HPV TEST: A NOVEL TECHNIQUE TO PREVENT CERVICAL CANCER

You have probably heard the term Pap test and know that you should be getting it regularly. Pap tests are important because they allow us to detect abnormalities in the uterine cervix before they turn into cancer. Thus, Pap tests have saved millions of women’s lives for more than 70 years now.

Nevertheless, as valuable as this test has been for so many years, new technology has come to improve even further our ability to find pre-cancer or early cancer of the cervix. This novel exam is called the HPV test.

In this article you will find all the information you need to know regarding this new technique, which is becoming a routine exam in most countries.

Background

  • Cervical cancer is the second-most-common cancer affecting women worldwide. It is a type of cancer that can easily be prevented, as its cause is known: the human papillomavirus (HPV, read more here).
  • Not all types of HPV are responsible for the development of cancer of the uterine cervix. Approximately 15 types of HPV are related to cancer, these are known as high-risk types or oncogenic viruses.
  • While most HPV infections resolve without treatment, infections with high-risk HPV strains that persist over time can cause precancerous changes in the cervix.
  • Precancerous conditions are not cancer, but if these abnormal changes are not treated, they may become cervical cancer. It may take 10 years or more for precancerous conditions to turn into cancer, but eventually this happens within a shorter time period.
  • Pre-cancer lesions of the cervix do not cause any symptoms. Symptoms only appear in advanced cancer. That is why all healthy women should undergo preventive exams.
  • The mainstay of cervical cancer screening for the last 70 years has been the Pap test (also called Pap smear or Test Papanicolaou). During the procedure, cells from the cervix are gently scraped away with a brush and then examined for abnormal growth, usually called cervical dysplasia,  CIN (cervical intraepithelial neoplasia), or SIL (squamous intraepithelial lesions).
  • More recently, newer technologies have become available to test for the cancer-causing types of HPV and determine if you may be at risk. This test is called the HPV test.

What is the HPV test?

  • The human papillomavirus (HPV) test detects the presence of the types of HPV virus that can lead to the development of cervical cancer.
  • The HPV test is available only to women. Although men can be infected with HPV and pass the virus along to their sex partners, no HPV test yet exists to detect the virus in men.

Why test for HPV?

  • The Pap test is a simple test that has saved uncountable women lives. However, it is not 100% accurate. The Pap test detects certain cervical abnormalities that will never progress to cancer; on the other hand, it may miss abnormal cells even when they are there.
  • Thus, knowing whether you have a type of HPV that puts you at high risk of cervical cancer will provide valuable information on the next steps in your health care, such as follow-up monitoring, further testing, or treatment of precancerous cells.
  • Recent studies have shown that HPV testing is more effective than Pap smears at detecting precancerous lesions.
  • A Pap test plus an HPV test (called co-testing) is the most effective way to find pre-cancer or early cervical cancer in women 30 and older.

Who should do the HPV test?

The HPV test is recommended if:

  • You are age 30 or older. The HPV test may be done alone or in combination with a Pap smear.
  • Your Pap test showed atypical squamous cells of undetermined significance (ASCUS). ASCUS is a common finding in a Pap test; it may be a sign of HPV infection, although many times it is just related to benign cervical polyps, a bacterial infection, or low hormone levels (menopause).
  • You had a surgical removal of a precancerous lesions, usually 6 months after the treatment. This is called “test of cure”.

Although recommendations vary in different countries, all women aged 30 to 65 years old should have the HPV test every 3 to 5 years.

Routine use of the HPV test in women under age 30 is not recommended, nor is it very helpful. HPV spreads through sexual contact and is very common in young women. Most of the times, HPV infections clear on their own within a year or two. Since cervical changes that lead to cancer take several years — often 10 years or more, younger women are usually advised to follow a watchful waiting instead of undergoing treatment for cervical changes resulting from an HPV infection.

What are the risks of HPV testing?

Although the HPV test is very accurate, it carries (like any other test) the risk of false-positive or false-negative results.

• False-positive. This means that the test showed a high-risk HPV when you really don’t have it. A false-positive result could lead to an unnecessary follow-up procedure, such as colposcopy or biopsy, and undue anxiety over the test results.

• False-negative. A false-negative test result means you really do have an HPV infection, but the test indicates that you don’t. This might cause a delay in appropriate follow-up tests or procedures.

How should I prepare for an HPV test?

The HPV test is usually done at the same time as the Pap test. You can take these measures to make both tests as accurate as possible:

  • Avoid intercourse, douching, or using any vaginal medicines or spermicidal foams, creams or jellies for two days before the test.
  • Try not to schedule the test during your menstrual period. The test can be done, but a better sample of cells can be collected at another time in your cycle.

How is the HPV test done?

  • The HPV test, alone or in combination with the Pap test, is performed at the doctor’s office and takes only a few minutes.
  • While you lie on your back with your knees bent, your doctor will gently insert an instrument called a speculum into the vagina.
  • The speculum allows the visualisation of the cervix. Samples of the cervical cells are taken using a soft brush.
  • Usually this doesn’t hurt, sometimes it may cause a mild discomfort.
  • After the procedure, you can do your normal daily activities without any restrictions.
  • Ask your doctor about when you can expect to receive your test results.

What do the results mean?

Results from your HPV test will come back as either positive or negative.

  • Positive HPV test. This means that you have a type of high-risk HPV that is linked to cervical cancer. While most women who are infected with HPV will never develop cervical cancer, it’s a warning sign that cervical cancer could develop in the future.
  • Negative HPV test. A negative test result means that you don’t have any of the types of HPV that cause cervical cancer, and you will continue with normal monitoring.

Depending on your test results, your doctor may recommend one of the following as a next step:

  • Normal monitoring. If you’re over age 30, your HPV test is negative and your Pap test is normal, you will follow the generally recommended schedule (differences apply for each country).
  • Colposcopy. In this follow-up procedure, your doctor uses a special magnifying lens (colposcope) to more closely examine your cervix.
  • Biopsy. Done in conjunction with colposcopy, a sample of cervical cells (biopsy) is taken to be examined more closely under a microscope.
  • Removal of abnormal cervical cells. To prevent abnormal cells from developing into cancerous cells, your doctor may suggest a procedure to remove the areas of tissue that contain the abnormal cells.

The bottom line…

It is true that a visit to the gynaecologist may sound frightening. You may be too busy, and feel that you don’t have the time. You may believe that you are not at risk for cancer. While all this may be true, you should know that every sexually active woman is at risk for cervical cancer, the HPV test is a simple, painless test that takes 5 minutes to be done, and will prevent some serious issues in the long run. Have your HPV test! Five minutes of your time can save your life!

References

  1. The HPV DNA test – American Cancer Society
  2. Gynecological Cancers – Centers for Disease Control and Prevention
  3. Cervical Cancer Screening: Pap and HPV tests – National Cervical Cancer Coalition
  4. Cervical Screening – National Health System UK

Photo credits

telegraph.co.ukcmdrc.comtwitter.comerewashccg.nhs.ukeverydayhealth.comhealthxchange.sgmargaretmccartney.com

FACT OR MYTH? TRUTHS, HALF-TRUTHS AND MISCONCEPTIONS ABOUT THE BIRTH CONTROL PILL

When introduced in the 1960s, the birth control pill became a symbol of female liberation

The contraceptive pill made its appearance more than 50 years ago. Emerging during a period of social and political upheaval, it  gave women the possibility to choose how and when to have a family, and to enjoy their sexual life. Thus, it is regarded as one of the greatest scientific inventions of the 20th century and one of the utmost symbols of female liberation.

From the very beginning though, this revolutionary method of contraception has been a source of controversy: some people thought it would create “a society with unbridled sexuality likely to undermine the foundations of the family”; others feared harmful effects and the birth abnormal children.

