About HPV

Human papillomavirus (“HPV”) is a group of viruses that is extremely common worldwide. Some types of HPV can cause health problems, ranging from benign issues like skin warts to life-threatening conditions including cervical cancer.

HPV is the most common sexually transmitted infection in the U.S. In fact, it is so common that nearly all sexually active men and women get it at some point in their lives. In the U.S., an estimated 79 million persons are currently infected with HPV and there are 14 million new infections each year. In the majority of cases, HPV infections clear spontaneously and most people never realize they were infected. However, some infections persist, cause symptoms, and reactivate years after initial exposure.

There are more than 150 types of HPV. At least 13 types of HPV are considered cancer causing and are known as “high-risk” HPV types. Effective prophylactic vaccines exist to prevent HPV infection in women and men, however there are no effective antivirals to treat those already infected.

HPV is spread through skin-to-skin contact and can cause normal cells on infected skin to turn abnormal. Different HPV types have a propensity to infect different body sites. For example, HPV types 6 and 11 have a tendency to infect the skin, causing skin warts on the hand and feet. Other HPV types, such as 16 and 18, specifically target mucus epithelium and can lead to abnormal cell proliferation and cancer.

Rendering of HPV type 16. HPV causes skin and genital warts and a number of cancers, including cervical cancer.

Cervical Cancer

Cervical cancer is a cancer arising from the cervix. HPV infection is involved in the development of the majority of cervical cancer cases.

The eight most common HPV types that contribute to invasive cervical cancer are 16, 18, 31, 33, 35, 45, 52, and 58 with a predominant role for types 16, 18, and 45. Over 70% of cervical cancers have been tied to the high risk HPV types 16 and 18.

These high-risk HPV types contain proteins that inhibit tumor suppressors in infected cells. The infected cells are therefore able to proliferate without inhibition, leading to tumor growth and malignancy. At the start of the progression to cancer, infected cervical cells start to display low-grade squamous intraepithelial lesions (“LSIL”) where the cervical cells appear mildly abnormal.

Over time, there is a progression to high-grade squamous intraepithelial lesions (“HSIL”). HSIL suggest more serious, precancerous changes in the cervix compared to LSIL. After initially contracting HPV, it often takes years, or even decades, to develop cervical cancer.

Healthy Cervix
Early-stage Cervical Cancer
Stage II Cervical Cancer

Prevalence

Worldwide, cervical cancer is the fourth most common cancer in women with an estimated 530,000 new cases each year. Cervical cancer causes more than 270,000 deaths annually, with nearly 85% of deaths occurring in developing countries.

In the U.S., cervical cancer was once one of the leading causes of cancer death for women, but with improved screening the number of deaths has decreased significantly. In 2013, nearly 12,000 women in the U.S. were diagnosed with cervical cancer of which 4,000 died. Cervical cancer affects women at a significantly younger age than most other malignancies. Between 2008 and 2012, 39% of new cases diagnosed in the U.S. were in women under the age of 45.

Standard of Care

Cervical cancer screening is used to find abnormal changes in the cells of the cervix that could lead to cancer. Screening includes an HPV test and a pap smear to assess if the patient has normal cervical cells, LSIL or HSIL. If the results are indicative of a possible cervical cancer, a physician will perform a colposcopic exam to biopsy the abnormal areas, determine if the abnormal cells are cancerous, and design a treatment plan.

Treatment of cervical cancer is dependent on the stage of disease. Cancers at earlier stages are treated surgically or through radiation. Surgical therapy involves either partial or complete removal of the uterus, lymph nodes, and surrounding affected organs. Advanced disease is treated with chemotherapy. Given the high prevalence of women diagnosed at childbearing ages, many women with early stage cancer hope to remain fertile following surgery. Many advances have been made to decrease morbidity, but some women suffer from blood loss, injury, sexual dysfunction, and infertility after treatment.

There are currently no therapies that provide HPV patients with a sustained immunologic response. Thus, primary prevention by vaccination to increase herd immunity remains the primary focus in controlling the spread of HPV infection. The CDC recommends vaccination of children between the age of 11 and 12.

To date, vaccination has proven effective in controlling the prevalence and incidence of HPV-related disease. In the U.S., the prevalence of HPV 6, 11, 16, and 18 in cervical samples from females aged 14 to 19 years decreased by 64% between 2006 and 2016 (from 11.5% to 4.3%).

Opportunity

Current prophylactic vaccines have no benefit to those already infected with HPV. In 2013, only about 40% of women aged 19 to 26 years reported receipt of at least one dose of the HPV vaccine and less than 7% of men in the same age group reported receiving any HPV vaccination.

Given that at any point in time, 10% of all healthy, unvaccinated women in the world will have active HPV infection there is a large market of individuals who are not protected by vaccination and either at risk of infection or already infected without their knowledge.

With the high rates of HPV in unvaccinated individuals, the low rates of HPV vaccination among young women, the limited coverage of widely used vaccines, and the invasive, potentially life-altering impacts of cervical cancer treatment, there is a market opportunity for therapies that directly attack the HPV virus when treating persons with cancerous lesions. Agenovir is developing novel therapies to combat latent HPV infections that may lead to cervical cancer.

Percent of Females Aged 13 – 17 Years Who Have Received One or More Doses of a HPV Vaccine (2015)

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