Epidemiology of HPV Cancers
1) How prevalent are genital HPV infections in the US among different racial and ethnic groups?Open or CloseAccording to the CDC:
During 2013–2014, prevalence of any genital HPV was 42.5% among adults aged 18–59, 45.2% among men and 39.9% among women.
Overall, and for both men and women, prevalence of any genital HPV was lowest among non-Hispanic Asian adults and highest among non-Hispanic black adults, with no significant difference in prevalence between non-Hispanic white and Hispanic adults.
Prevalence of any genital HPV was higher among men than women overall and among non-Hispanic white adults. The pattern was similar for Hispanic adults, but the difference between men and women was not statistically significant.
Prevalence of high-risk genital HPV was lowest among non-Hispanic Asian adults and highest among non-Hispanic black adults.
During 2013–2014, the prevalence of high-risk HPV was 22.7% among adults aged 18–59, 25.1% among men and 20.4% among women.
Overall, and for both men and women, prevalence of high-risk genital HPV was lowest among non-Hispanic Asian adults and highest among non-Hispanic black adults, with no significant difference in prevalence between non-Hispanic white and Hispanic adults.
Prevalence of any genital HPV was higher among men than women overall and among non-Hispanic white and non-Hispanic black adults.”
A more detailed look at racial disparities in occurrence of HPV-caused cancers and how the availability of the vaccine has not alleviated this can be found in: Burger et al Racial and ethnic disparities in human papillomavirus (HPV)- associated cancer burden with first- and second-generation HPV vaccines. Cancer. 2016 July 1; 122(13): 2057–2066. doi:10.1002/cncr.30007.
2) How prevalent are oral HPV infections in the US?Open or CloseAccording to the CDC:
“During 2011–2014, prevalence of any oral HPV was 7.3% among adults aged 18–69, 11.5% among men and 3.3% among women
Prevalence of any oral HPV was lower among non-Hispanic Asian adults (2.9%) and higher among non-Hispanic black adults (9.7%) compared with both non-Hispanic white (7.3%) and Hispanic adults (7.0%). For men, there was a similar racial and ethnic pattern.
Prevalence of any oral HPV was lowest among non-Hispanic Asian women. No significant difference in prevalence was seen among non-Hispanic white, non-Hispanic black, and Hispanic women.
Men had a higher prevalence of oral HPV than women, overall and within each race and Hispanic group.
Prevalence of high-risk oral HPV was lower among non-Hispanic Asian adults compared with other race and Hispanic groups:
During 2011–2014, prevalence of high-risk oral HPV was 4.0% among adults aged 18–69, 6.8% among men and 1.2% among women.
Prevalence was lower among non-Hispanic Asian adults, overall (1.7%) and among men (2.3%), than non-Hispanic white (4.2% all, 7.3% men), non-Hispanic black (4.3% all, 7.5% men), and Hispanic (3.4% all, 5.4% men) adults.
No differences were seen in prevalence of high-risk oral HPV by race and Hispanic group among women (1.1%–1.7%).
Prevalence of high-risk oral HPV was higher among men than women in all race and Hispanic groups, although the difference was not significant among non-Hispanic Asian adults.”
3) I hear that the incidence of HPV-caused oral cancers is soaring in men. What are the facts?Open or Close
Hokusai’s The Great Wave (Re-interpreted by Josh and Stewart Lyman)This is true. In the US, the number of yearly cases of HPV-caused oropharyngeal tumors has more than doubled between 1999 and 2015. It went from 6,996 cases in 1999 to 15,479 cases in 2015 (an increase of 121 percent).
According to the CDC, in 2015, oropharyngeal cancers made up 82% of all HPV-cancers in men, followed by anal cancers (12%) and penile cancers (6%).
The percentage of oropharyngeal cancers that were HPV positive increased from 16.3% in the period 1984–1989 to over 70% in 2000–2004 in the United States. This increase is highest among middle-aged white men (40 to 59 years old). Reference: Pytynia KB et al Epidemiology of HPV-associated oropharyngeal cancer Oral Oncol. 2014 May ; 50(5): 380–386. doi:10.1016/j.oraloncology.2013.12.019.
In oropharyngeal cancers, HPV 16 is the most common high-risk infection. HPV 16 accounts for 90% of HPV-related OPCs. Reference: Guo T et al The Potential Impact of Prophylactic HPV Vaccination on Oropharynx Cancer. Cancer. 2016 August 1; 122(15): 2313–2323. doi:10.1002/cncr.29992.