Fifty years later, the pill remains even more controversial than before and -paradoxically enough- more and more women are “liberating” from their “liberator”: the pill’s popularity is on the decline, a trend observed in many countries. The reasons behind this shift are many, but fear of side effects seems to the most recurrent. Arguably the web and social media, with the spread of countless personal stories with dramatic headlines and numerous pill scares have influenced women’s perception on the pill’s risks. But are these fears legitimate? How dangerous is the contraceptive pill? What is true and what is false?

Let’s see what science answers to the pill’s most common assumptions…

1) The pill harms your future fertility

FALSE. All scientific evidence agrees that hormonal contraceptives do not make women sterile in the long run. Sometimes it may take three to six cycles for fertility to fully return, but within a year after going off the pill, women trying to conceive are as likely to get pregnant (80%) as those who were never on the pill. In certain cases of long-term use, there may be even increased likelihood of pregnancy within 6-12 months after discontinuing it.

Moreover, hormonal birth control may preserve fertility by offering protection against pelvic inflammatory disease, endometriosis, ectopic pregnancy, ovarian cysts, ovarian and uterine cancer (see below).

2) The pill reduces sexual desire

MOSTLY FALSE. In most cases, birth control pills don’t affect libido (sexual desire): out of 10 women taking the pill, 7  experience no change in their sex drive, 2 observe increased libido, and 1 will feel less desire.

Recently, a study provided evidence that the pill does not kill desirecontextual factors, such as the relationship with the partner, stress, fatigue, family problems, recent childbirth, have a more considerable impact on sexual drive than the type of contraception used.

3) The pill makes you fat

MOSTLY FALSE. A recent extensive review study showed no evidence that birth control pills cause weight gain in most women. Although some persons may gain some weight when they start taking it, it’s often a temporary side effect due to fluid retention, not extra fat. And, like most side effects, it usually goes away within 2 to 3 months.

A woman’s weight may fluctuate naturally due to changes in age or life circumstances. Because changes in weight are common, many times they will wrongly attribute their weight gain or loss to the use of the pill.

4) The pill increases the risk of blood clots

TRUE. From the 1960s it is known that combined contraceptives pills may increase the risk of venous thrombosis, that is, a blood clot obstructing a vein, a serious and potentially life-threatening complication. Combined contraceptives contain synthetic versions of the hormones estrogen and progesterone. It is the estrogen that is mostly associated with the formation of blood clots, but the latest years it became evident that the type of progesterone also influences the risk. Indeed, the most “modern” formulations of the combined pill – the so-called third and fourth generation – containing the synthetic progesterones gestodene, desogestrel and drospirenone are associated with higher risk of thrombosis.

The European Medicines Agency (EMA) provides the following values ​​for the incidence (frequency) of deep vein thrombosis in 100,000 women of childbearing age:

  • 5 to 10 in non-pregnant women who do not use oral contraceptives,
  • 20 for women using a second generation combination pill (containing levonorgestrel),
  • 40 among women taking third and fourth generation pill.

Factors that may increase the risk of thrombosis are smoking, high blood pressure, obesity, age over 35 years, and a family or personal history of vascular accidents.

Although these figures may look scary, they should be analyzed in perspective:

  • In absence of risk factors, the absolute risk of thrombosis is very low.
  • The mortality rate of clotting events is about 1%. Thus, the odds of dying as a result of having a clot attributable to the use of the pill would be about 2 to 4 per million women.
  • The risk remains considerably lower than that related to pregnancy and birth (estimated  1 in 1000- 2000 deliveries).
  • Indicative of this is the 1995 pill scare in the UK, when a warning was issued on the increased risk of thrombosis related to third generation pills. This led many women coming off the pill, resulting in 12,400 additional births and a 9% abortions rise in 1996.

Overall, the odds of having a thrombotic episode related to the pill are very low, in particular with combined pills containing low dose of estrogen (30 or less micrograms) and old-generation progesterone (such as levonorgestrel).

The minipill, also known as the progestin-only birth control pill, is a form of oral contraception that does not contain estrogen, and its progestin dose is lower than that in the combined formulation. Although its efficacy is slightly reduced as compared to the combined pill, the minipill does not increase the risk of venous thromboembolism or arterial thrombotic accidents (see below).

5) The pill increases the risk of heart attack and stroke

TRUE. An extensive review study looking at arterial vascular accidents attributed to the pill (myocardial infarction and ischemic stroke) showed that the overall risk of arterial thrombosis was 60% increased in women using oral contraceptive pills compared to non-users. Unlike venous thrombosis, the risk did not vary according to the type of synthetic progesterone. However, it was twice as high in women taking pills with higher doses of estrogen (the older formulations of contraceptive pills).

Therefore, the combined pill containing levonorgestrel and low dose estrogen (no more than 30 µg) is the safest oral form of hormonal contraception. The minipill may also be considered in high risk women (see above).

6) A woman should not take the pill if she smokes

TRUE.  There is some evidence that smoking may decrease the effectiveness of hormonal birth control. When taking the pill, smokers experience more frequently irregular bleeding than non-smokers; this could signal that the efficacy of the pill is lowered, but more research needs to be conducted to better understand the effect of smoking on the pill’s action.

But what we do know for sure is that smokers who take combined oral contraceptives have increased risk of venous thrombosis and heart disease (see above). This risk is higher for women that smoke more than 15 cigarettes/day, are older than 35 years old or take formulations with high estrogen levels.

If you are under 35 years old and smoke, you should be extremely careful about using the pill, and the decision to take it should be individualized considering other risk factors such as personal and familiar history of high blood pressure, high cholesterol or heart disease. Smokers aged 35 or over should not take the combined contraceptive pill.

If you smoke you may opt for the mini pill, which does not seem to increase the risk of venous thromboembolism or arterial thrombotic accidents; otherwise you should discuss with your doctor about another contraceptive method, such as the intra-uterine device (IUD).

7) The pill causes mood changes and depression

DEBATABLE. Most studies have shown no effect of the pill on depression and mood changes; some studies have even found a protective effect. In 2016, an extensive review on hormonal contraception and mood changes confirmed the existing evidence, and concluded that “… negative mood changes are infrequent and combined hormonal contraception may be prescribed with confidence”.

However, a recent publication came to challenge this assertion. Danish researchers went through the health records of more than a million women using hormonal contraception. They found that those on the combined pill were 23% more likely to be prescribed an antidepressant than those not on hormonal contraception. For those on the minipill (and on other progesterone-only methods, including the hormonal IUD), the figure rose to 34%. It increased even further, to 80% more likely, for girls 15 to 19 years old on the combined pill.

There are a few important points to consider about these results:

  • Depression is a complex condition whose cause is still poorly understood. Several factors seem to play a role: genetic, environmental, psychological and social. Therefore, it is very difficult to evaluate the link between depression and hormonal contraception.
  • The Danish study does not prove that hormones are responsible for the depression – “association” does not necessarily translate into “causation”.
  • The risk of being diagnosed with depression peaks at two to three months of contraceptive use, but then begins to fall.
  •  Even if these findings are confirmed, the number of affected women remains small: 2.2 out of 100 women who use hormonal birth control develop depression, compared to 1.7 out of 100 non-users.

In conclusion, the pill may have impact on some women’s emotions, but further research is needed to establish whether hormonal contraceptives are indeed the cause of depression and mood changes.

8) The pill is 100% reliable

FALSE. Theoretically, with perfect use, the pill is 99.7% effective at preventing unwanted pregnancy. However, there are many factors that may interfere with the pill’s level of effectiveness: forgetting to take it, not taking it as directed, certain medications or medical problems…Therefore, when it comes to real life, the pill is about 92% effective: about 8 in 100 women using the combined pill will get pregnant in a year.

