HPV FAQ

Contents

How common is HPV?

Between 20% and 50% of Americans are currently infected with HPV; infection is most common in the 20-24 age range.

Some regions have higher rates of HPV infections. In one province in South Africa, 74.6% of women have HPV.

What diseases can HPV cause?

HPV is known to cause several diseases: and is suspected of involvement in other diseases:

What types of HPV are there?

There are over a hundred types, but only a few cause disease.

HPV6 and HPV11 account for most genital warts.

HPV16 and HPV18 account for about 70% of cervical cancer.

Types 31, 33, 45, 52, 58 account for about another 20% of cervical cancer.

What types of HPV does the vaccine prevent?

Gardasil (also known as Silgard) prevents types 6, 11, 16, and 18. Cervarix prevents types 16 and 18. Both protect against the types that cause about 70% of cervical cancer.

How common is HPV-caused cancer?

HPV causes about 26,000 cancers per year in the United States, and about 610,000 cancers per year worldwide.

The lifetime risk of cervical cancer is 1 in 152 in the United States. It is higher in countries without widespread screening programs; for instance, it is 1 in 40 in South Africa.

The lifetime risk of anal cancer 1 in 500 in the United States.

How does HPV cause cancer?

HPV carcinogenesis is complex.

According to "The Role of HPV E6 and E7 Oncoproteins in HPV-associated Cervical Carcinogenesis",

"The abilities of high-risk HPV E6 and E7 proteins to associate with the tumor suppressors p53 and pRB, respectively, have been suggested as a mechanism by which these viral proteins induce tumors."
According to " Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability",
"Whole-genome sequencing revealed HPV integrants flanking and bridging extensive host genomic amplifications and rearrangements, including deletions, inversions, and chromosomal translocations."
And according to "APOBEC-Mediated Cytosine Deamination Links PIK3CA Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development",
"we have uncovered a critical role for APOBEC-mediated mutagenesis in HPV-driven tumor development"
For much more, see Google Scholar.

How did the FDA decide to approve the vaccine?

Gardasil went through the usual phases of clinical trials. Merck conducted six phase I and phase II clinical trials starting in 1997, and two large phase III trials (FUTURE I and FUTURE II) between 2002 and 2007.

The FDA reviewed the clinical trial results for safety and efficacy, and approved Gardasil for use against cervical cancer and genital warts in women in 2006, and against anal cancer in anyone aged 9 through 26 in 2010.

How safe is the vaccine (Gardasil)?

Four large studies of about 100,000, 190,000, 200,000, and 300,000 vaccinated women have been done since the vaccine was approved. None of the studies found any significant safety problems with the vaccine.

Since fainting is possible after any vaccination, patients should sit for 15 minutes after being vaccinated.

The shot often hurts for a few days. A study on tolerability which emailed questionnaires to 3552 girls after each dose found that about 1 in 8 respondants said they experienced pronounced pain, stiffness, or swelling that started within 3 days and lasted about 1 to 5 days.

About 1 in 100,000 people may have an allergic reaction to the vaccine. Most recover without incident.

The lifetime risk of contracting cervical or anal cancer (1 in 152 and 1 in 500, respectively) is much higher than any of the serious risks indentfied so far with the vaccine.

See hpv.kegel.com/safety for more info on hpv vaccine safety.

How many doses are needed?

The vaccines were originally approved for use as a three dose series, with a second shot at 1 or 2 months, and a third shot at 6 months.

Recent research indicates that two doses given six months apart may suffice if given by age 13. As a result, the UK is switching to a two-dose schedule.

The United States is considering this change as well, but will probably stick with the three-dose schedule until about 2016.

Who should be vaccinated?

The following two groups get the most benefit from the vaccine:
  1. Boys and girls between about age 10 and age 14 have not yet been infected ( girls vaccinated by age 14 have about 75% fewer abnormal pap smears at first screening, whereas older girls, who have presumably already been infected, get less benefit).
  2. Women who are being treated for abnormal pap smears (since the vaccine has been reported to reduce recurrence).
But people outside these groups may still benefit, and vaccine is approved in the US for people up to age 26. See the CDC/ACIP recommendations.

Who should not be vaccinated?

If you had hives or some other allergic reaction within a week or so of receiving the first or second dose of an HPV vaccine, you probably want to avoid taking any further doses, just in case.

According to Merck,

"Gardasil is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of Gardasil."

According to Glaxo,

"You should not get Cervarix if you have or have had an allergic reaction to a previous dose of Cervarix, or an allergy to any of the ingredients in Cervarix (listed below)."

Is the new cobas HPV test going to replace Pap tests? Is that good?

No, it won't quite replace Pap tests, but there will be fewer of them.

The proposed new test starts off by checking for HPV16 and HPV18 individually, as those are the two highest risk strains. It also checks for all other high risk strains as a group. It doesn't check for low risk strains, which is fine, as they generally don't cause cancer.

