant reductions in infection via HPV-16 and HPV-18 in girls aged 13–24.

Furthermore, girls aged 13–19 experienced an 83% reduction in these strains, while those aged 20–24 saw a 66% reduction. The review acknowledged that this is a huge breakthrough in the prevention of cervical cancer. Also that the circulation of the HPV vaccine should be made more globally accessible to inspire inclusivity and reach the WHO goal of cervical cancer elimination.

Treatment

The screening programme has helped to improve the prognosis of cervical cancer. It does this by identifying pre-cancerous changes and lesions. Treatment of pre-cancers is usually quick and painless. Firstly, the precancerous lesions are located using a colonoscopy or visual inspection of the cervix. Treatment options can include thermal ablation, using a heated probe to burn off the precancerous cells, or cryotherapy, which uses a cold probe to freeze off the cells. Other treatment options include large loop excision of the transformation zone (LEETZ). This involves removing the precancerous cells using an electronically heated loop, and finally a cone biopsy. Early diagnosis of cervical cancer immediately improves the prognosis of the disease.

However, in some cases, for example those diagnosed in low-middle income countries, it may be too late for preventative treatments and early stage therapies. In such cases, healthcare providers should discuss other therapies. A review by Watkins and colleagues described contemporary treatments to cervical cancer, including Immune Checkpoint Inhibitors. Checkpoint inhibitors are a type of immunotherapy. They block proteins that stop the immune system from attacking the cancer cells.

Global Strategy to Eliminate Cervical Cancer

As mentioned above, the WHO have a goal to eliminate cervical cancer in the next decade. To achieve this goal the strategy must be extended to middle-low-income countries who do not have the same resources as other countries. The WHO have developed a strategy based on a mathematical model to achieve this goal.

The strategy mandates that 90% of girls receive full vaccination by the age of 15. Additionally, it requires 70% of women to undergo high-performance testing at the ages of 35 and 45. And finally, 90% of women identified with cervical disease should receive treatment (90% of women with precancer treated, and 90% of women with invasive cancer managed).

The mathematical model predicts that meeting this target should result in a 42% reduction in the median cervical cancer incidence rate by 2045 and a 97% reduction by 2120. Averting more than 74 million new cases of cervical cancer.

Furthermore, the median cumulative number of cervical cancer deaths averted will be 300 000 by 2030, over 14 million by 2070, and over 62 million by 2120.

Successes in global strategy

One strategy which is supporting the screening and treatment of women and girls in low-middle income countries is the ‘Scale-up Cervical Cancer Elimination with Secondary prevention Strategy’ project (SUCCESS). This project is a collaboration between Expertise France, Jhpiego, The Union for International Cancer Control (UICC) and Unitaid. The project targets women most at risk of cervical cancer in four low-middle-income countries including Côte d’Ivoire, Burkina Faso, the Philippines and Guatemala. These countries are representative of regions with limited resources where over 85% of women die from cervical cancer.

So far SUCCESS have screened 55,970 women and given 42,000 women HPV primary screening. In addition, they are investigating how to integrate HPV screening into existing health services. They also work closely with civil society organisations to develop national advocacy and community engagement strategies. This is to raise awareness and generate demand for cervical cancer services. In addition to regional engagement targeting 20 countries in Asia, Africa and Latin America.

Summary

Cervical cancer screening and prevention have had many important developments over the last 50 years. These updates have been so impactful that the WHO hopes to irradiate cervical cancer in the next century. The development of both the cervical screening programme and the vaccine would not have been possible without the contributions of brave women, including Henrietta Lacks and Mary Papanicolaou. This shows how important it is for women and girls to have information so that they can make informed decisions regarding their health.

In addition, resources regarding the screening programme, HPV vaccination, and treatment options need to be further developed. Moreover this will allow women and girls in low- and middle-income countries to become informed and give them the opportunity to make decisions about their health. As well as reaching the WHO goal of cervical cancer eradication.

If you enjoyed this article on women’s inclusion in healthcare, please see our other IWD content published this week including, What is the Gender Health Gap?

You can also view further articles which explore various aspects of Women’s Health here.