In any case, the birth control pill remains one of the most reliable contraceptive methods.

9) If you take the pill you don’t need the condom

FALSE. A survey conducted in France showed that “…one in ten young women 15 to 20 years old is not aware that the pill does not protect against HIV and sexually transmitted infections (STI)”. As stated before, the pill is a very good at preventing unwanted pregnancy but it offers no STI protection at all. In fact, the only contraceptive method that protects against sexually transmitted infections is the condom. Read more here.

10) The pill causes cancer

TRUE AND FALSE. The pill seems to increase the risk of certain cancers, but it protects again others. Overall, with the use of oral contraceptives the risk of endometrial and ovarian cancer is reduced, whereas the risk of breast and cervical cancer appears to be increased.

The protective effect on ovarian and endometrial cancer (the lining of the uterus) has been consistently demonstrated in many studies. This effect increases with the length of time oral contraceptives are used and continues for many years after a woman stops using the pill.

Long-term use of oral contraceptives is associated with an increased risk of cervical cancer. This correlation is not completely understood, as virtually all cervical cancers are caused by certain types of human papillomavirus (HPV). It has been suggested that women who use the pill may be less likely to use condoms, therefore increasing their risk of being exposed to HPV.

An extensive analysis of more than 70 studies suggested an increased risk of breast cancer among current and recent users of hormonal contraception. The risk was highest for women who started using oral contraceptives as teenagers. However, by 10 years after cessation of use, their risk was similar to that in women who had never used it.

Since most studies so far have evaluated birth control pill older formulations with higher doses of hormones, until recently it was assumed that the newer-generation pills available now would be safer regarding breast cancer risk. Yet a new study from Denmark found that even with the current pills, hormonal contraception users experienced a 20% increase in the risk of breast cancer compared to non-users; the odds rose among women who used hormones for more than 10 years. The risk was similar in magnitude to that of older pill types.

Whether oral contraceptive use increases the risk of liver cancer is not clear: while some studies found more cases of hepatocellular carcinoma ( a type of liver cancer) in women who took the pill for more than 5 years, others did not confirm this correlation.

Hormonal contraception seems to have a protective effect on colo-rectal (bowel) cancer, but this has not been yet consistently proven.

Since the pill seems to reduce the frequency of certain cancers and increase the risk of others, an interesting question arises: Does the pill increase the overall risk of cancer? The answer is NO. A recently published study provided epidemiological data on more than 40,000 women followed for more than 40 years. The results showed that users of oral contraceptives are protected from colo-rectal, endometrial, and ovarian cancer; this beneficial effect lasts for many years after stopping the pill. An increased breast and cervical cancer risk was seen in current and recent users, which appears to be lost within approximately 5 years of stopping oral contraception, with no evidence of either cancer recurring at increased risk in ever users with time. These results are reassuring and provide strong evidence that most women do not expose themselves to long-term cancer harm if they choose to use oral contraception; indeed, many are likely to be protected.

11) The pill has many bothersome side effects

TRUE AND FALSE. Some women refuse to take the pill because they fear certain annoying symptoms. Indeed, the birth control pill is a medication, and as such, it has possible side effects.

The most common adverse reactions associated with use of combined contraceptives include changes in bleeding patterns, nausea, breast tenderness, headaches, missed periods, vaginal discharge and visual changes with contact lenses; few women may also experience changes in sexual desire and mood changes, or temporary weight gain related to fluid retention (see above). In general, these side effects are not a sign of illness, and usually stop within the first few months of using the pill.

While some women may experience bothersome symptoms, the pill provides important non-contraceptive health benefits:

  • Decreased risk of certain cancers (see above)
  • Improved bone mineral density (in older women)
  • Protection against pelvic inflammatory disease
  • Prevention of ovarian cysts
  • Reduction of menstrual bleeding problems
  • Prevention of menstrual migraines (with non-stop formulations)
  • Protection against iron-deficiency anemia
  • Reduction of ovulation pain
  • Treatment of acne
  • Treatment of bleeding from fibroids
  • Treatment of dysmenorrhea (painful periods)
  • Treatment of excess hair on face or body
  • Treatment of premenstrual syndrome (PMS)
  • Reduction of endometriosis symptoms
  • Reduction of polycystic ovarian syndrome symptoms
  • Induction of amenorrhea for lifestyle considerations (when you need to stop your period for a while; you can also advance or delay your period with the pill)

So, how dangerous is the pill?

There is no perfect contraception method. I wish there were. And it is true that hormonal contraception, like any other medication, may have annoying side effects and serious health risks. Does it mean that no one should take the pill? Of course not!

We should keep in mind that severe risks are very rare and most bothersome symptoms are short-lived; in addition, the pill offers many non-contraceptive health benefits. But when discussing about the pill’s pros and cons, sometimes we forget a very important issue: the birth control pill is one of the most effective contraceptive methods. And effective birth control prevents from unwanted pregnancy, which may have not only devastating psychological consequences, but may also lead to severe physical harm.

Therefore, the potential problems of the birth control pill should be analyzed in perspective: we shouldn’t just pay attention to downsides, forgetting to place them in context with the upsides. Every woman considering taking the pill should thoroughly discuss with her healthcare provider not only the possible risks, but also its significant benefits, which for many women will be greater than the harms.

 

Photo credits

Heading: vintag.es; 1: thebump.com; 2: breakingmuscle.com; 3: thejewel.com; 4: health.harvard.edu; 5: newhealthadvisor.com; 6: pinterest.com; 7: pinterest.com; 8: pinterest.com; 9: blog.path.org; 10: purelyb.com; 11: buzzfeed.com; Conclusion: bigthink.com

HPV VACCINE: THE CONTROVERSY CONTINUES…

HPV Vaccine 2 adThis year is the HPV vaccine’s 10th anniversary, as the first cervical cancer vaccine was licensed by the US Food and Drug Administration (FDA) in June 2006. Should we celebrate or not? Arguably the HPV vaccine is one of the most controversial vaccines ever released…

In October 2015 I published the article: “The HPV vaccine controversy: science, media… and marketing”, where I included the information available on the vaccine, focusing on its safety and efficacy. A lot has happened since then, many articles have been published which, instead of clarifying the situation, have rather divided even more both the general public and the scientific community. The result: doctors hesitate to recommend the vaccine, parents and young women are even more confused when they have to decide whether to get vaccinated or not…

In this article I outline the recent events related to the HPV vaccine, focusing on new indications, safety statements and current controversies.

 

HPV-Associated Cancers are on rise

Malignancies related to HPV include cervical, vulvar, vaginal, penile, oropharyngeal, anal, and rectal cancers.

According to a new report from the USA Centers for Disease Control and Prevention (CDC), HPV-associated cancer incidence have increased from 10.8 per 100,000 persons during 2004–2008 to 11.7 per 100,000 persons during 2008–2012. The most common cancers are cervical and oropharyngeal (although not all oropharyngeal cancers are HPV-related).

The report stresses that a large number of these cancers are associated with the HPV types included in the vaccine, thus vaccination may potentially reduce the incidence of cancer in the future.

The same trend is observed in other countries such as the UK: while the incidence rates of cervical cancer for women aged 25-34 initially decreased by 35% between 1985-1987 and 2000-2002, rates have since increased by 50% in this age group.

 

More medical societies urge to increase HPV vaccination rates

HPV vaccine 2 ASCODespite many professional organisations recommending HPV vaccination, vaccine uptake in the United States remains low: about 39% of girls and 21% of boys have received the full schedule of HPV vaccines.