This topic has been widely covered in the popular press: e.g. Oral HPV More Common in Men Than Women NY Times 2012
Here are 5 recent papers focused on this issue:
HPV Related Disease Burden and Impact of HPV Vaccine (2018) by Martin Mahoney, MD, PhD Roswell Park Cancer Institute
Oropharyngeal Cancer Epidemiology by Kristina R. Dahlstrom, Ph.D. MD Anderson Cancer Center
Oropharyngeal Cancer: Clinical Implications of the HPV Epidemic by Erich M. Sturgis, M.D., M.P.H.
Epidemiological Trends of Head and Neck Cancer in the United States: A SEER Population Study Mourad et al J Oral Maxillofac Surg 75:2562-2572, 2017
Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States Chaturvedi et al J Clin Oncol. 2011 Nov 10; 29(32): 4294–4301
Prevalence of Oral HPV Infection in the United States, 2009-2010 by Gillison et al JAMA. 2012;307(7):693-703
This is not only happening in the US. Here’s a report of a similar phenomenon in Sweden:
Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: An epidemic of viral‐induced carcinoma?
4) Has there also been a big spike in HPV-caused oropharyngeal cancers in women?Open or CloseNot really. The number or women with HPV-caused oropharyngeal cancers climbed from 2,409 in 1999 to 3,438 in 2015 (a 40 percent increase). The ratio of male:female HPV-caused oropharyngeal cancers was 2.9 to 1 in 1999, but climbed to 4.5 fold by 2015. The incidence of these cancers is growing much faster in men than women, and is thought to follow increases in oral HPV infections in men.
According to the CDC, in 2015, oropharyngeal cancers made up only 14% of all HPV-cancers in women. The most prevalent HPV-cancer in women is cervical cancer (48%), followed by anal cancers (18%), vulval cancers (16%), and vaginal cancers (3%). Contrast this with men, where oropharyngeal cancers made up 82% of all HPV-cancers in men, followed by anal cancers (12%) and penile cancers (6%).
5) How are HPV strains shared between people?Open or CloseAccording to the CDC:
HPV is primarily spread by intimate skin to skin contact. You can be exposed to the virus by having oral, vaginal, or anal sexual contact with someone who is already infected. The virus can be transmitted by penetrative as well as non-penetrative sexual contact (genital-genital, oral-genital, anal-genital, oral-anal). Since many people have no symptoms of infection, it’s pretty common to become infected and to not even realize that has happened.
It had been thought that the hands can also transmit a genital, oral, or anal HPV infection. However, a new report in 2019 showed that the hands are actually a very unlikely source of viral transmission. Malagon et al Hand-to-genital and genital-to-genital transmission of human papillomaviruses between male and female sexual partners (HITCH): a prospective cohort study. The Lancet Infectious Diseases Feb. 2019 doi:10.1016/S1473-3099(18)30655-8
Most people will never develop symptoms of the infection as their immune systems will successfully eliminate the virus. However, some infected individuals will go on to develop either genital or anal warts, or to develop oral, anal, vaginal, vulval, penile, or cervical cancers. It can take years or even decades for these cancers to develop, making it very difficult to identify when a person actually became infected. Risk factors for catching HPV infections include an early age of first sexual intercourse, an increasing number of sexual partners, smoking, and having a compromised immune system.
Risk factors for catching HPV infections include:
Number of sexual partners. The more sexual partners you have, the more likely you are to contract a genital HPV infection. Having sex with a partner who has had multiple sex partners also increases your risk.
Age. Common warts occur mostly in children. Genital warts occur most often in adolescents and young adults.
Weakened immune systems. People who have weakened immune systems are at greater risk of HPV infections. Immune systems can be weakened by HIV/AIDS or by immune system-suppressing drugs used after organ transplants.
Damaged skin. Areas of skin that have been punctured or opened are more prone to develop common warts.
Personal contact. Touching someone's warts or not wearing protection before contacting surfaces that have been exposed to HPV — such as public showers or swimming pools — might increase your risk of HPV infection.
Source: Mayo Clinic
Risk factors specific for oral HPV infections include:
Oral sex. The prevalence of oral HPV infection was increased in subjects who had experience with oral sex as compared to those who did not.
