What is HPV?

HPV stands for Human Papilloma Virus. HPV infections usually go away on their own with no symptoms... but if the infection persists for several years, symptoms such as warts or cancer may develop.

What diseases can HPV cause?

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

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 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?

Original 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.

Current Gardasil prevents nine strains of HPV (HPV-16, 18, 31, 33, 45, 52, 58, 6, and 11) -- the ones that cause about 90% 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.

"Racial and ethnic disparities in human papillomavirus (HPV)-associated cancer burden with first- and second-generation HPV vaccines" estimated the lifetime risk of all HPV-caused cancers as about 1.4% (or 1 in 71) for women, and 0.9% (or 1 in 110) for men, in the US.

The lifetime risk of cervical cancer is 1 in 161 in the United States. It is higher in countries without widespread screening programs; for instance, it is 1 in 40 in South Africa. See hpvcentre.net for up to date statistics for each country; their fact sheets give the cumulative risk of cervical cancer (which you can convert to lifetime risk by dividing into 100%).

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

How does HPV cause cancer?

HPV carcinogenesis is complex.

It appears that the crucial gene for HPV16 carcinogenesis is E7, as it has been found to be highly conserved in precancers and cancers.

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?


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. It then extended the approved age to 45 in 2018.

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?

At or after age 15: 3 doses. The first two doses should be 1-2 months apart; the third dose should be at least 6 months after the second.

Before age 15: 2 doses 6 to 12 months apart.

Evidence for recommending fewer doses in younger adolescents came from a 2013 study which found omitting the middle dose produced sufficent antibody levels in girls age 9-13.
Evidence for waiting six months between doses came from a 2015 study which found a 6 month interval was 63% more effective than a 2 month interval.

Who should be vaccinated?

In the US, HPV vaccination is approved for ages 9-45, and recommended for routine use at ages 11-13. In Australia, it is also approved for women up to age 45.

It is also recommended at other ages in special situations, e.g. after receiving a bone marrow or stem cell transplant, before receiving an organ transplant, or in other immunocompromised people.

Research is ongoing to see if it is effective in other situations, e.g. to accompany other treatment for active clinical disease caused by HPV.

Effectiveness decreases with age simply because the longer you've been around, the more likely you already have a persistent HPV infection. Thus if you're above the usual age of vaccination, insurance may not cover it, and you may need to pay for the vaccine yourself.

"Effectiveness of catch-up human papillomavirus vaccination on incident cervical neoplasia in a US health-care setting: a population-based case-control study" found a three-dose catch-up vaccination was effective against CIN2+ and CIN3+ when the first dose was given as late as age 20, but not for women aged 21 and older at first dose.

(See also "HPV vaccine over age 26 -- is it worth it?")

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.

Gardasil should not be given to people with a history of immediate hypersensitivity to yeast, see the ACIP recommendations.

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%-85% 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 ten years, probably longer.

Four studies have checked Gardasil's protection at six, eight, nine, ten, and 10 - 12 years, respectively; each study found Gardasil was still protecting.

The newer but very similar Gardasil 9 vaccine has been shown to protect at least six years so far, and a single booster shot produces a strong immune memory response.

Studies have checked Cervarix's protection at 6, 9.4, 10, and 10 years, found no new persistent HPV 16/18 infections in vaccinated women during that time, and estaimated that vaccinating before age 25 gives lifelong protection against HPV 16 and 18.

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 the CDC's "HPV Vaccine Q&A" says "If protection from HPV vaccine doesn't last as long as it should, then the Advisory Committee for Immunization Practice would review the data and determine if a booster should be recommended."

Studies have found HPV vaccines work as a booster at 4, 5, 5, 6, 7, and 8.5 years after original vaccination, even if the booster is a different vaccine than the original.

See also "Long-Term Studies of Quadrivalent HPV (qHPV) Vaccine Effectiveness", "The Efficacy and Duration of Vaccine Protection Against Human Papillomavirus - A Systematic Review and Meta-analysis", and "Review of Data on Duration of Protection after HPV Vaccination, Advisory Committee on Immunization Practices, June 23, 2016"

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

"Estimating the number needed to vaccinate to prevent diseases and death related to human papillomavirus infection" said
"Among 12-year-old girls, we estimated that the number needed to vaccinate to prevent an episode of genital warts would be 8 (80% credibility interval [CrI] 5-15) and a case of cervical cancer 324 (80% CrI 195-757)."
"The Impact of HPV Catch-Up Vaccination in Australia: Implications for Introduction of Multiple Age Cohort Vaccination and Postvaccination Data Interpretation" said
"the number needed to vaccinate to prevent 1 anogential warts (AGW) case or cervical cancer (CC) was similar for routine + catch-up (AGW = 9.9, CC = 678) and routine-only vaccination (AGW = 9.9, CC = 677)"
Since ~2/3 of hpv-caused cancer is noncervical, NNT to prevent any cancer is probably under 300. (Citation needed)

Do condoms prevent HPV infections?

