understated cervical cancer mortality and hpv in men

2 recent articles looked at US cervical cancer mortality and hpv infections in men.

1. The New York Times reported a huge racial gap in cervical cancer deaths in the United States (see https://www.nytimes.com/2017/01/23/health/cervical-cancer-united-states-death-toll.html?_r=0 ). They referred to an article which calculated a much higher death rate from cervical cancer overall in the US than previously found, with an increased disparity between black and white women (see cervical ca inc mortality cancer2017 in dropbox, or DOI: 10.1002/cncr.30507 ).

Details:

-- the age-standardized rate for cervical cancer death reported by the National Center for Health Statistics from 2000-2012 was 3.2/100K in white women and 5.7/100K in black women

-- however, these results were not corrected for the prevalence of hysterectomies, and given that hysterectomies are significantly more common in black women, the above statistics understated the cervical cancer death rates (since these cancers are essentially eliminated in people who've had hysterectomies for benign reasons, especially if the cervix is removed).

Results:

-- the overall prevalence of hysterectomies was 20% for women >20 years old, higher in black women for all ages between 45-69, peaking for both white and black women at ages 65-69, but this peak hysterectomy rate was 58% of black women vs 43% of white women [remarkably high numbers overall and shockingly so for older black women!!]

-- Correcting for the prevalence of hysterectomies, the mortality rate was 10.1/100K in black woman and 4.7/100K in white women.

-- Based on this, the disparity in mortality rates was underestimated by 44% over the published NCHS numbers.

-- The highest corrected rate was in black women > 85 years, with a death rate of 37/100K vs 11/100K for white women!!!

-- Using this corrected analysis, the rate of cervical cancer deaths in white women decreased at 0.8% per year, whereas for black women the annual decrease was 3.6%.

Commentary:

-- each year more than 12,000 women in the US are diagnosed with cervical cancer and more than 4000 women die from it.

-- for the women in this study, the likelihood of a supracervical hysterectomy (ie, leaving the cervix) was <2% (data from before 2004), though now is closer to 4-7.5%. So more individual data, even if available, would not have altered the results much

-- Cervical cancer is largely preventable through screening, and screening rates may be lower in poor and minority areas, although published results on this are equivocal. The data are clearer that black women tend to present with more advanced disease and may receive different treatments than white women, eg less surgery and more radiation for the same stage of cancer. For example, a recent large study of more than 15,000 patients with advanced cervical cancer found that more than half did not receive treatment considered to be standard of care, mostly those who were black and poor.

-- The corrected cervical cancer mortality rates in black American women is similar to those of many resource-poor countries in Latin America, Asia (excluding Japan), the Caribbean, and Africa (including sub-Saharan Africa). For white women, their corrected cervical mortality rates are similar to those of Europe, Australia, and Japan

-- the corrected mortality is significantly higher in black vs white women in all age groups, except those aged 20-29 and 35-39 (though increases pretty dramatically in women older than this)

-- Some of the methodologic weaknesses of the study include the potential for biases related to incomplete data and the merging of 2 unrelated databases with very different methodologies. The data on age-standardized death rates came from the National Center for Health Statistics (they also looked at the SEER database, which did not include every state and notably did not include Louisiana), whereas the data on hysterectomy prevalence came from the Behavioral Risk Factor Surveillance System survey, which is based on interviews.

-- It was quite striking to me when I was working in Chicago many many years ago that a very large number of my middle-aged to older black female patients had had hysterectomies when living in the Southern US, but were unaware they even had the surgery (many reported having had some surgery, but were never told that the doctors had done a hysterectomy). We were told that this was a not uncommon method of enforced birth control for black women.... So, since some were unaware they even had the surgery (and may be part of the older women now), the racial disparity may be even greater.

So, it is quite striking that black women in the United States have such a high death rate from cervical cancer. And, perhaps a real concern is that with the repeal of the Affordable Care Act, which does cover such screenings, there may be less access for many people for appropriate screenings. In addition, I am very concerned that the upcoming, likely attacks on Planned Parenthood and other clinics providing cervical cancer screening etc, will decrease access especially for poor women and women of color.