Number of oral sex partners. Those with more oral sex partners had a higher incidence rate for HPV infection.
Smoking. This was significantly associated with oral HPV infections in both men and women
Source: See Shigeshi and Sugiyama Risk Factors for Oral Human Papillomavirus Infection in Healthy Individuals: A Systematic Review and Meta-Analysis J Clin Med Res. 2016 Oct; 8(10): 721–729. doi: 10.14740/jocmr2545w
6) How does the CDC define “high risk” strains of HPV (and related terms)?Open or CloseAny oral HPV: Oral rinse sample tested positive to one or more of the 37 HPV types listed under “All HPV types.”
High-risk oral HPV: Oral rinse sample tested positive to one or more of 14 high-risk HPV types (see definition) out of the 37 HPV types.
Any genital HPV in women: Vaginal swab sample tested positive to one or more of the 37 HPV types listed under “All HPV types.”
High-risk genital HPV in women: Vaginal swab sample tested positive to one or more of the 14 high-risk HPV types (see definition) out of the 37 HPV types.
Any genital HPV in men: Penile swab sample tested positive to one or more of the 37 HPV types listed under “All HPV types.”
High-risk genital HPV in men: Penile swab sample tested positive to one or more of the 14 high-risk HPV types (see definition) out of the 37 HPV types.
All HPV types (includes types detected by L1 consensus polymerase chain reaction): 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73, 81, 82, 83, 84, 89, or IS39.
High-risk HPV types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, or 68.
Source: CDC Prevalence of HPV in Adults Aged 18–69: United States, 2011–2014
7) What percentage of women in the US have cervical HPV infections? Is the vaccine helping prevent infections, cervical precancers, and actual cancers?Open or CloseThe prevalence of any cervical HPV infection is 26.8% for ages 14-59. 15.2% of women have are infected with high-risk (e.g. potentially cancer causing) strains of HPV, the most common being HPV16. The peak prevalence of cervical HPV infection is 44.8% in women ages 20-24, a few years following their sexual debut.
Reference: Guo T et al The Potential Impact of Prophylactic HPV Vaccination on Oropharynx Cancer. Cancer. 2016 August 1; 122(15): 2313–2323. doi:10.1002/cncr.29992.
The estimated lifetime risk for developing cervical cancer is only 0.68%, or about 1 in 147 women.
Howlader, et al SEER cancer statistics review, 1975-2009 (vintage 2009 populations). National Cancer Institute, https://seer.cancer.gov/archive/csr/1975_2009_pops09/.
New models of cervical cancer carcinogenesis suggest that HPV is necessary, but not sufficient, for the development of cervical cancer. The identification of a pathway contributing to cervical cancer involves activation of the YAP1 oncogene. See He et al A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms of Cervical Carcinogenesis. Cell Reports 26, 2636–2650, 2019. r(s). https://doi.org/10.1016/j.celrep.2019.02.004
Does the HPV vaccine really work to reduce cancer rates? Recent data says that it does:
As a result of the introduction of the HPV vaccine in 2006, we are starting to see declines in the prevalence of the HPV types that the vaccine targets. In one study, the prevalence of vaccine-type HPV decreased >90% in vaccinated women, demonstrating high effectiveness in a community setting, and >30% in unvaccinated women, providing evidence of herd protection.
See Kahn et al Substantial Decline in Vaccine-Type Human Papillomavirus (HPV) Among Vaccinated Young Women During the First 8 Years After HPV Vaccine Introduction in a Community. Clinical Infectious Disease 63, 1281 (2016) DOI: 10.1093/cid/ciw533
Also as a result of the introduction of the HPV vaccine in 2006, we are starting to see declines in the incidence of cervical pre-cancers both in those that are vaccinated as well as those who aren’t via herd immunity in both white and black women:
“In 10,206 cases, the proportion and estimated number of cases of HPV16/18-positive CIN2+ declined from 52.7% (1,235 cases) in 2008 to 44.1% (819 cases) in 2014 (P < 0.001). Declining trends in the proportion of HPV16/18-positive CIN2+ were observed among vaccinated (55.2%–33.3%, P < 0.001) and unvaccinated (51.0%–47.3%, P = 0.03) women; ages 18–20 (48.7%–18.8%, P = 0.02), 21–24 (53.8%–44.0%, P < 0.001), 25–29 (56.9%–42.4%, P < 0.001), and 30–34 (49.8%–45.8%, P = 0.04) years; CIN2 (40.8%–29.9%, P < 0.001) and CIN2/3 (61.8%– 46.2%, P < 0.001); non-Hispanic white (59.5%–47.9%, P < 0.001) and non-Hispanic black (40.7%– 26.5%, P < 0.001).”