Maybe, but only if used every time, and even that's not quite clear.

"Condom use in prevention of HPV infections and cervical neoplasia: systematic review of longitudinal studies" found

Four out of eight longitudinal studies showed a statistically significant protective effect of condoms in prevention of HPV infections and cervical neoplasia"
i.e. half of all studies did not find condoms provided significant protection against HPV.

For illustration, here are two studies that did find some protection:

"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.

"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.

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.

And vaccinating by age 13 is even more effective.

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?

"The impact and cost-effectiveness of nonavalent HPV vaccination in the United States: Estimates from a simplified transmission model (2016) said
"Compared with a vaccination program of 4vHPV for both sexes, a vaccination program of 9vHPV for both sexes can improve health outcomes and can be cost-saving."
"Comparison of two dose and three dose human papillomavirus vaccine schedules: cost effectiveness analysis based on transmission model" (2015) said
"Giving at least two doses of vaccine seems to be highly cost effective across the entire range of scenarios considered."

"Modeling cervical cancer prevention in developed countries" (2008) 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


Has the vaccine already begun lowering the prevalence of HPV infections?

Yes, age groups which were well vaccinated on time have strikingly lower rates of infection.

The impressive fall in Australia in women ages 25-35 is due to that country's extensive catch-up vaccination program; see "The Impact of HPV Catch-Up Vaccination in Australia: Implications for Introduction of Multiple Age Cohort Vaccination and Postvaccination Data Interpretation".

"Substantial decline in prevalence of vaccine-type and non-vaccine type HPV in vaccinated and unvaccinated girls 5 years after implementing HPV vaccine in Norway" (2018) found

"A 42% (95% CI 37%-47%) reduction in any HPV type and 81% (95% CI 76%-85%) reduction in vaccine types (6/11/16/18) was observed in the vaccine-eligible cohort compared to the 1994-cohort. Vaccine types were reduced by 54% (95% CI 39%-66%) in unvaccinated and 90% (95% CI 86%-92%) in vaccinated 1997-girls, when compared to unvaccinated 1994-girls."

"The Impact of the National HPV Vaccination Program in England Using the Bivalent HPV Vaccine: Surveillance of Type-Specific HPV in Young Females, 2010-2016 (2018) found

"Prevalence of HPV16/18 decreased between 2010/2011 and 2016 from 8.2% to 1.6% in 16-18 year olds and from 14.0% to 1.6% in 19-21 year olds...
Eight years after the introduction of a national HPV vaccination program, substantial declines have occurred in HPV16/18 and HPV31/33/45. The prevalence of other high-risk HPV types has not changed."
"Very low prevalence of vaccine HPV types among 18 to 35 year old Australian women, nine years following implementation of vaccination" (2018) found
"For the 2015 sample, the [Australian] National HPV Vaccination Register-confirmed three-dose coverage was 53.3% (65.0% and 40.3% among those aged 18-24 and 25-35, respectively). Prevalence of vaccine HPV types decreased from 22.7% (2005-2007) and 7.3% (2010-2012), to 1.5% (2015) (p-trend<0.001) among women aged 18-24 years, and from 11.8% (2005-2007) to 1.1% (2015) (p=0.001) among those aged 25-35 years."

"Low prevalence of vaccine-type HPV infections in young women following the implementation of a school-based and catch-up vaccination in Quebec, Canada" (2018) found

Infections with HPV types included in the vaccine are rare in women aged less than 23 years and are virtually absent in those who received at least one dose of vaccine before sexual debut.

"Prevalence of HPV After Introduction of the Vaccination Program in the United States" (2016) found


"HPV Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009-2013" (2016) found

"Positivity for HPV 16 and 18 in the samples was 11% (95% CI 9.7%-12.5%) among fully vaccinated women and 29.4% (95% CI 27.9%-30.9%) among nonvaccinated women."