Here's how the test is supposed to be used:

"In women 25 years and older, the cobas HPV Test can be used as a first-line primary cervical screening test to detect high risk HPV, including genotyping for 16 and 18. Women who test negative for high risk HPV types by the cobas HPV Test should be followed up in accordance with the physician's assessment of screening and medical history, other risk factors, and professional guidelines. Women who test positive for HPV genotypes 16 and/or 18 by the cobas HPV Test should be referred to colposcopy. Women who test high risk HPV positive and 16/18 negative by the cobas HPV Test (12 Other HR HPV positive) should be evaluated by cervical cytology to determine the need for referral to colposcopy."
In other words, if it finds the highest risk strains (HPV16 or 18), your doctor will have you get a colposcopy; if it finds other high risk HPV, your doctor will give you a Pap test.

According to the FDA review packet, the new test finds more cancer using fewer colposcopies than does current standard practice.

Do I need to keep getting screened after being vaccinated?

Yes. Current vaccines only prevent 50%-70% of cervical cancers, so you still need to get a pap test every three years as recommended by the CDC.

Since I need to keep getting pap tests anyway, why do we even bother with the vaccine?

Pap tests, even when combined with HPV tests, can only detect cervical cancer, and only in women eligible for screening (in the UK, women under 25 are not screened). But according to the CDC, only 11,500 of the 25,900 HPV-caused cancers annually in the US are of the cervix. For those other cancers, pap smears are not an option, and the vaccine is likely to offer good protection.

Also, when cervical cancer screening finds an HPV-caused lesion, it has to be surgically removed to prevent the cancer (by cutting, freezing, or burning). Screening finds about 300,000 cases of HSIL (CIN2/CIN3) annually in the US, leading to approximately half a million LEEP procedures each year. Women vaccinated when they were age 9-14 have about 55% lower risk of CIN2 or CIN3 and thus about 55% lower risk of needing surgery to prevent cancer.

See also "Prophylactic HPV Vaccines: Current Knowledge of Impact on Gynecologic Premalignancies" by Diane Harper, which points out

"While Pap testing is effective, there still remain five specific challenges. First, screening must be done repeatedly over most of the woman's lifetime. Second, false negatives can occur; 30% of women developing cervical cancer having had a history of normal cytology screens (Sawaya and Grimes, 1999). Third, abnormal cytology causes much anxiety for many women (Rogstad, 2002). Fourth, for those women whose screening leads to a diagnosis of CIN 2/3, treatment with loop electrosurgical excision procedure (LEEP) can lead to an increased risk in subsequent pregnancies of preterm delivery, low birthweight infants, premature rupture of membranes, and operative delivery at a rate of 70-300% increase (Arbyn et al., 2008). Lastly, there is no lifetime protection from future HPV infections from her natural infection, leaving a woman at a 3-12 fold increased risk of other anogenital cancers about 10 years later (Edgren and Sparen, 2007)."
(Note: that paper also contains a much lower estimate of what portion of HPV-caused cancers are noncervical (12% vs. 55%). The difference may be explained in part by our greater knowledge since then of the role of HPV in throat cancer.)

How long does the vaccine protect against HPV?

At least eight years, probably longer.

Two trials watched Gardasil for six years and for eight years. One watched Cervarix for 9 years (see also here.)

None of these studies has found when the vaccines really wear off yet, but long-term studies are continuing, and eventually we may know how long it lasts.

Booster shots are not currently recommended, but if it turns out that protection wears off after ten years, that may change. There is some evidence Gardasil works as a booster after 5 years and after 8.5 years.

See also "Long-Term Studies of Quadrivalent HPV (qHPV) Vaccine Effectiveness".

How many girls need to be vaccinated to prevent one case of cancer?

The number of girls vaccinated per prevented case of cervical cancer was estimated by one paper to be between 250 and 600, and by another paper to be between 324 and 480. (These studies were for the US and Canada; in the developing world, where screening is less widespread, the number is probably lower.)

Do condoms prevent HPV infections?

If used every time, they can cut risk by 25% to 50%.

"Condom use and the risk of genital human papillomavirus infection in young women" found

In women reporting 100 percent condom use by their partners, no cervical squamous intraepithelial lesions were detected in 32 patient-years at risk, whereas 14 incident lesions were detected during 97 patient-years at risk among women whose partners did not use condoms or used them less consistently.

"Determinants of prevalent human papillomavirus in recently-formed heterosexual partnerships: A dyadic-level analysis" found

Dyads that always used condoms with previous partner(s) were 27% (95% CI: 9-42%) less likely to have HPV.

My son or daughter is not yet sexually active. Why does he or she need the vaccine?

The vaccine requies three doses over six months to reach full protection. When romance strikes, it happens in a hurry, and you want to already be protected by then.

Girls vaccinated by age 14 had about 75% fewer abnormal results at their first pap test as their unvaccinated peers... but girls vaccinated by age 15 were only half as well protected.

Since the virus can be transmitted by just touching an infected area, you don't have to have "sex" to catch it. Two studies found between 2% and 46% of young women already had HPV by the time they first have intercourse. You can even catch HPV from open-mouth kissing. So even kids whose parents don't consider them sexually active are at risk.

