Cervical cancer incidence declines as rates of other HPV-associated cancers rise
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Incidence of cervical cancer declined as rates of other HPV-associated cancers increased significantly in the U.S. from 2001 to 2017, according to a population-based study of trends presented during the virtual ASCO Annual Meeting.
“As a gynecologic oncologist, I knew about cervical, vulvar and vaginal cancer, but HPV can induce a lot of cancers, such as oropharyngeal, penile, anal and rectal cancers,” Cheng-I Liao, MD, attending physician at Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan, told Healio. “If we can figure out the status of HPV-associated cancer in the United States, we can understand the need of our patients and try to eliminate these diseases. The U.S. Cancer Statistics Public Use Databases had near-100% population of the U.S. We can use this to solve these problems.”
Liao and colleagues analyzed incidence and trends of HPV-associated cancers among 657,317 individuals (60% women) included in U.S. Cancer Statistics databases between 2001 and 2017, and sought to determine if screening or vaccinations had made a difference during that period. They stratified cancers by sex, race and age groups and calculated incidence trends per 100,000 using SEER*Stat and Joinpoint Trend Analysis software.
Results showed incidence of cervical carcinoma — which accounted for 52% of all HPV-associated cancers in women and for which, researchers noted, clear guidelines on screening and vaccination exist — decreased by about 1% annually (annual percent change [APC] = 1.03%; P < .05) between 2001 and 2017, to 7.12 cases per 100,000 in 2017.
Meanwhile, rates of HPV-related cancers without standardized screening guidelines increased among women, including oropharyngeal (APC = 0.77%), anal and rectal (APC = 2.75%), and vulvar (APC = 1.27%) cancers (P < .001 for all).
“It is likely that the significant decrease in cervical cancer incidence resulted from clear guidelines for cervical cancer screening and may also reflect promotion and acceptance of vaccination, particularly in younger women,” Liao said.
Researchers observed the sharpest decrease in cervical cancer incidence among women aged 20 to 24 years (APC = 4.63%; P < .001).
Among women aged older than 50 years, incidence of cervical cancer decreased by 1.53% per year, whereas incidence of anal and rectal cancer increased by 3.55% per year. Researchers projected that by 2025, rates of anal and rectal cancer would surpass those of cervical carcinoma among women in every age group over 50 years.
Among men, researchers reported an annual increase in HPV-associated cancers of 2.36% per year (P < .001), with a rate of 11 per 100,000 in 2017. Cancers with the highest increases among men included oropharyngeal (APC = 2.71%) and anal and rectal squamous cell carcinoma (APC = 1.71%). Oropharyngeal squamous cell carcinoma accounted for over 80% of HPV-associated cancers in men, a fivefold higher incidence compared with women (age-adjusted incidence per 100,000, 8.89 vs. 1.68).
The HPV vaccine received approval in 2006 for girls and women aged 9 to 26 years to prevent HPV infection and the development of cervical cancer lesions. Updated recommendations in 2011 extended vaccination to boys aged 11 to 12 years. Vaccination currently is recommended for individuals up to age 45 years.
Liao and colleagues called for more resources and research to address the lack of screening and vaccination recommendations in the other preventable HPV-related cancers.
“In order to reduce these trends and achieve success comparable to what we’re seeing with cervical cancer, we must develop effective screening strategies and determine vaccine efficacy in these patient populations,” Liao said.
Perspective
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Marcia Amelia Ciccone, MD
Liao and colleagues presented interesting data on the change in incidence rates of HPV-related cancers over time, projecting that the rates of anal and rectal cancer in women would exceed cervical cancer by 2025. This seems partially due to improvements in screening for cervical cancer and, in the younger cohort, due to vaccine prevention of HPV infection. Increases in anal and rectal cancer may be due to increasing HPV incidence in the unvaccinated, older population, increased detection, and lack of clear screening protocols.
Of course, that projection is dependent on the rates continuing at their current pace, which may be affected by the HPV vaccine and when the cohort of those who have been vaccinated become older. Currently, those who are vaccinated comprise a younger cohort than those who are typically getting cancer.
The researchers also noted an overall increase, by about 2.36% per year, in the incidence of HPV-related carcinomas among men. In general, we know HPV-related cancers also occur in men, but the focus has been on cervical cancer in women. This is an important finding because, in terms of protection and detection, we don’t have a screening test for men, and we’ve been behind on promoting HPV vaccination for them. Men cannot only get these cancers, but they can spread HPV to women, too. It’s just as important for men to be vaccinated as women.
Although Liao and colleagues reported that 80% of all HPV-associated cancers among men were oropharyngeal cancers, it’s important to recognize that data within the SEER database do not account for whether every individual case is HPV-related. With cervical cancer, for example, almost 100% are HPV-related. In anal cancer, 90% are HPV-related and, in oropharyngeal cancers, 70% are HPV-related. The other 30% are not related to HPV and can be caused by smoking or chewing tobacco. If there are more cases occurring among men, is that because there are more men who are smoking or chewing tobacco than women? The degree of this effect should be explored, but likely won’t entirely account for the differences we’re seeing.
The causes and reasons behind these increases remain to be elucidated. Are these specifically HPV-related cancers that are increasing, meaning the actual incidence cases are related to HPV? What percentage are not?
The results also raise the questions of whether we should be doing more anal pap smears and looking into creating official screening guidelines so that anorectal precancers can be detected and treated.
Lastly, the research from Liao and colleagues makes me wonder if we’re doing enough for our younger population, in terms of getting people vaccinated and offering them catch-up vaccines now that the vaccine is approved for patients up to age 45 years. We need to focus on getting that vaccination to men, too, and on increasing public awareness. Getting word out to the general public and especially publicizing studies, such as this one, is extremely important. We have a cancer-preventing vaccine available! Our current vaccination uptake in the U.S. is only 50%. In my ideal world, everyone eligible would get one.
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Liao C-I, et al. Scheduled for presentation at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.
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