Relevant prior blogs:

http://gmodestmedblogs.blogspot.com/2016/10/cervical-screening-guidelines-from-asco.html  which reviews the American Society of Clinical Oncology guidelines

http://gmodestmedblogs.blogspot.com/2016/10/cervical-cancer-screening-less.html  presents data from a study in the Netherlands, suggesting that negative cervical HPV screening in women over age 40 supports a strategy of screening every 10 years

http://gmodestmedblogs.blogspot.com/2014/10/whither-pelvic-again.html  which was a review of urinary screening for HPV, with my concern that clinicians will be doing far fewer pelvic exams (which certainly has its pluses, since these can be invasive and uncomfortable procedures for women), but with the caveat that I have seen several younger clinicians feeling less comfortable doing pelvic exams even when clinically indicated

http://gmodestmedblogs.blogspot.com/2016/07/pap-smears-post-hysterectomy-in-hiv.html  presents a study suggesting that we should do Pap smears in HIV patients, even post-hysterectomy

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2. Another article came out looking at the prevalence of genital HPV infections as well as vaccination rates in US adult men, from the National Health and Nutrition Examination Survey (NHANES) of 2013- 2014 (see  hpv in men jamaonc2017in dropbox, or doi:10.1001/jamaoncol.2016.6192).

Details:

-- NHANES collects information of representative cross-section samples of the US population.

-- 1868 men aged 18 to 59 were examined and DNA was extracted from self-collected penile swab specimens for HPV genotype. 

-- Demographic and vaccination information was gathered by self-report.

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Results:

-- the overall general HPV infection prevalence in males aged 18-59 was 45.2% (ie, 34.8 million men).  bimodal pattern, with peaks age 28-32 and another 58-59

-- the infection prevalence with at least one high risk HPV subtype by DNA testing was 25.1%

-- the overall prevalence of infection for subtypes covered by the HPV-9 valent vaccine was 15.1% (the 9-valent vaccine covers 90% of subtypes responsible for cervical cancer in women)

-- the specific very high-risk subtype prevalences: 4.3% for HPV-16 (3.3 million men), 1.7% for HPV-18 (1.3 million men)

-- in vaccine-eligible men, the prevalence of infection with at least one HPV strain targeted by the HPV-4 valent vaccine was 7.1% and by the HPV 9-valent vaccine was 15.4%

-- among vaccine-eligible men, HPV vaccination coverage was 10.7% (ie more than 25 million vaccine-eligible men did not receive the vaccination)

Commentary:

--HPV is the most commonly known sexually transmitted infection in the US. An estimated 79 million people in the US are infected with HPV, half of new infections occurring before age 24. There was a study about 10 years ago finding that 50% of women in their first year at college acquired HPV infection. In men, an estimated 160,000 are infected annually with low-risk HPV infections

-- in men, an estimated 9000 HPV-related cancers occur annually, responsible for 63% of penile cancers, 91% of anal cancers and 72% of oropharyngeal cancers (the oral HPV infection rates are around 10% for men and 4% for women). HPV can also cause recurrent respiratory papillomatosis

-- men seem to clear HPV infection pretty quickly, with a study of 290 men finding that the 12-month risk of acquiring a new infection was 29%, with the median time to clearance being 5.9 months (Giuliano AR. J Infect Dis 2008; 198: 827). so, it seems likely that the point prevalence in the above study significantly understates the life-time acquisition rate for HPV, which is similar to that of women.

--BUT, the major public health issue for men is that they can transmit this infection to women, potentially leading to cervical cancer, with a significant morbidity and mortality (as in first article above)

--the CDC therefore published their recommendations for HPV vaccination: females aged 11 to 26; males aged 11 to 21, but from 21-26 being "recommended for persons with a risk factor (medical, occupational, lifestyle, or other indication"). Probably makes sense to support male vaccination til age 26, similar to the female recommendations

so, bottom line: these studies are very concerning, since on the one hand HPV infections are wide-spread and the number of unvaccinated men who are vaccine-eligible is staggering; on the other hand, cervical cancer death rates are quite high in the US and with a pretty dramatic black-white differential.