Virginity pledges don't seem to protect against STDs such as HPV, either; see "After the promise: the STD consequences of adolescent virginity pledges" (full text).

Is vaccination cost effective?

It depends on how much the vaccine costs, how long it protects, and how broad the protection is. "Modeling cervical cancer prevention in developed countries" said
"Under assumptions of lifelong vaccine immunity, the vast majority of published cost-effectiveness analyses have suggested that targeting pre-adolescent girls (ages 12 or younger) with an HPV-16/18 vaccine is very attractive in the context of current screening."

Is it safe to get the HPV vaccine if you already have HPV?

Short story: Yes, the vaccine is still safe, and will still protect you against the strains it covers that you haven't had yet.

Long story: "CDC HPV Vaccine Information for Young Women" says

Ideally females should get the vaccine before they become sexually active and exposed to HPV. Females who are sexually active may also benefit from vaccination, but they may get less benefit. This is because they may have already been exposed to one or more of the HPV types targeted by the vaccines. However, few sexually active young women are infected with all HPV types prevented by the vaccines, so most young women could still get protection by getting vaccinated.

Has Gardasil already begun lowering the prevalence of HPV infections?

Yes.

Both the US and Australia have done studies to measure what percent of girls and women have HPV before and after the vaccine was introduced.

The United States has recommended vaccinating girls since 2006. A study of the National Health and Nutrition Examination Surveys from 2003 to 2010 said

Results: Among females aged 14-19 years, the vaccine-type HPV prevalence (HPV-6, -11, -16, or -18) decreased from 11.5% (95% confidence interval [CI], 9.2-14.4) in 2003-2006 to 5.1% (95% CI, 3.8-6.6) in 2007-2010, a decline of 56% (95% CI, 38-69). Among other age groups, the prevalence did not differ significantly between the 2 time periods (P> .05). The vaccine effectiveness of at least 1 dose was 82% (95% CI, 53-93).

Conclusions: Within 4 years of vaccine introduction, the vaccine-type HPV prevalence decreased among females aged 14-19 years despite low vaccine uptake. The estimated vaccine effectiveness was high.

Australia has been actively vaccinating girls since 2007. "Fall in Human Papillomavirus Prevalence Following a National Vaccination Program" says

HPV genoprevalence in women aged 18-24 years attending family planning clinics in the prevaccine period (2005-2007) was compared with prevalence among women of the same age group in the postvaccine period (2010-2011). ... The prevalence of vaccine HPV genotypes (6, 11, 16, and 18) was significantly lower in the postvaccine sample than in the prevaccine sample (6.7% vs 28.7%; P < .001), with lower prevalence observed in both vaccinated and unvaccinated women compared with the prevaccine population (5.0% [adjusted odds ratio, 0.11; 95% confidence interval, 0.06-0.21] and 15.8% [adjusted odds ratio, 0.42; 95% confidence interval, 0.19-0.93], respectively).

Has Gardasil already begun lowering the incidence of genital warts?

Yes.

We already knew from clinical trials of Gardasil that it prevents about 80% of genital warts when given before exposure to HPV. Now, several studies have measured how effective it is in real world national immunization programs. For instance:

Has Gardasil already begun lowering the incidence of abnormal pap smears?

Yes.

We already knew from clinical trials of Cervarix and of Gardasil that HPV vaccines, when given before exposure to HPV, are 85%-100% effective against CIN3 caused by HPV16 and HPV18. Now, four studies have measured how effective they are in real world national immunization programs:

These studies were not large enough to measure the vaccine's benefit precisely, but it's safe to say that vaccination reduces the risk of CIN3 by about half, and that vaccinating by age 14 gives even more protection.

Since CIN2 and CIN3 are treated by surgically removing part of the cervix, an operation that carries risks of complications, women will directly benefit from this reduction.

Since about 50% of untreated CIN3 progresses to cervical cancer, preventing CIN3 is quite likely to prevent some cervical cancer. And since about half of all cervical cancer in the US occurs in women who haven't been properly screened, this is true even in countries with screening programs.

Has Gardasil already begun lowering the incidence of cervical cancer?

Not yet.

Studies of the effect of national vaccination programs continue. We should see something noticable at least by the time the first group of girls to be vaccinated hits age 27 or so. (That's because cervical cancer rates jump to high levels at about that age.) That should happen about the year 2022.

One of the researchers in the long-term followup studies of Cervarix says:

" [with] the country-wide, population-based Finnish Cancer Registry... We have >= 80% power to provide data on vaccine efficacy against CIN3 in 2014, against ICC in 2022 and against other HPV- associated cancers in 2024"

If the vaccine is so effective, why does it only lower risk of cancer by half?

In clinical trials, the vaccines were completely effective against CIN3 caused by HPV16 or HPV18 -- when given to women who had never been exposed to HPV before.