See McClung et al Trends in Human Papillomavirus Vaccine Types 16 and 18 in Cervical Precancers, 2008– 2014 . Cancer Epidemiology, Biomarkers & Prevention DOI: 10.1158/1055-9965.EPI-18-0885
Finally, and most importantly, as a result of the introduction of the HPV vaccine in 2006, we are starting to see declines in the prevalence of cervical cancer in the young women first given the vaccine. The 4-year average annual incidence rates for cervical cancer in 2011–2014 were 29% lower than that in 2003–2006 (6.0 vs 8.4 per 1,000,000 people) among females aged 15–24 years, and 13.0% lower among females aged 25–34 years.
Guo et al Cervical Cancer Incidence in Young U.S. Females After Human Papillomavirus Vaccine Introduction. American Journal of Preventive Medicine Volume 55, Issue 2, 197–204, 2018. https://doi.org/10.1016/j.amepre.2018.03.013
In a study out of Finland, again based on the clinical trials of the HPV vaccine there, there was not a single case of ANY HPV+ cancer found in that cohort of 3,331 women given either the bivalent or the quadrivalent vaccine seven years after the trial began.
Luostarinen et al Vaccination protects against invasive HPV-associated cancers. Int. J. Cancer: 142, 2186–2187 (2018)
8) Why is the incidence of oral HPV infections bi-modal with respect to age, with peaks at 30 to 34 and 60 to 64?Open or CloseTo visualize this bimodal peak in HPV infection, see Fig. 4 in Gillison ML et al Epidemiology of Human Papillomavirus–Positive Head and Neck Squamous Cell Carcinoma J. Clin. Oncol. 33, #29, 3235-3242 DOI: 10.1200/JCO.2015.61.6995
According to Guo T et al The Potential Impact of Prophylactic HPV Vaccination on Oropharynx Cancer Cancer. 2016 August 1; 122(15): 2313–2323. doi:10.1002/cncr.29992., “Explanations for the first peak include a surge in oral HPV infection after sexual debut and at peak sexual activity. The second peak may be attributed to potential reactivation of dormant infections with immunosenescence, increased HPV exposure in divorced or widowed populations, and/or increased rates of persistent infection which increase overall prevalence.”
These are interesting hypotheses, but I don’t know of any data that really supports one idea over another regarding the second peak at age 60 to 64. I think it remains unexplained exactly why there are fewer cases of oropharyngeal cancer in those in the 35-59 year old age group. This may be a difficult question to answer epidemiologically.
9) Can the HPV virus that’s infected one area of your body migrate to another part?Open or CloseThe answer to this question is probably, but exactly how easily this occurs is unclear. The best evidence for this is the fact that survivors of HPV cancers are at a slightly increased risk of developing a second HPV-caused cancer (SEE BELOW). This could indicate that the virus has spread in the body, but it could also mean that the person is infected with two different cancer-causing strains of HPV, and those infections just happen to be in separate places. The only way to really answer this question is to do genetic sequencing of the virus from different body sites, and see if the exact same sequence is found at multiple sites. Even then, this would not guarantee that the virus has spread, because the person could have been infected at multiple locations during the initial infection.
10) Is the relative prevalence of different HPV strains found in cervical cancer similar around the world ?Open or CloseNo. While HPV 16 is the predominant strain in all countries where these studies have been done, the percentage of other strains differs markedly. HPV was found in 99.7 percent of cervical cancer samples analyzed worldwide. See Waldboomers et al Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J. Pathol. 189, 12-19, 1999.
11) Do the partners of those diagnosed with HPV positive oral cancers have a higher incidence of oral infection with a cancer-causing strain of HPV than the general population?Open or CloseNo. HPV status was looked at in the female and male partners of men who had HPV+ oral cancers. The researchers found that the partners had comparable oncogenic oral HPV prevalence (i.e. they were HPV 16+) compared with members of the general population of the same age (1.2% v 1.3%). No precancers or cancers were identified during partner oral cancer screening examinations either.
