Assets and obstacles in the fight to prevent HPV-related cancers

Despite the availability of vaccines that could prevent the majority of cancers caused by the human papillomavirus (HPV), the incidence of cervical, oropharyngeal, anal, vulvar and vaginal cancers is increasing in the United States. 

MD Anderson’s HPV-Related Cancers Moon Shot™ is working to identify practical solutions and strategies to increase vaccination rates, improve screening and diagnostic options, and develop novel therapeutics to impact the incidence of and deaths caused by HPV-related malignancies. The moon shot is part of the Moon Shots Program™, a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patients’ lives.

Erich Sturgis, M.D., professor of Head and Neck Surgery, and Kathleen Schmeler, M.D., associate professor of Gynecologic Oncology and Reproductive Medicine, spoke with Cancer Frontline about comprehensive efforts to reduce the burden of HPV-related cancers in the U.S.

Q: Can you describe the problem we currently face in Texas and the U.S. with HPV-related cancers?

Sturgis: HPV-related cancers account for approximately 5% of cancers worldwide. The greatest burden of HPV-related cancers in women is cervical cancer. In men, it’s oropharyngeal cancer. Each year in the U.S., HPV-related cancers collectively account for approximately 50,000 new cases, more than 10,000 deaths, and over $1 billion in treatment costs. 

Since the mid-1990s, the U.S. has been experiencing an epidemic of oropharyngeal cancers in men. It is estimated that by 2020 there will be more cases of HPV-related oropharyngeal cancer in men than cervical cancer in women. 

However, in Texas, cervical cancer incidence is among the highest in the country, with some of the highest rates found along the Texas-Mexico border in the Rio Grande Valley (RGV). Women in the RGV have been shown to have 30% higher cervical cancer incidence and mortality rates compared with women living in non-border counties. 

Q: What options do we have to prevent or treat HPV-related cancers? What challenges do we face?

Schmeler: If diagnosed in a pre-cancerous or early stage, most HPV-related cancers are curable. However, screening tests are not available for some of these cancer types, and screening tests and/or guidelines and algorithms do not exist or are not accessible to high-risk populations. 

The most effective way to reduce HPV infection rates is through HPV immunization. Dr. Lois Ramondetta and her team have worked tirelessly to increase awareness and uptake of the vaccine. Prophylactic vaccines against HPV have been commercially available since 2006 and are very effective in preventing HPV infection and associated pre-cancers and cancers. Because the vaccines are most effective if given prior to HPV exposure, the CDC recommends that boys and girls complete the two-dose vaccine series before age 13. But they can be administered as early as age 9 and up to age 26. 

However, HPV vaccination rates in the U.S. are poor, with only 50% of girls and 38% of boys completing the vaccination series. HPV vaccination rates in Texas are particularly poor – only 40% of girls and 27% of boys complete the vaccination series. The state ranks 47th in the country in this respect. 

It’s also important to point out that existing vaccines have no effect on pre-existing HPV infections or related pre-cancers and cancers in people already exposed. That means there are two to three generations who will not benefit from the vaccine, as they were too old to receive the vaccine when it was made available. We therefore anticipate a continued need for the screening, diagnosis and treatment of HPV-related pre-cancers and cancers for the foreseeable future.  

Q: What must be done to make further progress toward eliminating HPV-related cancers?

Sturgis: Without screening, most HPV-related cancers are diagnosed at a late stage, requiring complicated care that often includes a combination of radiotherapy, chemotherapy and/or radical surgery. While these treatments can result in a cure if the cancer is found early enough, they are very expensive and many survivors suffer major long-term side effects and complications. When/if they have a cancer recurrence, most patients will die of uncontrolled cancer progression. 

Progress toward eliminating HPV-related cancers will require several things:

• The development of novel screening paradigms and guidelines for HPV-related cancers.
• Incorporation of innovative technologies for the screening and diagnosis of HPV-related cancers.
• Estimating the cost effectiveness of and budget impact of the above actions at a population level for the state of Texas.
• Improving access to care, including HPV vaccination.

Q: How do you hope to address those needs in the future?

Schmeler: Together with our collaborators, we have initiated a number of studies to develop and implement new methods for screening, diagnosis and treatment of HPV-related cancers and pre-cancers.

I am working with Dr. Rebecca Richards-Kortum, a Bioengineer from Rice University to develop new technologies and explore community outreach strategies to improve cervical cancer screening and diagnosis in resource-limited settings, such as the RGV. 

In the U.S., cervical cancer outreach efforts have focused mainly on increasing clinic-based Pap and HPV testing for primary cervical cancer screening, but data suggest that clinic-based screening may not be practical or feasible for some women due to a variety of socioeconomic, cultural and religious reasons. Allowing women to do self-sampling at home or at a community event, without having to travel to a clinic and undergo an exam, may improve screening rates in medically underserved regions. Also, offering a point-of-care diagnostic procedure, such as the high-resolution microendoscope (HRME), which is a novel imaging tool developed at Rice University, could be practice-changing by providing an immediate diagnosis of cervical and anal pre-cancer and cancer without having to perform a biopsy. If successful, patients would be able to avoid biopsies and undergo diagnosis and treatment in a single visit.

Dr. Sturgis and I also have worked to initiate several clinical studies at MD Anderson to identify promising screening approaches for non-cervical cancer types, including the anus and oropharynx. 

The PANDA (Prevalence of Anal Dysplasia And cancer) trial is using Pap and HPV testing, as well as high-resolution anoscopy, to screen for anal cancer in women who have an increased risk because of a history of HPV-related genital disease. The HOUSTON (HPV-related Oropharyngeal and Uncommon Cancers Screening Trial Of meN), aims to identify men at high-risk for developing HPV-related cancers through a biomarker assay and screen them for oropharyngeal, anal and penile cancers and pre-cancers. Both studies are supported by the moon shot.

To our knowledge, there currently are no trials ongoing to develop such a comprehensive screening strategy for these cancers.

Q: How have your collaborations across disease sites enabled you to begin working toward these goals?

Sturgis: Our HPV projects in the area of screening and diagnosis involve collaborations with nearly 30 investigators from 11 different institutions, nine of which are located in Texas. Approaching HPV-related diseases as a group, regardless of organ site, has allowed us to make great advances in our research. And working with collaborators from different backgrounds (surgery, medical oncology, gynecologic oncology, radiation oncology, epidemiology, public health, bioengineering and cost-effectiveness) has allowed us to have a greater impact in fighting HPV-related cancers.