Has the vaccine already begun lowering the incidence of genital warts?


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 the vaccine already begun lowering the incidence of abnormal pap smears?

Yes. Many 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, that vaccinating by age 14 gives more protection, and that vaccinating by age 13 is even better.

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 the vaccine already begun lowering the need for treating precancerous lesions?

Yes. "Reduction in colposcopy workload and associated clinical activity following human papillomavirus (HPV) catch-up vaccination programme in Scotland: an ecological study" studied 20/21 year old women who receieved colposcopies between 2008 and 2014, and found:
"Women were less likely to have diagnostic or therapeutic interventions. The proportion with no biopsy (2008/9, 19.5%; 2013/14, 26.9%; linear trend P < 0.0001) and no treatment (2008/9, 74.9%; 2013/14, 91.8%; linear trend P < 0.0001) increased over the period of observation."

Has the vaccine already begun lowering the incidence of cervical cancer?


Any decline will show up in women vaccinated on time in 2007-2008 first. Since cervical cancer takes time to develop, no noticable decline was expected before 2016 or so, and a clinical trial designed to measure it was expected to have results by 2024.

Here are the indications we have so far:

Has the vaccine already begun lowering the incidence of other diseases?

There is evidence that HPV vaccination reduces rate of at least one other disease:

"Australian national surveillance of juvenile onset recurrent respiratory papillomatosis: declining incidence post quadrivalent hpv vaccination" reported "The rate [of JORRP] declined from 0.3 per 100,000 in 2012 to 0.04 per 100,000 in 2016. Among incident cases, no mothers had been vaccinated prior to pregnancy".

Also, there are very early indications that HPV vaccination may reduce breast cancer in young women, as HPV oncogenes are known to be active in some breast cancers, and the recent paper "Vaccination protects against invasive HPV-associated cancers" also found a lower incidence of breast cancer in vaccinated women; see Table 1 above.

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 has been approved. What's different about it?

Doctors in the US mostly switched to the new vaccine, Gardasil 9, by 2016. See "Spotlight on the 9-valent HPV vaccine" and "Use of 9-Valent Human Papillomavirus (HPV) Vaccine: Updated HPV Vaccination Recommendations of the Advisory Committee on Immunization Practices".

The new vaccine 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.

In clinical trials, it reduced biopsies for and treatments for cervical abnormalities from HPV 31/33/45/52/58 by 97% and 87%, respectively (see page 21 of the ACIP presentation).

It was approved by the FDA in December 2014, and recommended by the CDC in February 2015.

Are there even better vaccines on the horizon?

Yes, but they won't be ready for many years.

The current vaccines are based on the L1 major capsid protein, which is different for each strain. One promising one is based on the L2 minor capsid protein, which is much less variable. See for example "VLPs Displaying a Single L2 Epitope Induce Broadly Cross-Neutralizing Antibodies against HPV", "A Universal Virus-Like Particle-based Vaccine for HPV: Longevity of Protection and Role of Endogenous and Exogenous Adjuvants", and "Efficacy of RG1-VLP Vaccination against Infections with Genital and Cutaneous Human Papillomaviruses".

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


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 high-risk HPV viruses replace those wiped out by the vaccine?

HPV types not targeted by the vaccine will likely continue their previous slow increase, especially in the unvaccinated population.

But since current vaccine targets most of the high-risk strains, generally the increase will be in low-risk strains that don't cause cancer.

And that's exactly what we're seeing; the vaccine continues to be very effective at preventing high-risk HPV infections.

See for instance:

That said, in ten or so years, a broader spectrum vaccine will likely become available, perhaps based on L2 or E7 antigens. (See Google Scholar search for hpv broad spectrum vaccine.)

Does the vaccine work for women of all ethnicities?

The current 9-strain vaccine does work roughly equally well for all ethnic groups.

The original 4-strain vaccine protected blacks about 20% less well against cervical cancer, but the disparity largely goes away with current vaccines.

A large recent study by S.Hariri et al (full text) measured which types of HPV were involved in cervical cancer vs. race. Here's its key finding (Figure 4b):

Dark is original vax (Gardasil), grey is added types in current vax (Gardasil 9).
This shows that the current vaccine covers HPV types that cause about 80-90% of CIN3 in blacks, and about 90% in whites.