Reference: D’Souza et al Oral human papillomavirus (HPV) infection in HPV-positive patients with oropharyngeal cancer and their partners. J Clin Oncol. 10, 2408-15, 2014. doi: 10.1200/JCO.2014.55.1341.
12) Are survivors of HPV-assocated cancers at increased risk of developing a second HPV-associated cancer compared to the general population?Open or CloseUnfortunately, yes. Survivors of HPV-associated cancers are at an increased risk of developing HPV second primary cancers (HPV-SPCs). Among both women and men, the risk of developing HPC-SPC at the original cancer site was higher than that of developing HPC-SPC at a different cancer site. Among women with index vaginal, vulvar, and anal cancers, the risk for all HPV-SPCs remained high. The HPV-SPC risk was lowest among women with index cervical cancer. Among men, the oropharyngeal SPC risk was elevated after index penile and anal cancers. Given the large difference in the HPV-SPC risk between survivors of HPV-associated cancers and that of non–HPV-associated cancers, it is likely that persistent HPV infection contributes to the development of HPV-SPCs among survivors of HPV-associated cancers.
Reference: Suk et al Trends in Risks for Second Primary Cancers Associated With Index Human Papillomavirus–Associated Cancers. JAMA Network Open. 2018;1(5):e181999. doi:10.1001/jamanetworkopen.2018.1999 (FREE ARTICLE)
13) Which happens more easily: men genitally transmit an HPV infection to women, or women genitally transmit the virus to men?Open or CloseThe available data indicates it’s a much more efficient process (3 times as much) for women to give the virus to men rather than vise-versa. In addition, according to the paper, “The penis shaft was the primary source of transmission to the cervix; the cervix and urine were the primary sources of infection to male genitals. Sexual transmission also involved the scrotum, the anus of women, and the hands of both sexes. The oral cavity and semen were not involved in transmission. The anus of women was both a major source and target of heterosexual transmission. We observed consistency between penis-to-female anus transmission and reported anal intercourse during the corresponding period.”
Source: BY Hernandez et al Transmission of Human Papillomavirus in Heterosexual Couples. Emerg Infect Dis. 2008 Jun; 14(6): 888–894. doi: [10.3201/eid1406.070616.2]
14) Is there a difference in the ability of men and women to generate antibodies in response to HPV infections?Open or CloseIt appears there is a big difference here. Researchers looked at the prevalence of antibodies to HPV strains 16 and 18 (these are cancer causing strains) and strains 6 and 11 (that can cause genital warts, not cancer) in three groups that have had sex, but had not been vaccinated against HPV. The groups were women, men who had sex with men i.e. gay or bisexual (MSM), and men who had sex with women (MSW). Results of the study showed that the level of antibodies to HPV among MSM and women were comparable at 42.6% and 37.1%, respectively. In contrast, the ability to generate antibodies to HPV was greatly reduced among MSW at only 13.2%. Additionally, the researchers found that the ability to generate antibodies increased with the number of lifetime sexual partners in all three groups. Why the gender differences? Researchers believe it is due to the nature of the tissues where the infections take place. Antibodies are more likely to be generated after exposure at non-keratinized (mucosal) surfaces compared to keratinized epithelium. Thus, if infection occurs in the anus, or inside the vagina, these represent exposure at mucosal surfaces. An infection on the penis would be an example of an infection on a keratinized epithelial surface. Mucosal tissues are those that are likeliest to spread infection.
Source: Lewis RM, et al. Seroprevalence of human papillomavirus 6/11/16/18 among self-identified gay/bisexual men who have sex with men, men who have sex with women, and females, United States, 2003–2010. Clin Infect Dis. 2018; 10.1093/cid/ciy1002.
What’s unclear to me in all of this is antibody prevalence related to oropharyngeal infection (also a mucosal surface). Thus, men who have vaginal sex with women are relatively resistant to infection on the keratinized surface of the penis. In contrast, men who perform oral sex on women should be quite prone to infection with HPV because of the oral mucosa in their mouths. Why this doesn’t translate into the generation of antibodies in men is unclear to me. According to a different source, “the fact that infections in other mucosal sites of the body (e.g. the mouth) also elicit antibody responses that cannot be distinguished from those arising in the anogenital area.” Separating out responses to oral vs. anogenital exposure as measured via serum antibody levels seems a very complex undertaking that is unlikely to provide a clear answer because sexual behavior differs widely between individuals.
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 90. IARC Working Group on the Evaluation of Carcinogenic Risk to Humans.
