We have the opportunity to prevent the majority of anal cancers, we just need to make it [HPV vaccination] a national and global public health commitment.— Felix A. Mensah, MD
The incidence rate of human papillomavirus (HPV)-related anal cancer and its precursor lesion, anal intraepithelial neoplasia, is rising in the United States and globally. Although 5-year survival rates in localized disease are generally favorable, survival in metastatic disease remains poor, leading to the conclusion that prevention may be the optimal approach for reducing the disease burden. To shed light on this generally underreported clinical issue, The ASCO Post spoke with Felix A. Mensah, MD, Fellow, Section of Hematology/Oncology, Georgia Regents University, Augusta. Dr. Mensah recently published a paper on the HPV vaccine and its role in preventing and treating anal cancer.
Interest in Geriatric Oncology
Please tell our readers a bit about your background and current position.
I was born and raised in Takoradi, a port city in Ghana. I did my training in internal medicine and pediatrics at St. Louis University in St. Louis, Missouri. During my residency, my interest in adult oncology grew tremendously, and after graduation, I worked as an internist in Springfield, Missouri, and then returned to St. Louis for my geriatric fellowship training. I’m currently a fellow in hematology/oncology at Georgia Regents University, Augusta.
Increasing Incidence of Anal Cancer
Briefly shed some light on the epidemiology of this disease.
Anal cancer is a fairly rare malignancy. In the United States, it makes up about only 2.5% of all gastrointestinal malignancies, with about 7,210 new cases diagnosed each year, and about 95% of these cases are diagnosed in patients 25 years or older, with a median age of 61 years.
Although it varies geographically, females have a slightly higher incidence rate than males. According to the SEER [Surveillance, Epidemiology, and End Results Program] database, rates for new cases of anal cancer have been rising on the average of 2.2% per year over the past decade, with death rates rising on the average of 1.7% over the same period.
It’s interesting to note that the overall incidence has increased three times (from 1.0 to 3.0 per 100,000 person-years) and 1.7 times in women (from 1.4 to 2.4 per 100,000 person-years) when data from 1973 through 1996 were compared with data from 1997 to 2009. Moreover, anal cancer rates were higher among white women, whereas in black people, the rate is higher in men.
There is a much higher incidence of anal cancer in high-risk populations, especially in men who have sex with men and in patients who are seropositive for HIV [human immunodeficiency virus]. Other high-risk groups compared with the general population include women who test positive for HIV, women with cervical or vulvar cancer, and people in chronic immunosuppressive states not due to HIV.
Anal Intercourse: A Contributing Factor
First, could you explain why there’s been an increase in the incidence of anal cancer and anal intraepithelial neoplasia.
We know that the major contributing factors for the increase in anal cancer incidence include increasing receptive anal intercourse in heterosexual and homosexual populations, increasing HPV infections, and longer life expectancy of treated people who are seropositive for HIV. But it is important to note that the perception that receptive anal intercourse is limited to male homosexual practices is quickly becoming outdated, as increasing global rates of heterosexual anal intercourse have been reported. For instance, women in the United States may be more likely to engage in unprotected anal intercourse than homosexual men.
When risk factors that contribute to the increase in this disease are assessed, it seems that participants in trials are often reluctant to report anal intercourse for fear of stigmatization. However, it is evident that heterosexual anal intercourse can no longer be ignored when it comes to HPV and anal cancer.
As a follow-up, does this knowledge of causative factors offer any clues that might help in prevention?
Currently, there are three licensed prophylactic HPV vaccines: the bivalent vaccine against HPV-16 and -18 (Cervarix), the quadrivalent vaccine against HPV types 6, 11, 16, and 18; and most recently Gardasil 9, which protects against the four strains approved in the previous Gardasil vaccine, as well as 31, 33, 45, 52, and 58.
The vaccines are made up of DNA-free, virus-like particles, both produced by expression of the major structural L1 gene of the HPV types.
However, unlike with cervical cancer, we have no standardized practices for routine screening for and treatment of anal cancer, which makes the need for a preventive vaccine even more imperative. Given that infection with high-risk HPV types is associated with an increased risk of developing dysplasia or cancer, prevention is especially important in patients who are seropositive for HIV and other high-risk groups; these patients are particularly susceptible to persistent HPV infection. The association of HPV with 91% of cases of anal cancer provides an excellent opportunity for prevention and treatment strategies.
Multimodal Treatment Approach Needed
As HPV-related anal cancer remains a difficult disease to treat, what are the current management approaches?
Currently, the treatment recommendation for HPV-related squamous cell carcinoma of the anus involves screening at-risk patients and observing precancerous lesions with the intention of early detection and eradication. Treatment options include laser ablation, surgical resection, and chemoradiation.
Successful eradication of lesions has been difficult, and recurrence is high, particularly among patients who are seropositive for HIV. The current cancer treatment consensus is that a multimodality treatment approach that combines immunotherapy with radiation and chemotherapy is clearly needed to have the best effect on tumor cell reduction and eradication.
Is there current work looking at the therapeutic possibility of a vaccine?
Yes, there is a rapidly evolving interest in the prospect of therapeutic vaccination in anal cancer. These vaccines are likely to be based on the platform of immunotherapy targeting E6 and E7 oncoproteins, including T-helper 1 and CD8+ T cells specific to the virus. The oncogenic pathophysiology of HPV-related anal squamous cell carcinoma makes this approach a reasonable one. Several early trials have shown promise, but there have been inconsistent clinical responses. So, I think we are heading in the right direction, but there is much work ahead.
Many More Hills to Climb
Would you like to share any closing thoughts?
We have made significant progress in this disease, but there are many more hills to climb. As the therapeutic route is still a long way off, we need to concentrate on primary and secondary prevention strategies. We also need to overcome cultural biases, which, as we’ve seen with vaccination phobia in the United States, are not limited to the developing world. Statistics on U.S. HPV vaccination rates among girls aged 13 years to 17 years in 2013 showed a rate of only about 37%; vaccination rates among U.S. boys in the same age group were only about 13%.1,2
However, other developed countries such as Australia and the UK have much higher rates of vaccination among girls. For instance, in Australia, about 73% of girls are vaccinated when they turn 15 years old; a vaccination program for boys aged 15 has recently been adopted, with a participation rate of about 60%. In the UK, about 86% of girls aged 12 to 13 are vaccinated; vaccination of boys in the UK is not covered under the universal health plan.3,4
Through low-cost vaccines, countries in sub-Saharan Africa are having success with vaccination. Rwanda, for instance, was able to achieve a 93% vaccination rate among girls.5 So, we have the opportunity to prevent the majority of anal cancers, we just need to make it a national and global public health commitment. ■
Disclosure: Dr. Mensah reported no potential conflicts of interest.
1. Centers for Disease Control and Prevention: 2011 Archived teen vaccination coverage. Available at http://www.cdc.gov/vaccines/who/teens/vac-coverage/vac-coverage-2011.html. Accessed May 12, 2014.
3. Brosi C, Bicknell L, Winch K, et al: Human papillomavirus control: How are we going with vaccination coverage seven years in? Poster presented at Communicable Disease Control Conference. June 1-2, 2015. Brisbane, Australia.
4. Public Health England: Human papillomavirus immunisation programme review: 2008 to 2014. Available at http://www.gov.uk/government/uploads/system/uploads/attachment_data/file/412264/HPVVaccine_Coverage_in_England_200809_to_201314. pdf. Accessed July 3, 2015.