In the real world, when given to the average young woman aged 15 to 26, the vaccine is less effective because (a) many of these women have already been exposed to HPV, and (b) about 30% of cervical cancer is caused by types of HPV that the vaccine doesn't target.

At age 11-12, and even as late as age 14, most girls have not yet been exposed to HPV. Thus vaccinating at ages 11-12 should provide nearly 100% protection against HPV16/18, and about 70% protection against CIN3 caused by any type of HPV.

Women aged 16-26 may have already been exposed to HPV16 or HPV18; for these women, the vaccine was less effective (about 20% at four years, but more as time went on).

I hear a new vaccine is coming soon. What's different about it?

Merck's v503 targets nine strains of HPV (HPV-16, 18, 31, 33, 45, 52, 58, 6, and 11) -- the ones that cause about 90% of cervical cancer, higher than the 70% of the current vaccine.

It has completed stage 3 clinical trials, and Merck has applied for FDA approval. It was discussed at the February 2014 meeting of the CDC's ACIP (see slides). The FDA might vote in early 2015 on whether to approve it. After that, it will take the ACIP a few months to issue recommendations, and up to two years for health plans to cover it.

Is there any point to getting vaccinated after you have been treated for an abnormal Pap?

Yes.

Vaccination after LEEP procedures has been reported to cut the risk of reinfection by about half. See "Is vaccination with quadrivalent HPV vaccine after loop electrosurgical excision procedure effective in preventing recurrence in patients with high-grade cervical intraepithelial neoplasia (CIN2-3)?" and "Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data".

Has diet or nutrition been shown to lower the incidence of cervical cancer?

Not yet, but there are hints that frequent consumtion of some fruits and vegetables may help the body fight off an HPV infection.

One team found that, among HPV-positive women, those with abnormal pap smears and those with persistent HPV infections were less likely to eat papaya or oranges every week than those without.

Another study found that, among HPV positive women, those who cleared their HPV infections were more likely to eat vegetables every day than those who didn't.

Will new kinds of HPV viruses spring up to replace those wiped out by the vaccine?

Potentially, but we haven't seen that for sure yet.

"Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis" found only slight protection for HPV types not targeted by either vaccine, so one would not expect current vaccines to have much impact on high risk strains beyond HPV-16 and 18.

This seems to be borne out by two studies of what has happened to the prevalence of HPV types after the introduction of national vaccination programs.

In England, after two to four years of national Cervarix vaccination, among a representative sample of 16-18 year old sexually active girls (65% of whom had been fully vaccinated), HPV-16 and 18 declined by about two thirds, other high-risk types as a whole were roughly unchanged, and HPV-6 and 11 increased by about a third.

In the United States, after zero to four years of national Gardasil vaccination, among a representative sample of 14-19 year old sexually active girls (about 32% of which had been fully vaccinated), HPV-16, 18, 6, and 11 declined by about half, and there were no other significant changes.

"Vaccine-type human papillomavirus and evidence of herd protection after vaccine introduction" reported

the prevalence of high-risk, nonvaccine-type HPV increased 7.6% (48.6%-56.2%, P = .0038) for all participants, and the increase was significant (13.6%, P < .0001) for vaccinated but not for unvaccinated participants... A possible explanation for the finding that nonvaccine-type HPV prevalence increased in vaccinated but not in unvaccinated young women is that their risk for HPV may differ. Vaccinated versus unvaccinated girls did not differ in number of recent and lifetime sexual partners; however, they were more likely to be African American (84% vs 54%, P < .0001) and reported, on average, an earlier age of first sexual intercourse (mean = 14.6 vs 15.3 years, P = .0007), both of which have been associated with higher rates of HPV infection."

Vaccines covering more types of HPV are currently under develoment. In particular, a nonavalent vaccine is near approval.

Further out, vaccines based on chimeric L1/L2 protein combinations (pubmed 23752042), L2 proteins alone, or L2-flagellin combinations may offer even wider coverage in the future.

Does the vaccine work for African American women?

Yes. It's probably safe to say that the vaccine prevents the strains of HPV that cause 60% or more of cervical cancer, regardless of ethnicity. The exact number does vary by region and ethnic group between about 60% and 75%.

Some HPV types that cause abnormal pap results (e.g. CIN2) but seldom progress to cancer are more common in African American women. That may mean that vaccinated African American women are somewhat more likely than their white peers to have an abnormal pap result, but not much more likely to have cervical cancer.

According to "Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis update",

Combined HPV16/18 prevalence among ICC cases was slightly higher in Europe, North America and Australia (74-77%) than in Africa, Asia and South/Central America (65-70%). The next most common HPV types were the same in each continent, namely HPV31, 33, 35, 45, 52 and 58...
By that estimate, the current vaccine should prevent about 75% of cervical cancer in North America, and about 67% of cervical cancer in South America.

Not coincidentally, the upcoming nonavalent (nine-strain) HPV vaccine adds protection for types 31, 33, 45, 52, 58, and will prevent the strains that cause about 90% of cervical cancer worldwide.