See also:

Some people say Danish girls are suffering from POTS because of the vaccine!

After a Danish doctor published a paper claiming that many vaccinated girls suffered from POTS, Danish government asked the EU to look into the vaccine's safety. The EU's Pharmacovigilance Risk Assessment Committee investigated; their report concluded

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. 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 July 2015, 80 cases have been compensated, and 82 have been dismissed without compensation.

Here's a table of cases where a case involving just the HPV vaccine was either settled or won.

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.


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" (2012) studied 493 vaccinated and 905 unvaccinated girls, and said:
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.
See also

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 Bolivar 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. See also "HPV vaccine confidence and cases of mass psychogenic illness following immunization in Carmen de Bolivar, Colombia".

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


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.

HPV and fertility

HPV infections may cause fertility problems. See e.g. The review "Primary Ovarian Insufficiency and Human Papilloma Virus Vaccines: A Review of the Current Evidence" concluded
Current evidence is insufficient to suggest or to support a causal relationship between human papilloma virus vaccination and primary ovarian insufficiency.
The study "Primary Ovarian Insufficiency and Adolescent Vaccination" (see also presentation) looked at one type of fertility problem, POI, and found
"From a cohort of 199,078 female patients, we identified 120 with diagnoses suggestive of POI. After adjudication and exclusion of 26 POI cases with known causes, we confirmed 46 idiopathic POI cases. POI incidence was low in 11- to 14-year-olds (0.87 per 1,000,000 person-months) and increased with age. One confirmed case patient received the HPV vaccine 23 months before the first clinical evaluation for delayed menarche. The adjusted hazard ratio [of POI] was 0.30 (95% CI: 0.07-1.36) after HPV, 0.88 (95% CI: 0.37-2.10) after Tdap, 1.42 (95% CI: 0.59-3.41) after II, and 0.94 (95% CI: 0.27-3.23) after MenACWY vaccination.

We did not find a statistically significant elevated risk of POI after HPV, Tdap, II, or MenACWY vaccination in this population-based retrospective cohort study. These findings should lessen concern about POI risk after adolescent vaccination."

Oddly, though, rumors to the contrary circulate from time to time. For editorial discussions of the rumors, see e.g.:

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

No, Gardasil does not cause sterility in rats, even when given the full human dose. See "Lack of effects on fertility and developmental toxicity of a quadrivalent HPV vaccine in Sprague-Dawley rats" and "Lack of effects on male fertility from a quadrivalent HPV vaccine in Sprague-Dawley rats".

If you give newborn rats 0.1% of their body weight of one of the ingredients of Gardasil (see Newborn rats injected with polysorbate 80) there are problems, but that's about four hundred thousand times higher than the human dose by weight.

Some people say there was no trial of Gardasil against a real placebo!

Most trials were against a placebo that was the same as the vaccine, but lacked the key ingredient, the L1 protein from HPV. That's exactly how you want to test for effectiveness, and for problems unique to this vaccine.

For problems common to all vaccines, you might want to test against a simpler placebo. One trial's placebo also omitted the aluminum adjuvant: "Safety and persistent immunogenicity of a quadrivalent human papillomavirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents: a randomized controlled trial." (alternate link) compared adverse events in Gardasil vs. a simpler placebo for 18 months after vaccination. (In all, 275 girls and 322 boys received the saline placebo.) It concluded "No serious vaccine-related adverse experiences were reported."

The clinical trial "Safety and immunogenicity of a 9-valent HPV vaccine in females 12-26 years of age who previously received the quadrivalent HPV vaccine." compared adverse events in Gardasil 9 vs. a saline placebo for 15 days post vaccination.

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


This rumor is a distortion of the studies required by the FDA before approving Gardasil.

Two big studies (Protocol 13, and Protocol 15) mostly looked at women who didn't have HPV before vaccinating, but they also looked at a few women who had active HPV infections at the start of the study (about 293 women in Protocol 13, and 828 women in Protocol 15).

Because the vaccine works by preventing HPV infection, the expectation was that vaccination wouldn't have any effect on cancer rates on these hpv-positive women. And that's exactly what they found in Protocol 15.

But in Protocol 13, it turned out that the HPV positive women were twice as likely to already have HSIL at the start of the test, before vaccination (6.5% vs. 3.7%). And not surprisingly, these women went on to have more cancer.

When you start with more precancer, you get more cancer, regardless of whether you later vaccinate.