Taking into consideration these data, the American Society of Clinical Oncology (ASCO) has recently issued a statement urging to increase vaccination rates. In this article “ASCO stresses (…) the need to increase the proportion of adolescent boys and girls receiving the HPV vaccine (…) which could lead to complete eradication of HPV-related cancers in men and women”. They further emphasize its safety by stating that “Both Gardasil and Cervarix vaccines reported excellent short- and long-term safety results in clinical trials”.

But some issues in the ASCO statement have been questioned, namely the “complete eradication of HPV-related cancers” (as none of the available vaccines is 100% effective), and the “excellent safety results”, as worldwide reports of adolescents with chronic side effects after HPV vaccination continue to be published (see below). In addition, the report does not mention anything about screening tests (Pap smears), which are an indispensable tool for preventing cancer by early detection of precancerous lesions.

 

Changes in the HPV vaccination schedule

The CDC recently published the new 2016 recommended immunization schedule for children and adolescents. The schedule for HPV vaccination introduces the ninevalent (9vHPV) vaccine for males and females. While females may receive any of the three available vaccine types: 9vHPV (Gardasil 9), 4-valent (Gardasil) or 2-valent (Cervarix), only Gardasil 9 or Gardasil may be used for males.

The CDC also states that HPV vaccine should be administered beginning at age 9 years to children and youth with any history of sexual abuse or assault who have not initiated or completed the 3-dose series.

 

More studies confirming reduction in the prevalence of HPV, cervical abnormalities and genital warts 

Reduction of HPV prevalence

An American study confirms previous observations of HPV vaccine impact: within 6 years of vaccine introduction, there was a 64% decrease in the four HPV types included in the vaccine among females aged 14 to 19 years and a 34% decrease among those aged 20 to 24 years.

Decrease in condylomas in women and men

In Denmark, girls and young women have been vaccinated since 2008. A recent study shows a significant reduction in the incidence of genital warts, not only in women, but also in men, This means that the vaccine has caused what is called herd immunity. The study concludes: “The reduction is seen in both women up to 35 years of age and men aged 12 to 29 years, suggesting that HPV vaccination is highly efficient and that herd protection has developed.”

Reduction of abnormal Pap tests in high-risk patients

A new study demonstrated the HPV vaccine is effective in a real-world setting of high-risk patients (low-income females, engaging in high-risk sexual behaviors) many of whom had not completed the HPV vaccine schedule.

After following 4127 girls and young women from 11 through 20 years of age who underwent Pap smears, they found that abnormal cytology was less common in vaccinated vs unvaccinated females (8 vs 13 % respectively). The risk was lower if  the 3-dose vaccine series was completed or if the vaccine was administered from 11 through 14 years of age.

 

The European Medicines Agency concludes HPV vaccine is safe

In my previous article, I mentioned that the European Medicines Agency (EMA) would conduct a safety review of HPV vaccines, mainly due to the numerous reports on severe side effects, not only in lay media, but also in medical journals. The main concern was the occurrence of two particular syndromes, namely complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) (see here for more details), suspected to be related with HPV vaccination.

The long awaited EMA review was published in November 2015, and concluded that “the evidence does not support that HPV vaccines (Cervarix, Gardasil, Gardasil 9, Silgard) cause CRPS or POTS. The benefits of HPV vaccines continue to outweigh their risks”. Read their press release here.

After this review, a World Health Organization – Global Advisory Committee on Vaccine safety (GAVCS) Statement on Safety of HPV vaccines followed in December 2015, which declares ” The GACVS has systematically investigated safety concerns raised about HPV vaccines and has issued several reports in this regard. To date, it has not found any safety issue that would alter its recommendations for the use of the vaccine”. The statement refers specifically to CRPS and POTS, but also to the increased incidence of Guillain-Barre syndrome found in a French study (see my previous article).

 

Danish scientists skeptical about EMA’s conclusions, start independent research

It was Denmark that had requested the safety review of HPV vaccines from the EMA, as this country, with a high vaccine uptake, reported that more than 1300 girls and young women with chronic symptoms (POTS, CRPS) have been referred to specialized centers.

Not convinced with EMA’s conclusion, Denmark is conducting its own investigation into the issue. The Ministry of Heath has given 7 million DKK (US$1.01 million) for research leaded by specialists who are seeing girls with symptoms after HPV vaccination and who are independent of the pharmaceutical industry.

 

Nordic Cochrane Centre accuses EMA of maladministration and scientific misconduct

HPV vaccine 2 Cochrane NordicRecently, the reputed Nordic Cochrane Centre filed a complaint to the EMA expressing their concern about EMA’s handling of the HPV vaccine safety issue.

The Nordic group says that the EMA report is flawed, and points out several issues. Briefly:

  • The EMA has concluded that there is no causal link between CRPS / POTS and the HPV vaccine, but the Nordic Cochrane group says “The EMA’s official report gives the impression of a unanimous rejection of the suspected harms. However, the EMA’s internal report (…) tells a very different story. This “internal report is confidential but has been leaked,” the group notes, and it “reveals that several experts had the opinion that the vaccine might not be safe and called for further research, but there was nothing about this in the official report.”
  • “The EMA asked the pharmaceutical companies to search for side effects of the vaccine in their own databases and did not check the companies’ work for accuracy,” they say. They also allege that their criteria to consider cases as POTS were extremely restrictive: “In the search for cases coded as POTS (…)  almost half (40 cases) are dismissed for not meeting the case definition for POTS”.  “This is extraordinary, as the companies have a huge vested interest in not finding these possible harms in their databases,” the Nordic group comments.
  • Another issue is the placebo that was used in the clinical trials of HPV vaccines. “In all the vaccine trials apart from a small one, the control group was given a placebo that contained an aluminium adjuvant, which is suspected of being neurotoxic,” they note. The group quotes information contained in the leaked internal documents: “Initially, the vaccine was compared with a placebo group being vaccinated with physiological serum, whereby the number of adverse reactions was much higher and much more serious than in the control group. After comparing 320 patients in the saline placebo group, a quick move was made to an aluminium-containing placebo, in order to be able to only evaluate the effects of the active substance. However, this distorted the comparison (…)”. “We believe this constitutes scientific misconduct,” the Nordic group says.
  • The group highlights the “extreme levels of secrecy” that surround the EMA review process, in which experts who are involved in the process are not named and are bound by lifelong secrecy about what was discussed. Nordic Cochrane argues that instead, all documents involving HPV vaccination safety should be made publicly available.
  • They also question whether EMA has behaved fairly, in particular towards Dr. Louise Brinth, the Danish whistle-blower who first described cases of POTS in the medical literature, as EMA accuses her to report on “a sample of patients, apparently chosen to fit a pre-specified hypothesis of vaccine-induced injury”. The Nordic group concludes “We find that the EMA’s comments are unprofessional, misleading, inappropriate and pejorative, and that the EMA’s approach (…) is unscientific”.

Dr Brinth, who cosigns the Nordic Cochrane complaint, has published her own 63-page response to the EMA review (it’s really worth a read).

The situation in Japan

Japan puts in place a scheme to manage symptoms after HPV vaccination

HPV vaccine 2 japanese girls

Japan has put in place a scheme to manage symptoms, especially generalized chronic pain, that have arisen after HPV vaccination. Guidelines for the evaluation and management of symptoms that begin after HPV vaccine injection were issued to healthcare professionals and approved by the Japan Medical Association and the Japanese Association of Medical Sciences.

Class action lawsuit filed against Japanese government and vaccine manufacturers

Sixty-three women and girls who reported side effects from cervical cancer vaccines sued the Japanese government and drugmakers. “More plaintiffs are expected to join the suit “, The Japan Times recently reported.  According to the Japanese Ministry of Health, Labor and Welfare, 2,945 of the 3.39 million women who had received the vaccines, or 0.09 percent, have reported side effects.