"Human papillomavirus genotypes in high-grade cervical lesions in the United States" found

"Among 4,121 CIN2+ cases reported during 2008-2009 in 18- to 39-year-old women ... Compared to non-Hispanic whites, HPV 35 and 58 were significantly more common in non-Hispanic blacks (14.5% vs 4.2%; 12.3% vs 3.4%) ... For CIN3, HPV 16 or 18 was present in 71.4% of specimens from non-Hispanic whites compared with 50.4% in non-Hispanic blacks and 54.6% in Hispanics...

However, even if true, these results do not necessarily imply differential effectiveness of vaccine for the prevention of cervical cancer. Among oncogenic HPV types, vaccine type 16 has a higher potential to persist and cause cancer than most other types [25-27], and although not a direct measure of risk, data from the Guan et al study [24] corroborate the relative importance of HPV 16 and 18 for causing cervical cancer, even in regions where lower proportions of these types were found in high-grade lesions... "

A recent study by C Hoya et al claimed an even larger racial disparity for CIN2 lesions, but its results were based on a small sample size, only just barely reached statistical significance, and as the authors themselves said, may have been due to chance.

The story for disparities in throat cancer is somewhat different. " Human Papillomavirus Prevalence in Oropharyngeal Cancer before Vaccine Introduction, United States" says in Table 2 that in whites, 278 of 310 hrHPV-positive throat cancers were HPV16/18 positive, but in blacks, only 22 of 36 (or 61%) were. (So the HPV strains in throat cancer in blacks seem to be similar to that in cervical cancer, but in whites, it's tilted more towards HPV16/18 than it is in cervical cancer.)

See also the CDC's page on cancer health disparities.

Some people say that the government is paying compensation to people injured by the HPV vaccine!

In 1988, a fund was set up to compensate people injured by vaccines. If you suffered an injury listed in the Vaccine Injury Table, you have a good chance of being compensated. (No injuries related to HPV vaccines are currently in the table.) If your claimed injury isn't in the table, but you are still able to convince the judge that the injury might plausibly have been caused by the vaccine, you might still get compensated. (Hint: don't sue without an expert opinion, and if they offer a settlement, take it.) The standard of proof is plausibility, so getting compensated doesn't mean the court has ruled your injury was caused by the vaccine, just that it might have been.

As of October 2014, 73 cases have been compensated, and 85 have been dismissed without compensation.

Here are the cases I've tallied so far where the court's opinion has been made public for cases involving just the HPV vaccine:

And the tally by reported injury:
InjuryCompensatedDenied
cfs 10
death 01
fainting 10
gbs 12
hodgkin's 01
ji arthritis02
lupus 01
m. gravis 01
migraine 01
neuro prob 10
numbness 01
pancreatatis10
purpura 10
seizure 01
shingles 01
stroke 01

Some people say that there's no evidence HPV vaccines can prevent cancer better than screening.

Short answer: Vaccination and cervical cancer screening together are more effective than either by themselves. The vaccine can also prevent other kinds of cancer (e.g. anus, throat, vulva) which are on the rise. And it can protect age groups not usually screened.

Long answer:

"Introducing HPV vaccine and scaling up screening procedures to prevent deaths from cervical cancer in Japan: a cost-effectiveness analysis" (full text) estimated that vaccination and screening together reduced the lifetime risk of cancer to about half that of screening alone.

"Beyond cervical cancer: burden of other HPV-related cancers among men and women" said

In the United States annually (1998-2003), up to ... 4,753 noncervical cancers among men, and 4,128 noncervical cancers among women are potentially attributable to HPV infection. ... incidence rates for anal, oropharyngeal, and vulvar cancers have increased substantially in recent years.
The vaccine has been reported to be effective against early stages of anal and vulvar cancer.

"Effectiveness of cervical screening with age: population based case-control study of prospectively recorded data" says

Cervical screening in women aged 20-24 has little or no impact on rates of invasive cervical cancer up to age 30.
Accordingly, the UK does not screen women under 25 for cervical cancer. But a few women under that age do die of cervical cancer, and vaccination can prevent many of those deaths.

Are we overloading children's immune systems with too many vaccines?

No. "Addressing Parents' Concerns: Do Multiple Vaccines Overwhelm or Weaken the Infant's Immune System?" says
"Current studies do not support the hypothesis that multiple vaccines overwhelm, weaken, or "use up" the immune system. On the contrary, young infants have an enormous capacity to respond to multiple vaccines, as well as to the many other challenges present in the environment. By providing protection against a number of bacterial and viral pathogens, vaccines prevent the "weakening" of the immune system and consequent secondary bacterial infections occasionally caused by natural infection."

Some people say the risk of serious adverse effects from the vaccine is about the same as the risk of cancer!

Short story: The reporting rate for Gardasil for serious adverse reactions is about 230 times lower than the lifetime risk of developing cervical cancer. For death from vaccination vs. death from cervical cancer, it's about 2300 times lower.