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

See also Does HPV vaccination increase cancer risk in carriers? at ask.metafilter.com

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:


As of June 2012, Japan reported 75 serious reactions in 6,338,709 vaccinations with Cervarix, and 7 serious reactions in 530,826 vaccinations with Gardasil.. That's about 1 in 100,000.

In June 2013, reacting to a burst of reports of adverse effects in the media (reportedly including a sensationalist presentation with faked mouse data, see Dr. Riko Muranaka's acceptance speech for the John Maddox prize), 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 Japan Society of Obstetrics and Gynecology demanded in August 2015 that the recommendation be resumed, and again in January 2017, but as of October 2018, it's still not being actively promoted.

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.

A 2017 survey of Japanese gynecologists and obstetricians found 70%-80% currently held positive opinions of the safety and efficacy of the HPV vaccine.

See also the excellent account at HPV Vaccination in Japan -- The Continuing Debate and Global Impacts (CSIS, April 2015; an update of The HPV Vaccination in Japan -- Issues and Options), as well as "HPV Vaccination Controversy in Japan, Rates Plummet to 1%" (July 2016) and "HPV vaccination programme in Japan" (Lancet, Aug 2013.)

The vaccine is still on the immunization calendar in Japan; see Vaccination Schedule Recommended by the Japan Pediatrics Society (October 2016), inoculation possible vaccine in Japan type (May 18, 2015) (japanese), Immunization Schedule, Japan 2014 (as of April 1, 2014), and Hachinohe City Routine Immunization Schedule (Nov 2013).

See also "No Association between HPV Vaccine and Reported Post-Vaccination Symptoms in Japanese Young Women: Results of the Nagoya Study".


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. In September 2015, it was announced that boys will also receive the HPV vaccine in schools.

The HPV vaccine remains on the schedule of recommended vaccines.


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. (See also the excellent account, Trial and Error: India's complicated history with cervical cancer".) The vaccine itself is still approved in India, and appears on the IAP's recommended schedule of vaccination as of 2018.

In 2016, several regions in India began routine immunization against HPV, and in 2018, the NTAGI recommended it for inclusion in the national immunization program.


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.


The HPV vaccine appears both on the Immunisation schedule of the Spanish Association of Paediatrics: 2015 Recommendations and official state vaccination calendars for 2015.

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."

and in April 2017, she wrote
"This series of vaccinations is highly likely to protect her from HPV infection until she enters the routine screening program... HPV vaccines reduce abnormal screening tests, colposcopies and excisions."
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:

How many antibodies does it take to prevent HPV infections?

Neutralization of Human Papillomavirus with Monoclonal Antibodies Reveals Different Mechanisms of Inhibition (see Fig 1B) shows how well several different monoclonal antibodies inhibit infection as a function of concentration. The best antibody, V5, was able to completely neutralize the virus at a concentration of about 10 picomoles per liter.

Neutralization of Bovine Papillomavirus by Antibodies to Li and L2 Capsid Proteins (see the other Fig 1B) studied a closely related virus, and found that about 14 molecules of one antibody, 5B6, per virus particle were enough to reduce infections by 50%; 27 (10e4 / 360) of any of the four antibodies studied per virion were enough to neutralize them completely.

Where do the antibodies come from, and how many are there?

The body can make a truly vast number of antibodies; see e.g. A Billion Antibodies, The Generation of Antibody Diversity, and The Generation of Diversity in Immunoglobulins.

Here's my poor summary of the process: Each B cell inherits genes for about 320 different light chains and about 11,000 heavy chains. It picks one of each, and uses the same pair from then on for all the antibodies it makes. There are about a million different usable combinations... but it's just a starting point; the B cell also rearranges and mutates the genes so much that thousands of different antibodies can be made from each of those million combinations. The young B cell takes its unique antibody, puts a bunch of them on its surface, and waits. When it notices that an antigen matches its antibody, it proliferates, mutating as it goes; the daughters that recognize the antigen better proliferate more. The process is a form of rapid directed evolution.

Some of the daughters mature into "plasma cells", which per nobelprize.org "produce antibodies at an amazing rate and can release tens of thousands of antibodies per second."

Other HPV FAQ pages

In alphabetical order by URL :-)

Related pages

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

Copyright 2013, 2014, 2015, 2016, 2017, 2018, 2019, 2020 Dan Kegel
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