Scientist accuses WHO, GAVCS, CDC of misconduct

In an open letter of complaint to the World Health Organization (WHO), Japanese Dr. Sin Hang Lee expresses concerns regarding the conduct of certain members of GACVS, WHO, CDC and other scientific/health professionals. “I have come into possession of documentation which leads me to believe multiple individuals and organizations deliberately set out to mislead Japanese authorities regarding the safety of the human papillomavirus (HPV) vaccines, Gardasil and Cervarix”, he writes.  In his letter he explains that there is at least one known mechanism of action explaining why serious adverse reactions occur more often in people injected with HPV vaccines than other vaccines, and why certain predisposed individuals may suffer a sudden unexplained death as a result, but he alleges that this information was deliberately “ignored” by the experts.

 

Potential risk of Primary Ovarian Failure associated with HPV vaccination

HPV vaccine 2 American-College-of-PediatriciansThe American College of Pediatricians (ACP) issued a statement in January 2016 warning of a potential relationship between Primary Ovarian Failure and HPV vaccination.

“It has recently come to the attention of the College that one of the recommended vaccines could possibly be associated with the very rare but serious condition of premature ovarian failure (POF), also known as premature menopause“, they report.

They further state that, although most physicians are probably unaware of a possible association between the HPV vaccine  and POF, and may not consider reporting cases or prolonged amenorrhea (missing menstrual periods) to the Vaccine Adverse Event Reporting System (VAERS), 213 cases were reported. When the cases are more carefully chosen:  “86/89 cases are associated with Gardasil, 3/89 with Cervarix, and 0/89 with other vaccines administered independently of an HPV vaccine. Using the same criteria, there are only 7 reports of amenorrhea from 1990 through 2005″.

“While there is no strong evidence of a causal relationship between HPV4 and ovarian dysfunction, this information should be public knowledge for physicians and patients considering these vaccines”, they conclude.

A possible association between ovarian problems and the HPV vaccine had been already reported by Dr Deirdre Little, an Australian gynecologist:

It should be mentioned that the ACP statement, as well as Dr. Little’s research have been heavily criticized by other physicians.

 

Conclusions

HPV vaccine 2 Should I get HPV Vaccine

I was hoping that, with the new available information on the HPV vaccine safety, I could reach a conclusion on how to counsel, as a physician, young women and mothers asking me whether to get the HPV vaccine or not. I was expecting to have a thorough review stating loud and clear the HPV vaccine expected benefits vs. the documented risks.  Unfortunately, no conclusion can be easily drawn so far. It is extremely difficult to find a balance between the scientific evidence -with studies not always well-designed-, the experts’ opinions and the increasing criticism surrounding this vaccine.

While most professional societies urge us to promote vaccination, the constant reports on serious side effects coming from all around the globe cannot be ignored. It’s unfortunate to see a woman dying of a cancer that could have been prevented, but it is equally heart-breaking to see a healthy teenager, full of life, suddenly prostrated in a wheelchair…

I have no doubt that vaccines are an invaluable public health tool against fatal diseases, and it’s imperative that we all continue to believe in vaccines. However, it’s my opinion that the HPV vaccine in particular deserves further study.

The unanswered questions are too many, not only about potential risks, but also about potential benefits. Therefore, I believe that further independent research is urgently warranted – not just in Denmark, but worldwide. With  more than 175 millions vaccine doses distributed in 63 countries, it is certain that a coordinated, global effort would shed light on some aspects of this controversial vaccine.

Acknowledgement

I am genuinely grateful to Ms Caron Ryalls, who kindly contacted me and provided me with some of the information presented here.

THE HPV VACCINE: WHY IS IT CONTROVERSIAL?

The HPV vaccine has been around for almost 10 years and more than 175 millions doses have been distributed in 63 countries, with several studies confirming its safety and efficacy. In spite of that, the vaccine still remains a subject of controversy. Although recommended by most scientific societies worldwide, some recent reports questioning its safety fuelled even more the debate, dividing both general public and medical community.

Embed from Getty Images

 

In this article we will analyse the existing evidence regarding the HPV vaccine, with particular focus on its efficacy and safety. In order to organise the available information, the article will be divided into the following sections:

  1. Getting to know HPV
  2. Why a vaccine? The burden of HPV-related diseases
  3. The three available HPV vaccines
  4. Vaccination schedule and timing 
  5. Efficacy of the HPV vaccine
  6. Safety of the HPV vaccine
  7. Recent safety concerns: the chronicle of events
  8. Other debatable issues
  9. Unanswered questions…
  10. Conclusion

1. Getting to know HPV

HPV vaccine cure cancer awarenessHPV (human papillomavirus) is a virus and is transmitted from person to person through skin-to-skin contact.

  • HPV infection is extremely common, and most of the times it will be cleared by the immune system.
  • Of the over 100 types of HPV, about 12 subtypes of the HPV (mostly subtypes 6 and 11) may cause genital warts (also known as condylomas). These so-called “low-risk types” can also cause a rare condition called recurrent respiratory papillomatosis, in which warts grow in the throat.
  • Approximately 15 types of HPV (most commonly types 16 and 18) are related to cancer. While cervical cancer is the most common HPV-related cancer, this virus can also cause other cancers: vulvar, vaginal, anal and oropharyngeal (mouth and throat),  as well as penile cancer in men.

You can read more detailed information on HPV here.

 

2. Why a vaccine? The burden of HPV-related diseases

HPV vaccine every 2 minutes a woman diesThese figures will give you and idea of the magnitude of the problems caused by HPV:

-Worldwide, over 500,000 new cervical cancer cases are diagnosed annually. Cervical cancer ranks as the 4th cause of female cancer in the world and is the 2nd most common female cancer in women aged 15 to 44 years (1).

In the United States, an estimated 26,000 new cancers are attributable to HPV each year, about 17,000 in women and 9,000 in men (2) .

In Europe, about 58,000 new cases of HPV-related cancers are estimated to occur every year (3).

-Regarding  precancerous lesions, the estimated annual burden of high-grade precancerous lesions ranges between 280,000 and 550,000 new cases per year in Europe (4).

-In addition to cancers and precancerous lesions, the problem of genital warts should also be taken into consideration. Genital warts are very common: 1 out of 10 persons will have condylomas at some point in their lives (the frequency varies according to different countries between 0,3 and 12 %) (5). About 800,000 new annual genital warts cases are estimated to occur in women and men in Europe (4). Although not life-threatening, the costs derived from their treatment and their psychological burden should not be neglected.

 

3. The three available HPV vaccines

HPV vaccine collageFrom 2006, 2 vaccines have been available: One bivalent (Cervarix®), directed against HPV types 16 and 18, responsible for about 70% of cervical cancers  and other HPV-associated cancers; the other quadrivalent (Gardasil® of Silgard® in different countries) containing 4 HPV types:16 and 18, together with HPV 6 and 11 which are responsible for more than 90% of genital warts.

In December 2014, the American Food and Drug Administration (FDA) approved a nine-valent vaccine, Gardasil 9® (6), which, besides the 4 strains contained in Gardasil (i.e., 6,11,16,18), includes types 31, 33, 45, 52, and 58, responsible for an additional 20% of HPV-related cancers (4). Gardasil 9 has also been recently approved for commercialisation in Europe (7).