Long story: "Postlicensure Vaccine Safety Monitoring, 2006-2013 - United States" said

From June 2006 through March 2013, approximately 56 million doses of HPV4 were distributed in the United States... During June 2006-March 2013, the Vaccine Adverse Event Reporting System (VAERS) received a total of 21,194 adverse event reports occurring in females after receipt of HPV4; 92.1% were classified as nonserious. ... during the last 7 years, reporting patterns have remained consistent with the 2009 published summary of the first 2.5 years of postlicensure reporting to VAERS.
i.e. there were 1674 serious reactions reported out of 56 million doses distributed. That's a reporting rate of serious reactions of .0029%, i.e. 3 in 100,000.

The lifetime risk of cervical cancer in the United States is about 1 in 152, or about 660 in 100,000.

So (if one trusts statistics from VAERS, which one should not do), the serious adverse reaction reporting rate from Gardasil is about 230 times lower than the lifetime risk of developing cervical cancer.

Looking at death: the reporting rate for death according to the 2009 summary was about 0.1 per 100,000. The lifetime risk of dying from cervical cancer in the United States is about 1 in 435, or about 230 in 100,000.

Again, the vaccine is safer, by a factor of 2300.

Some people say vaccinating against HPV makes girls more promiscuous and more likely to get pregnant or get VD!

This is not supported by the evidence. "Sexual activity-related outcomes after human papillomavirus vaccination of 11- to 12-year-olds" says
Previous surveys on hypothesized sexual activity changes after human papillomavirus (HPV) vaccination may be subject to self-response biases. To date, no studies measured clinical markers of sexual activity after HPV vaccination. This study evaluated sexual activity-related clinical outcomes after adolescent vaccination. ... Conclusions: HPV vaccination in the recommended ages was not associated with increased sexual activity-related outcome rates.
Two other studies, "Human Papillomavirus Vaccine Increases High-Risk Sexual Behaviors: A Myth or Valid Concern" and "Human papillomavirus (HPV) vaccination and subsequent sexual behaviour: Evidence from a large survey of Nordic women" also found no evidence of sexual practices differing between vaccinated and non-vaccinated women.

Some people say Gardasil sent a bunch of girls in some town to the hospital!

In 2011, 12 girls in Le Roy, New York came down with strange symptoms some blamed on the HPV vaccine. An investigation found that only seven of the twelve girls actually had the vaccine, that three already had symptoms before vaccination, and that the symptoms were the result of ' conversion disorder'. The girls were treated separately, and as of 2013, most are doing well.

In May 2014, girls in Carmen de Bolaivar in Columbia started fainting, and by September, the media was full of reports blaming the HPV vaccine. But the Minister of Health tweeted the results of a preliminary investigation which found

"... symptoms were also present in non-vaccinated girls"
So it is likely that the Columbian girls were also suffering from conversion disorder. More news as it happens :-)

Some people say Gardasil killed a schoolgirl!

In 2009, a British schoolgirl died shortly after immunization. In 2014, a Milwaukee schoolgirl died a few hours after being vaccinated.

Both cases received quite a bit of media attention, and there was much speculation that the HPV vaccine might have been to blame. However, their autopsies showed that the British girl was killed by a pre-existing chest tumor, and the Milwaukee girl was killed by an overdose of benadryl. In neither case does the HPV vaccine appear to have been at fault.

The CDC says that as of March 2014, of the 96 reports of death received by VAERS, 47 reports had enough information to investigate, but none of them appeared to be caused by the vaccine. By contrast, the human papilloma virus kills about one person every 82 minutes in the United States. (You can read a few of their stories here.)

For more data, see HPV vaccine safety.

Some people say Gardasil causes seizures!

Yes, but only rarely, and normally without any harm. There are several ways this might happen.

Fainting ("syncope") can occur especially during the first 15 minutes after any shot. You can hurt yourself if you fall when fainting; that's why everyone getting any shot should remain seated for 15 minutes afterwards.

Fainting can also be associated with seizures; a study of syncope and seizures after HPV vaccination found

"The reporting rate after 4vHPV vaccine for syncope and syncopal seizures was 7.8/100,000 and 2.6/100,000 doses distributed, respectively."

Seizures can also be triggered by the brief fever that sometimes follows immunization. According to "Childhood Febrile Seizures: Overview and Implications",

"Although the occurrence of febrile seizures in childhood is quite common, they can be extremely frightening, emotionally traumatic and anxiety provoking when witnessed by parents. During the seizure, the parent may perceive that their child is dying, but fortunately the vast majority of febrile seizures are benign."

Finally, there are seizures caused by genetic defects. A study of 23 children who developed epilepsy after vaccination identified underlying genetic causes in 65% of cases.

Some people say Gardasil caused some girls to go sterile!

They're referring to "Premature ovarian failure 3 years after menarche in a 16-year-old girl following human papillomavirus vaccination" and "Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus Vaccination: A Case Series Seen in General Practice" by Dr. D. Little and H. Ward, and/or "Human Papilloma Virus Vaccine and Primary Ovarian Failure: Another Facet of the Autoimmune/Inflammatory Syndrome Induced by Adjuvants" by S Colafrancesco, Lucija Tomljenovic et al.