Lyon (FR): International Agency for Research on Cancer; 2007.
15) How old are most people when they are diagnosed with the various HPV-caused cancers?Open or CloseWith one significant exception, most of the cases of HPV-caused cancers are found in older adults.
The exception is cervical cancer, a disease that hits women during their reproductive years. Here’s the data from the CDC website:
The median age at diagnosis (the age at which half of cancer patients were older and half were younger), is:
49 years for HPV-associated cervical cancer.
67 for HPV-associated vaginal cancer.
66 for HPV-associated vulvar cancer.
69 for HPV-associated penile cancer.
62 among women and 59 among men for HPV-associated anal cancer.
62 among women and 61 among men for HPV-associated oropharyngeal cancers.
The graphs below illustrate the trends more clearly. Note that the scale on the Y axis is different on the two graphs. The other key point is that the highest incidence rate of all HPV-caused cancers is associated with oropharyngeal cancers in men. The peak rate is 2.5X as large as the peak rate for cervical cancer in women.Rates of HPV-Associated Cancers and Age at Diagnosis Among Women in the United States per Year, 2011–2015Rates of HPV-Associated Cancers and Age at Diagnosis Among Men in the United States per Year, 2011–2015
16) Does tonsillectomy prevent the development of tonsil cancer? Would it be recommended for this purpose?Open or CloseTonsillectomy does NOT prevent the development of tonsil cancer, but it did reduce the number of cases of tonsil carcinoma diagnosed before age 60 by 85%, and any tonsil carcinoma by 60%. According to the authors, “This observation is made with caution. Tonsillectomy is not a surgical procedure to be discounted and can lead to both minor and major complications, including death. Careful consideration of the relatively low incidence of oropharyngeal carcinoma, potential morbidity and mortality of tonsillectomy, and promising potential impact of the prophylactic HPV vaccine is warranted.”
Not surprisingly, tonsillectomy does NOT prevent other HPV-caused oropharyngeal cancers (or HPV-caused cancers in other tissues) from developing. This fact, coupled with the surgical risks of and expenses of tonsillectomy, are why I don’t expect to find anyone proposing to do tonsillectomies prophylactically to prevent tonsil tumors.
Fakhry et al The Impact of Tonsillectomy upon the Risk of Oropharyngeal Carcinoma Diagnosis and Prognosis in the Danish Cancer Registry. Cancer Prevention Research, 1-7, 2015 doi: 10.1158/1940-6207.CAPR-15-0101
17) Do women and men who’ve been diagnosed with pre-cancerous HPV positive lesions have an increased risk of developing HPV-caused cancers at other anatomical sites?Open or CloseYes they do, according to a Scottish study: “All cases of pre-invasive penile, anal, vulval, and vaginal disease diagnosed in 1990-2015 were identified within the NHS pathology databases in the two largest NHS health boards in Scotland.” “Among 69714 females in Scotland diagnosed with CIN3 (890360.9 person-years), 179 developed non-cervical HPVaC. CIN3 cases were at 3.2-fold (95% CI: 2.7 to 3.7) increased risk of developing non- cervical HPVaC, compared to the general female population. Among 1235 patients diagnosed with non-cervical pre- invasive disease (9667.4 person-years), 47 developed HPVaC. Individuals with non-cervical pre-invasive disease had a substantially increased risk of developing HPVaC - 15.5-fold (95% CI: 11.1 to 21.1) increased risk for females and 28-fold (11.3 to 57.7) increased risk for males. We report a significant additional risk of HPV-associated cancer in those have been diagnosed with pre-invasive HPV- associated lesions including but not confined to the cervix.”
I didn’t find this result surprising because they’re looking at a population of patients that has already shown itself to be incapable of fighting off their HPV infections. As a result, I’d expect this group to have a much higher incidence of HPV-caused cancers than the general population.
Source: Kavanagh et al Increased risk of HPV-associated genital cancers in men and women as a consequence of pre-invasive disease. Int J Cancer. 2019 Jan 16
18) What’s the overall risk of developing an HPV-associated cancer in your lifetime, and what’s the risk of dying of one of these cancers?Open or CloseFor individuals not vaccinated against HPV, the cumulative risk of developing an HPV-associated cancer was 1.4% in white women, and about 0.98% in white men. Thus, about 1 in 71 white women will develop one of these cancers, and about 1 in 100 white men will. If we focus just on cervical cancer, the estimated lifetime risk for developing cervical cancer is only 0.68%, or about 1 in 147 women.