 

4. Vaccination schedule and timing 

HPV vaccine who should get it ACIPinfographic

  • Vaccines are given as a 3-dose series, Gardasil at 0, 2 and 6 months, Cervarix at 0, 1 and 6 months (8).
  • In the States, The Advisory Committee on Immunization Practices (ACIP) and  the American College of Obstetrician and Gynecologists (ACOG) recommend that girls be routinely vaccinated at age 11 or 12 years.
  • Since 2010 boys have been included in the vaccination schedule in the USA, with the same schedule as girls.
  • If not vaccinated when they were younger, girls/young women and boys/young men should be vaccinated through age 26 (9).
  • Vaccine may be given starting at age 9 years (9, 10).
  • A reduced, 2-dose schedule is recommended by the World Health Organization (WHO) for those aged 9-13 years; this schedule is not recommended by the ACIP but it has been adopted by many countries.HPV vaccine Protect your children
  • Earlier vaccination (before age 14) results in higher immune response. Another argument in favor of early vaccination is the fact that vaccines are more effective before the onset of sexual activity (8).
  • Vaccination is recommended regardless of sexual activity or known HPV infection. Although vaccines seem to be less effective in sexually active people, some benefit is expected to be attained since exposure to all types of HPV included in the vaccines is very unlikely. Testing for HPV is NOT recommended before vaccination.
  • The vaccines are prophylactic, that is, they do not prevent progression of existing infection to disease or treat existing disease. (2)
  • The HPV vaccine is covered by most private health insurance and government insurance programs worldwide. Vaccinations schedules may vary in different countries.
  • There seems to be additional protection by the vaccine in women through age 45, as showed by certain studies (11). However, there is no recommendation for vaccination in individuals aged 26 to 45.
  • The same schedule applies for Gardasil 9 (0, 2 and 6 months). Revaccination with the nine-valent vaccine is not recommended in persons who previously completed the three-dose series with the bivalent or or quadrivalent HPV vaccine (8).

5. Efficacy of the HPV vaccine

HPV Vaccine Charlene-Choi1The ultimate goal of the HPV vaccine is to reduce the incidence of HPV-related cancers. For obvious ethical reasons, the endpoint set to evaluate the HPV vaccine efficacy in different studies was precancerous lesions, namely CIN 2 and 3 (high risk lesions of the cervix, with potential to evolve to cancer). Other efficacy endpoints evaluated were incidence of HPV infection and incidence of condylomas.

Studies conducted before licensure showed that both vaccines achieved a high level of protection: 98-100% for the HPV types included in the vaccine in a naive population (that is, women who did not have HPV 16 or 18 at the time of  vaccination),  although the protection against precancerous lesions was 30-40% in the total vaccinated cohort (which included women who did not finish their immunization plan, or that were already infected with the virus before vaccination) (12, 13, 14, 15). There was also cross-protection for other types of HPV (i.e., HPV 45 and 31), which was more intense with Cervarix (16).

HPV vaccine AustraliaThe impact of vaccination on the general population has also been analysed in some studies. Australia was the first country to introduce an organised HPV vaccination program, achieving one of the world’s highest vaccination compliance rates.  Since 2007, when the National HPV vaccination program started with the quadrivalent vaccine, HPV infections from the types included in the vaccine decreased from 29% to 7% (17); a 93% reduction in the diagnosis of genital warts was also observed (18). Moreover, other recent studies showed an almost 50% reduction of  high-grade cervical precancerous lesions in women who had received all required doses of the vaccine (19).

Denmark also counts with an organised vaccination program. Six years after licensure of the quadrivalent HPV vaccine, a reduction of cervical precancerous lesions was observed, which was 80% in younger patients (20).

Recently, a study was conducted to evaluate the efficacy of the nine-valent vaccine. Gardasil 9 prevented 97% of high-grade precancerous lesions of the cervix, vulva, and vagina caused by the five new high-risk HPV types (HPV31/33/45/52/58) (21). The nine-valent vaccine also generated immune responses to HPV6/11/16/18 that were as good as or better than those generated by the quadrivalent vaccine. (4, 22)

 

6. Safety of the HPV vaccine

Many studies have evaluated HPV vaccine safety, both before their commercialisation and post-release, which demonstrated no differences in side effects as compared to control groups, irrespective of age and ethnicity (23).

HPV vaccine armed against cancerAccording to the CDC, the most commonly reported side effects of the vaccines are:

  • Pain, redness, or swelling in the arm where the shot was given
  • Fever
  • Headache or feeling tired
  • Nausea
  • Muscle or joint pain

Fainting (also known as syncope) and related symptoms (such as jerking movements) is not uncommon (24), especially in teenagers. For that reason, it is recommended that people receiving the HPV vaccine sit or lie down during vaccination, and remain seated for 15 minutes after the shot. (23)

Considering the target age of vaccination (which includes women in reproductive age), pregnancy outcomes received special attention. No increase in miscarriage rates has been reported for either of the vaccines (25). In addition, pregnant women that were recorded and observed in registrative trials did not have increased rate of congenital abnormalities (26, 27, 24).

Studies have also demonstrated efficacy and safety of the vaccines in men, both in heterosexual and men who have sex with men (28).

Serious side effects are very rare (less than 0.5%) (29), the most common being persistent headache, hypertension, gastroenteritis, bronchospasm and anaphylaxis. Their reported incidence is similar to that of other compulsory vaccines types (30).

HPV vaccine third pokeCertain side effects have been a matter of concern since the introduction of the vaccine, namely autoimmune diseases (AD) (i.e., hypothyroidism, rheumatoid arthritis, Behçet’s syndrome, Raynaud’s disease, type 1 diabetes, and vitiligo), neurological disorders (such as epilepsy, paralysis, Guillain–Barré syndrome, central demyelination, and multiple sclerosis) and venous thromboembolism (a blood clot that plugs a vein). It should be mentioned that ADs are not rare in adolescents and young adults, particularly in women. Therefore, it is a real challenge to distinguish causal from temporal association. A recent study gathered the results of 9 large studies (of which one was an analysis of 42 trials together, or metanalysis) in order to investigate severe adverse reactions after the HPV vaccine. None of the included studies found evidence of increased risk of autoimmune disease, neurological disorder, or venous thromboembolism (31).

The Global Advisory Committee on Vaccine Safety (GACVS), established by the World Health Organization (WHO) provides independent, scientifically rigorous advice on vaccine-safety issues. In December 2013, the committee reviewed different topics and considered all available evidence on the safety of HPV vaccines, and concluded that both commercially available vaccines are safe (32). Likewise, the International Federation of Gynecology and Obstetrics (FIGO) Gynecologic Oncologic Committee and Subcommittee for Cervical Cancer Prevention support the continued administration of the HPV vaccines in appropriate populations (33).

7. Recent safety concerns: the chronicle of events 

HPV vaccine Japanese_SchoolgirlsAlthough some isolated cases of side effects had been described in UK and Australia (34), Japan was the first country reporting on several girls suffering from severe pain and disability; these cases were heavily publicised in newspapers, TV news and social media, but they also alarmed the medical community. Japanese physicians published later on a series of 44 girls who were diagnosed with complex regional pain syndrome (CRPS) (35). Due to these concerns, in June 2013 the Japanese Ministry of Health, Labour, and Welfare (MHLW) decided to suspend its active recommendation of HPV vaccination. This decision created intense debate among scientists and general public, which continues until nowadays (34).

In March 2015, Denmark‘s TV channel TV2 aired a documentary entitled The Vaccinated Girls – Sick and Betrayed. The journalists gathered about 60 girls from all over Denmark who became sick shortly after receiving the HPV vaccine. Among the doctors interviewed is Louise Brinth, who examined approximately 80 girls with similar symptoms potentially caused by the HPV vaccine. Dr. Brinth noted that the girls experience symptoms such as dizziness, passing out, and severe headaches. She said, “They have abdominal pain and nausea. They have weird muscle movements they cannot control. And they’re very tired… We see a pattern that screams to heaven, and that should be examined by some solid research.”