There are several problems with the papers by Little and Ward.

First: the authors have an axe to grind. They are pro-life activists; Dr. Little serves on the board of advisors of Family Life International, a Catholic group which claimed as in 2007 (and still claims today) that the vaccine promotes promiscuity and VD, which is not supported by the evidence. This should have been disclosed as a conflict of interest.

Second, the paper claims to have ruled out all causes other than Gardasil for the problem... but they didn't check (as far as I know) for the specific mutations estimated to account for 20%-25% of the risk for premature ovarian failure.

Third, premature ovarian failure happens in unvaccinated girls at a significant rate -- about one in ten thousand girls per year from age 15 up. If there are about 6 million 16 year old girls in the US, that paper predicts roughly 600 cases of premature ovarian failue per year among them -- with or without vaccination. So hearing about two or three girls with premature ovarian failure is not a sign of trouble; hearing about ten thousand might be.

Fourth, the latter paper cites an experiment in rats (see below) that gave the equivalent of about 400,000 doses of Gardasil to a single rat at the equivalent age of a human one-year-old to claim that an ingredient in Gardasil causes sterility in rats. That's a rather unrealistic comparison.

The paper by Colafrancesco and Tomljenovic has similar problems; it lists a case of two sisters with premature ovarian failure. When two sisters both come down with a genetically linked disease, it's even more likely that a bad gene is the cause, but that was not mentioned in the paper.

So these case studies don't show that Gardasil is dangerous, they don't show that the four cases were not caused by a genetic problem, and they don't account for the fact that we don't know why the majority of cases of this problem occur with or without Gardasil.

( Thanks to Respectful Insolence for posting excerpts of the second paper. )

Some people say an ingredient in Gardasil caused rats to go sterile!

Short story: giving 400,000 doses of Gardasil to a one year old baby might cause problems, but that doesn't say much about the real world.

Long story: Newborn rats injected with polysorbate 80 were found to grow up to be sterile in one experiment in 1993. The rats probably weighed 6-10 grams when injected, and the smallest amount injected was 0.1ml of 1% Polysorbate 80, about one milligram, or 10 / (0.1 x 10^-3) = 1 x 10^-3 = 0.1% of their body weight.

By comparison, 9 year old girls weigh about 20kg, and Gardasil contains 50 micrograms of Polysorbate 80, or about (50 x 10^-6)/(20 x 10^3) = 2.5 x 10^-9 = 0.0000003% of their body weight. So the smallest dose in the experiment was about 1 x 10^-3 / 2.5 x 10^-9 = 4 x 10^5 = four hundred thousand times higher than the dose given to girls by weight.

It takes rats about six weeks to mature sexually, but it takes humans about 12 years, so each rat day corresponds to roughly 100 human days when looking at ovary maturity.

The rats were injected when they were 4 rat days, or about 1 human year, old. Because this was such a high dose, given so early in life when the rats were still developing, the rat study seems to have little bearing on the safety of Gardasil in 9 year olds.

(Note: those are just quick back-of-the-envelope calculations. If anyone finds an error in the above figures, please let me know.)

Some people say that getting the vaccine if you already have HPV increases your chance of cancer!

Short story: Those people are looking at a very small study that was probably statistically unbalanced. This group had about twice as many positive pap smears as the controls. Because the vaccine doesn't protect you if you already have HPV, you would in fact expect the group that was sicker before vaccination to be sicker after vaccination. And that's just what happened. A second, larger study found no such increase in cancer after vaccination.

Long story: The Phase III trials of Gardasil enrolled thousands of healthy women, checked whether they had HPV at the start, vaccinated them, and then looked at how many of them went on to develop disease. There were two big studies: Study 13, and Study 15. Mostly they analyzed the data from women who didn't have HPV before vaccinating, but they also analyzed the data from women who very definitely had active HPV at the start of the study (about 293 women in Study 13, and 828 women in Study 15).

Because the vaccine works by preventing HPV infection, the expectation was that vaccination wouldn't have any effect on cancer rates.

Here are the results:
HPV+ Women who developed CIN 2/3 or worse by end of study / total women
PopulationGardasilPlacebo
HPV+ at start of Study 1331/15619/137
HPV+ at start of Study 1542/39848/430
In Study 15, about as many vaccinated as unvaccinated women got cancer, as expected, but in Study 13, surprisingly many vaccinated women got cancer.

When they looked closer at the data, they saw that the women who were HPV+ at start of Study 13 weren't randomized very well:
Study 013 subgroupGardasil Placebo
Current smoker at start of study34.6%31.4%
History of cervicovaginal infection or STD at start of study 35.9% 32.1%
Pap test with HSIL at start of study6.5%3.7%
Not only was the rate of positive Pap tests before vaccination among those randomized to the Gardasil group was almost twice that among those randomized to the placebo group, other risk factors were higher in the Gardasil group as well. This probably explains the surprising result from Study 13.