Howlader, et al SEER cancer statistics review, 1975-2009 (vintage 2009 populations). National Cancer Institute, https://seer.cancer.gov/archive/csr/1975_2009_pops09/.
For individuals not vaccinated against HPV, the cumulative risk of dying from an HPV-associated cancer was
0.24% for females and 0.20% for males, where Non-Hispanic Black individuals faced the highest burden for both sexes (i.e., 0.32% and 0.25%, respectively). Thus, about 1 in 417 white women will die one of these cancers, and about 1 in 500 white men will.
The paper below contains this data, along with data for other racial groups. It also estimates the risks following immunization with the bivalent and nonavalent HPV vaccines.
Data from: Burger et al Racial and ethnic disparities in human papillomavirus (HPV)- associated cancer burden with first- and second-generation HPV vaccines. Cancer. 2016 July 1; 122(13): 2057–2066. doi:10.1002/cncr.30007.
19) Does immunization with the HPV vaccine lead to an increase in type I diabetes?Open or CloseNo. Researchers examined all potential cases of type 1 diabetes that were identified from members of Kaiser Permanente Northern California (KPNC) aged 11-26 years at any time from June 2006 to December 2015. The analysis of DM1 included 911,648 people. No increased risk was found for the development of DM1 following HPV vaccination.
Reference: Klein et al Long term risk of developing type 1 diabetes after HPV vaccination in males and females. Vaccine, March 05, 2019
20) I hear that there’s been an important new development in classifying HPV+ head and neck cancers into two groups with different outcomes? What’s the story, and what does the data say?Open or CloseThis is a developing story with some important potential clinical applications. In short, while most HPV+ H&N cancer patients do well with standard treatments, a small percentage don’t (they are more similar to HPV negative H&N cancer patients in this regard). Researchers at MD Anderson Cancer Center examined the expression of a large collection of cellular proteins that interact with HPV to figure out what distinguishes those patients who respond well from those who don’t. In the end, they found a subset of 38 genes whose expression correlated with outcomes to treatment. How is this useful? Two implications are is that it may eventually enable doctors to identify patients before treatment who are NOT likely to respond to standard therapies, and thereby shunt them into different therapeutic regimens. It may also enable doctors to ID patients who are likely to have good outcomes with standard therapy for de-escalation treatments. The hope is that this will enable patients to get lower doses of damaging radiation (and therefore experience less tissue damage), yet still achieve good survival outcomes. This will need to be established in future clinical trials.
Here are the references for those wanting to learn more:
Gleber-Netto et al. Variations in HPV function are associated with survival in squamous cell carcinoma. JCI Insight. 2019;4(1):e124762. https://doi.org/10.1172/jci.insight.124762.
This paper is a more readable explanation of what the paper above is suggesting:
R. Hepp New Biomarker Reveals HPV Function in Head & Neck Cancers. Oncology Times: March 5, 2019 - Volume 41 - Issue 5 - p 17–18 doi: 10.1097/01.COT.0000554320.58842.75
21) Are head and neck cancer patients who are HPV+ and receive radiation as part of their treatments at increased risk of developing strokes years later?Open or CloseMaybe. The authors of the paper below concluded that HPV-positive status is associated with an increased risk of stroke or transient ischemic attack following radiation treatment for head and neck cancer. The authors themselves raise some caveats regarding this in terms of both how the patients were chosen for the analysis as well as which ones were available for follow up. I had some reservations about the conclusions drawn. First, there is no comparison (i.e. a control group) with a group that matched the H&N cancer patients. How would "normal" people (people with and without HPV infection, but no cancer) would have had strokes or TIAs over that same time period? Similarly, how would cancer patients that got radiation at some other location (e.g. prostate) compare to this group? Is it the radiation, where the radiation goes, or something else? Hard to say here. I also noticed that there was a higher proportion of men in the HPV-positive group, and maybe the increased stroke/CVE risk simply reflects having more men in that group. Finally, I'm not sure how actionable this data is. After all, no one would turn down the radiation therapy if it was needed just to have a lower risk of stroke/CVE.
Addison, D. et al Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer. J Am Heart Assoc. 2017;6:e006453. DOI: 10.1161/JAHA.117.006453. (FREE paper)