HPV vaccine Danish documentaryIn April 2015, Dr. Brinth reported in a scientific journal on 53 patients complaining of orthostatic intolerance, severe headache, excessive fatigue, cognitive dysfunction, gastrointestinal discomfort and widespread pain. Most of them were diagnosed with a rare syndrome known as postural orthostatic tachycardia syndrome (POTS), and all of them were in close temporal association with the HPV vaccine (36a, 36b).

Denmark’s documentary has had a huge impact worldwide, both in the general public and the medical community. A closed Facebook page set up for suspected victims of adverse reactions to Gardasil in Denmark tripled its -careful verified- members; similar Facebook groups were created in other countries.

At the request of Denmark, The European Medicines Agency (EMA) is currently conducting a safety review of HPV vaccines. However, the agency emphasizes that this review “does not question that the benefits of HPV vaccines outweigh their risks.”The agency also notes that while the review is being carried out, no change in the use of these products is recommended. See the EMA’s review conclusions here.

HPV vaccine reactions independent UKIn May 2015, UK’s newspaper The Independent published an article entitled: Thousands of teenage girls report feeling seriously ill after routine school cancer vaccination. The article focuses on the story of Emily Ryalls, 17, who started feeling intense pains and difficulty breathing soon after receiving the HPV vaccine.

Mrs Ryalls reported Emily’s symptoms to the Medicines and Healthcare Products Regulatory Agency (MHRA), and she was not alone: adverse reactions after HPV vaccination numbered 8,228, of which 2,587 were classified as “serious”; that’s substantially more that those reported with other compulsory vaccines (see graph). The MHRA, though, said it had no concerns on the numbers of adverse reactions related to the HPV vaccine and that the “expected benefits in preventing illness and death from HPV infection outweigh the known risks”.

Emily’s mother, together with other 80 families in similar situation across the UK have formed the Association for HPV Vaccine Injured Daughters (AHVID).

As stated by the newspaper “This article created significant debate among medical professionals, journalists and members of the public…”.

HPV vaccine France fiasco SV-1136-vaccin-HPVIn France, the National Security Agency of Medicines and Health Products (ANSM) just published (September 2015) the results of the follow-up of more than 2 million girls aged 13-16 years, vaccinated between 2008 and 2013 to evaluate the occurrence of side effects, mainly autoimmune diseases. When analysed all the diseases together, their results showed no overall increased risk of occurrence of serious events. However, when each disease was analysed individually, a four-fold increase in the occurrence of Guillain Barre syndrome was observed. The study also found an increased risk of Inflammatory Bowel disease, but the association was weak.

The authors conclude: “…the results of the study… prove reassuring regarding the risk of autoimmune disease associated with the HPV vaccines. The expected benefits of this vaccination in terms of public health are far greater than the eventual risks the girls may be exposed to” (37). In spite of these “reassuring” results, the vaccination rate in France continue to be low (less than 30%).

HPV vaccine POTSIn September 2015, another report provided details on 45 individuals from 13 countries who developed a chronic ailment soon after receiving the HPV vaccine. “A disabling syndrome of chronic neuropathic pain, vexing fatigue, and profound autonomic dysfunction may appear after HPV vaccination,” say the authors, headed by Manuel Martínez-Lavín, MD, a specialist in chronic pain conditions from Mexico City. After a mean period of 4 years following HPV vaccination, 93% of individuals “continue to have incapacitating symptoms and remain unable to attend school or work,” write the authors (38).

POTS after HPV vaccination has also been reported in the United States.  Dr. Blitshteyn, a neurologist from New York, described six patients who developed POTS between 6 days and 2 months after HPV vaccination. All patients reported improvement over 3 years, but residual symptoms persisted (39).

The US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) emphasised that controlled clinical trials in tens of thousands of individuals plus postlicensure monitoring of millions of individuals have found no causal association between HPV vaccination and atypical pain syndromes or autonomic dysfunction.

HPV vaccine Diane HarperDr. Diane Harper, an american obstetrician & gynecologist, is one of the HPV experts called in to design the clinical trials of Gardasil and Cervarix.  Although initially in favour of the vaccine, in recent years she has questioned Gardasil safety. She stated that “Gardasil has been associated with at least as many serious adverse events as there are deaths from cervical cancer developing each year”. Moreover, in an article published in December 2009 she concluded that, given the various limitations and risks of the vaccines, the benefits and risks of HPV vaccination must be weighed with the benefits and risks of HPV screening (Pap smears) to reduce cervical cancer in a cost-effective manner (40).

Dr. Harper does not support mandatory HPV vaccination for schoolchildren, because she believes that the duration of protection may be too short (see below). She has also criticised the short period of time vaccines were tried before its licensure,  and the misleading publicity carried out by the pharmaceutical companies. Learn more here.

8. Other debatable issues

Vaccination in boys

HPV vaccine is cancer prevention.

The rationale of vaccinating boys is to reduce the transmission of the HPV virus to women and to protect them against oral and anal cancers (41). Since these cancers are very rare, it has been questioned by some scientists whether is it worth to expose millions of boys to potential vaccine side effects in order to protect girls, or to prevent a so rare type of cancer (responsible for just 300 deaths in the USA); whether the benefit outweighs the risk and if men vaccination is cost effective. While countries such as Australia and the USA include boys in their vaccine recommendations, other countries (i.e., UK and France) have not yet adopted this measure.

Men who have sex with men are a special category, since they are at higher risk of anal cancer. Thus, some experts believe these men (and not every boy) should be offered the vaccine. However, this measure may be difficult to implement: in order get covered by their insurance or social security, young men may be required to declare their sexual preferences.

Immunogenicity of Gardasil vs. Cervarix

HPV vaccine ArgentinaImmunogenicity means the ability of the vaccine to provoke an immune response; in other words, the “strength” of the vaccine.

Most countries adopted vaccination with Gardasil instead of Cervarix assuming equal protection for cancer, with the “bonus” protection against genital warts. But is it really like this?

Several studies have demonstrated that Cervarix elicits stronger and longer-lasting immune response than Gardasil (42, 43).

These laboratory findings have also been confirmed by some clinical studies: Over the years, the efficacy of the Cervarix to protect vaccinated women from precancerous lesions (total vaccinated cohort-naive) was 93%, while Gardasil’s dropped to 43% (44)

Age of vaccination

HPV vaccine school girlThis subject has also raised intense debate and concern. As stated above, immune response provoked by the vaccines may be of limited duration, especially for Gardasil. This can be a serious limitation of the vaccine because, as Dr. Harper noted “… if the HPV vaccine does not last for at least 15 years, no cancers will ever be prevented; women will just get the cancers at a later time in life after the vaccine has worn off“.

If this short protection span is confirmed by clinical studies, a boost dose would solve this limitation. However, this would increase considerably the cost of the vaccine; moreover, women who don’t comply with this recommendation will become unprotected over time.

Increase of promiscuity?

Many people feared that the the HPV vaccine would lead girls to promiscuous behavior. This was actually investigated by some studies, and have proved not to be true: no increase in sexually transmitted diseases was observed among vaccinated girls (45), showing that vaccination is unlikely to promote unsafe sexual activity.

9. Unanswered questions…

  • HPV cancer vaccine flyer - 8-1/2 x 11Will the HPV vaccine reduce cervical cancer deaths in real-world conditions?
  • In light of the latest publications, should vaccination programs be halted until the situations is clarified?
  • Due to these latest concerns, will more women opt for no vaccination, missing the opportunity to be protected against cancer?
  • Since the syndromes potentially related to vaccines are difficult to diagnose, is it possible that they have been underreported in the past? Could they possibly become over reported in the future?
  • Will the vaccine create a false sense of full protection against cervical cancer, resulting in less women attending screening programs?
  • Will the vaccine lead to a reduction of the HPV types included in the vaccine, but to an increase of those not included in the vaccine?