(See Tables 17, 18, and 20, and the conclusion on page 15, of the Phase 3 study summary.)

I heard Japan and some other countries banned Gardasil!

As far as I know, no country has banned Gardasil. Here are some countries rumored to have banned it, and the actual situation:

Japan

In June 2013, reacting to reports of adverse effects, Japan's health ministry announced that it would stop actively recommending it, pending investigation, but that the vaccine would continue to be administered free of charge. The investigation is now complete; "Summary of the Report on the Surveillance Results of HPV Vaccines" says "the available evidence was insufficient to suspend the marketing authorizations for the HPV vaccines." The Japanese government is now considering whether to resume active recommendation for HPV vaccination.

The vaccine is still recommended in Japan; see Hachinohe City Routine Immunization Schedule (Nov 2013), Vaccination Schedule Recommended by the Japan Pediatrics Society (Jan 2014), and Immunization Schedule, Japan 2014 (as of April 1, 2014)

According to "Effect on HPV vaccination in Japan resulting from news report of adverse events and suspension of governmental recommendation for HPV vaccination", vaccine initiation rates fell sharply as a result of the scare.

See also the excellent account at The HPV Vaccination in Japan -- Issues and Options (CSIS, April 2014) as well as HPV vaccination programme in Japan (Lancet, Aug 2013.)

Israel

On 3 September 2013, Israel considered cancelling their free school-based HPV vaccination program, but less than a week later, decided to go ahead with it. Also, it remains on the schedule of recommended vaccines.

India

On 4 July 2008, India's DCGI approved Gardasil for use in India. In 2009, a demonstration project was started which immunized girls in two states. Antivaccination groups protested, and in 2010, responding to public pressure after seven deaths that turned out to be unrelated to the vaccine, India suspended the demonstration project. However, the vaccine itself is still approved in India, and appears on the IAP's 2013 recommended schedule of vaccination.

France

In early 2014, antivaccine activists sent an open letter and petition charging that the vaccine was unsafe and ineffective, and Michele Rivasa (a MEP who thinks aluminum in vaccines is harmful) held a meeting on the topic. In response, 17 national societies of gynecologists, midwives, obstetricians, oncologists, and others released their own open letter and petition. There has been no change in the status of HPV vaccination in France; it still appears on the Calendrier des vaccinations 2014 dated 25 April 2014.

Some doctors in Germany say insurers are providing outdated and misleading HPV vaccine info. What's up with that?

According to Aerzte Zeitung online, Die Zeit, and a press release from the German Gynecologists Association (BVF) and the German Pediatricians Association (BVKJ), two insurers are distributing outdated patient information about the HPV vaccine.

The information gives the impression that the vaccine is risky and experimental. The BFV tried in December 2013 to get the insurers to update their info, without results, so they have now lodged a complaint with the federal office for insurance.

I checked, and the information is indeed outdated, and furthermore was based on an incorrect translation of the old ECDC information.

I heard the lead developer of Gardasil now says it's a deadly scam!!

Dr. Diane Harper, who helped test Gardasil and researches HPV prevention, was in the news in 2009, and was misquoted as being against the vaccine. In an interview to clarify her position, she said
"Duration of efficacy is key to the entire question. If duration is at least fifteen years, then vaccinating 11-year-old girls will protect them until they are 26 and will prevent some precancers, but postpone most cancers. If duration of efficacy is less than fifteen years, then no cancers are prevented, only postponed."
She then wrote an article laying out her position in detail. (That article was written back when we thought 88% of all HPV-caused cancers were cervical cancer; according to the CDC, the current figure is 45%. Also, that article assumed that HPV vaccination only reduced abnormal pap smears by 10%, but a more current figure is 47.5%.)

More recently, she wrote

"US health policy preferences push achieving a high coverage rate of young women instead of relying on possible herd immunity from both sexes of a partially vaccinated population...

A majority of adolescents appear to participate in long chain networks of relationships... Interruption by HPV vaccination may reduce this spanning network into smaller isolated groups, thereby preventing a majority of HPV infections... young men are responsible for infection propagation twice as often as young women[5]. Perhaps... to see a more cost-effective reduction in HPV infections, we should turn our attention to targeting boys before high school entry."

On January 5th, 2013, I had the following email conversation with her:
From: Dan Kegel
To: Diane Harper

Hi Dr. Harper,
recently on TV you said
"I looked at the fact that Gardasil doesn't last long enough to
prevent cervical cancer..."
...
I think you meant to say "We don't know yet whether Gardasil lasts
long enough to prevent cervical cancer without a booster shot", right?

From: Diane Harper
To: Dan Kegel

...
you are correct, I should be quoted as saying

"We don't know yet whether Gardasil lasts
long enough to prevent cervical cancer without a booster shot", 

So I do give you permission to print that in your blog!
In other words: she is a (very) cautious advocate for the vaccine, and has never said it should not be used.


See also:

Other HPV FAQ pages

Related pages


Corrections and suggestions welcome, please send them to dank at kegel com.

Copyright 2013, 2014 Dan Kegel
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