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 anal 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, of which at least 13 are considered cancer causing. Anal and cervical cancers share some of these cancer-causing HPV types. Importantly, HPV types 16 and 18 likely cause 79% of anal cancers.

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, many HPV types have a tendency to infect the skin, causing skin warts on the hand and feet. Other HPV types, such as 6, 11, 16, and 18, specifically target mucus membranes and skin in genital areas including the penis, scrotum, anal canal, perianal regions, the vaginal entrance, vulva, and cervix. These types are primarily transmitted by genital contact. HPV types 6 and 11 can lead to genital warts while HPV types 16 and 18 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 anal cancer.

Anal Cancer

Anal cancer occurs in the anal canal, a short tube at the end of the rectum through which stool leaves the body. HPV infection is thought to cause up to 91% of anal cancers. The anal and cervical canals share an embryologic origin, and as such, anal epithelial cells respond similarly to HPV infection – the virus causes changes in cellular morphology and function of the host, ultimately leading to rapid cell proliferation and malignancy. Pre-cancerous cellular changes are classified as either low-grade or high-grade squamous intraepithelial lesions (“LSIL” or “HSIL”). HSILs have undergone more malignant changes and have a higher rate of progression to anal cancer.

Prevalence

Anal cancer represents about 1% of all new cancer cases in the U.S. and global incidence has been on the rise for the past 30 years. In the U.S., the American Cancer Society estimates that there will be over 8,000 new cases in 2016.

The signs and symptoms of anal cancer are variable and can include pain or pressure in the anus or rectum, a change in bowel habits, a lump near the anus, rectal bleeding, itching or discharge. Given the non-specific nature of these symptoms, screening is crucial to prevent the progression from infection to anal cancer, especially in patients considered high risk.

Those at greater risk for anal cancer include HIV-positive men and women, men who have sex with men (“MSM”), women with a history of high-grade cervical, vulvar, or vaginal dysplasia or cancer, and individuals with a history of anal warts.

Standard of Care

Similar to cervical cancer screening, the goal of anal cancer screening is to identify individuals with abnormal anal epithelial cells that could become cancerous. An anal Pap smear, alternatively called anal cytology, is the first step in screening. The procedure involves a cotton swab of the anal canal to collect cell samples, which are later viewed under the microscope. If abnormal cytology is present, patients undergo high-resolution anoscopy, a procedure that allows visualization and biopsy of the atypical lesion. At this point, the lesion can be diagnosed and graded according to severity of observed changes and an appropriate treatment course can be initiated. To date, no formal screening guidelines exist for anal cancer and its pre-cancerous forms.

Initial treatment generally involves combined chemotherapy and radiation. One seminal study reported local treatment failure in 36% of patients after three years of follow up. If initial treatments do not work, patients may require surgical removal of the anus, rectum, and part of the sigmoid colon. Quality of life for many anal cancer patients rests on the avoidance of colostomy, a procedure where a piece of healthy colon is diverted through a hole in the abdominal wall to create an alternative route for fecal waste. Colostomy is inevitable with surgical intervention and may also be a consequence of radiation toxicity or tumor location and size. In fact, up to one-third of patients may require a colostomy after curative-intent chemoradiotherapy. Additionally, pelvic radiotherapy is known to alter bowel, urinary, and sexual function in some cases, particularly in HIV-positive patients.

Opportunity

Despite available treatment, researchers predict that 1,080 patients will die of anal cancer in the U.S. in 2016. This translates to 13% of all new cases. The significant morbidity and mortality associated with anal cancer and its treatment calls for a substantial improvement in the current treatment paradigm.

Currently, prophylactic vaccination for anal cancer meets the same barriers seen in cervical cancer prevention – poor population coverage and lack of protection in infected individuals. At any given time, over 40% of HIV-negative MSM ages 16 to 26 will be infected with HPV in the anal canal. Prevalence jumps to nearly 100% in HIV-positive MSM. Considering the high rates of conversion to HSIL and low vaccination rates, there is an extremely vulnerable population that would benefit from HPV treatment rather than primary prevention.

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