10. Conclusion

HPV vaccine End-cervical-cancer-posterIt is indeed exciting to have a vaccine that protects against cancer. After seeing women dying from cervical cancer, I truly wish that cervical cancer will be eradicated in the future. But we MUST be sure that we don’t create more harm than good in the process.

HPV vaccine smear for a smear campaignI am in favor of vaccines. Vaccines have done a lot of good to humanity (just imagine if we would still have small pox, or poliomyelitis…). It is true that every single medical practice may come with side effects, and this include vaccines. But we MUST know exactly what are the vaccine risks, and whether the benefits outweigh the risks.

I firmly believe that governments, scientific societies and pharmaceutical companies MUST do an effort to inform people in a responsible and honest manner, so that all of us -young people, parents and physicians- continue to believe in good science, and vaccines don’t lose their credibility.

It will take 10 to 20 years to figure out the true benefit of the HPV vaccine. In the meantime, keep in mind that Pap tests never killed anyone, on the contrary, they have saved millions of lives. Therefore, don’t forget your Pap smear!

 

Read on the latest events related to the HPV vaccine here.

 

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  1. International Agency for Research on Cancer, World Health Organization. Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012
  2. CDC Grand Rounds: Reducing the Burden of HPV-Associated Cancer and Disease. Morbidity and Mortality Weekly Report (MMWR) January 31, 2014 / 63(04);69-72
  3. Human Papillomavirus and Related Diseases Report. hpvcentre.net March 20th, 2015
  4. Hartwig S, et al: Estimation of the epidemiological burden of HPV-related anogenital cancers, precancerous lesions, and genital warts in women and men in Europe: Potential additional benefit of a nine-valent second generation HPV vaccine compared to first generation HPV vaccines. Papillomavirus Research, In Press (Available online 16 June 2015)
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  37. Vaccination contre les infections à HPV et risque de maladies auto-immunes : une étude Cnamts/ANSM rassurante – Point d’information 13/09/2015
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Photo Credits

Intro: Getty images; 1: curecancer.org; 2: m2.behance.net; 3: (collage) wikimedia commons; 4: cityofchicago.org; nkytribune.com; 5: english.cri.cnhpv.health.gov.au; 6: marketingmag.cascontent.cdninstagram.com; 7: Japan: wikimedia commons; Denmark: vaccineimpact.com; UK: independent.co.uk; France: science-et-vie.com; POTS: pinterest.com; Harper: initiativecitoyenne.be; 8: bphc.orgmigueljara.files.wordpress.comlh3.googleusercontent.com; 9: healthvermont.gov; 10: compasscayman.comi.dailymail.co.uk

HPV: ALL YOU NEED TO KNOW

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You got your Pap test result: “HPV”. What do you do? What most of us do: you google it! You go from one site to the other, from forum to forum … and you get really confused: I have what?!? How did I catch it? Will I have cancer? Is my partner cheating on me? A lot is being said and written about HPV, a great part of it being contradictory! The truth is, many things about HPV are still a mystery, even for physicians… Let’s try to get things straighten out and answer the most common questions regarding HPV….

  • Getting to know HPV

HPV stands for human papillomavirus. It’s a virus and is transmitted from person to person through skin-to-skin contact. HPV is in fact a very large family, comprising more than 120 subtypes; of those, only 30 infect the genital area.

  • How common is HPV infection?

Very common! It is estimated that 80% of women will contract the virus at some point in their lives. Most of the times, the immune system will be able to get rid of the virus, but a small percentage will keep it for life. It seems that many women will catch it and fight it several times in their lifetimes…

  • How did I get HPV? Who gave it to me?

The primary source of transmission is sexual contact, including vaginal, oral or anal. Actually, sexual intercourse is not required to get infected, as HPV can be spread by skin-to-skin contact. Although some research suggests that HPV could be transmitted through items such as towels or underwear, this is not yet clear. On this subject, the opinions are divided between experts, and many (including myself) feel that it is extremely unlikely, if not impossible, to catch the virus this way. Α pregnant woman, in rare instances, may transmit HPV to her baby, but the transmission route (vaginal the moment of delivery, or through the placenta during pregnancy) is not yet clear.

  • Is there any way of knowing how long I’ve had HPV?

Once you get infected with HPV, it may either show itself (usually 1 to 3 months after), or lay dormant and undetectable. Then the virus may be later cleared completely by the immune system, or remain present in the cervical cells for years. Because it can last long in your body before any cell changes occur, it is difficult to know who transmitted HPV to you or how long you’ve had it. So the answer to this question is: NO.

  • I got HPV! What will happen to me now?

-Most of the times, absolutely nothing. The majority of HPV infections will be cleared by your immune system without you even noticing it.

-Of the over 100 types of HPV, about 12 subtypes (mostly subtypes 6 and 11) may cause genital warts (also known as condylomas). These are growths that may appear on the external genitalia, but also around the anus, inside the vagina or on the uterine cervix. Genital warts are very common: 1 out of 10 persons will have condylomas at some point in their lives (the frequency varies according to different countries between 0,3 and 12 %). It is important to remember that genital warts are benign and do NOT evolve to cancer.

-Approximately 15 types of HPV (most commonly types 16 and 18) are related to cancer. All these types are known as “high risk types”. While cervical cancer is the most common cancer related to HPV, and HPV seems to be almost the exclusive cause of cervical cancer, this virus can also cause other, less frequent cancers: vulvar, vaginal, anal and oropharyngeal (means throat and tongue). Because a lot has been said lately about the possibility of getting cancer of the throat with oral sex, it is important to clarify that: Yes, HPV is related to throat cancer, BUT this is a not a very common cancer and only half of all throat cancers are caused by HPV!

-Low-risk types can also cause a rare condition called recurrent respiratory papillomatosis, in which warts grow in the throat.

  • What about men?

Things are less clear for men, as HPV is more difficult to test than in women. It is accepted that men are carriers of the virus and contribute to its widespread presence, so it can be assumed that HPV infection is as frequent in men as in women. What is sure is that men are much more rarely affected by the virus, with the exception of genital warts (same as women). Although rare, men may develop HPV-related anal or oropharyngeal cancer. HPV may be also related to penile cancer, but this type of cancer is extremely unusual.

  • I got infected with a high risk-type HPV. Will I have cancer?

When we get infected with a high risk-type virus, it may enter the cells and damage their DNA, causing then to grow abnormally. These cellular changes may progress to what is called dysplasia or cervical intraepithelial neoplasia (CIN). Most of the times, the immune system will destroy the abnormal cells before they become cancer. But sometimes they are not cleared by our body’s defense, allowing them to evolve, first to a mild lesion, then to a moderate, then to a severe lesion, which in turn, after several years may result in cancer. The transformation of these cells into cancer has to do with a balance between the aggressiveness of the virus and how strong our immune system is: the stronger will prevail…

  • Can we stop the virus before going into cancer?

Yes! Thanks to a Greek scientist, Dr. Georges Papanicolaou, we learnt that cervical cancer can be found before becoming cancer, that is, at its precancerous state. The Pap test (named after him) can detect early signs of abnormal cell changes of the cervix, allowing early treatment so they do not become cancer. There are other, more sophisticated tests, such as HPV testing and colposcopy that can be used as complementary exams t to the Pap test.

  • How can I avoid HPV infection?

That’s a difficult question. A sexually active person will never be 100% protected against HPV. We can though take some measures to reduce the chances of infection:

-Limit the number of sexual partners: although you may get HPV even if you had only one sexual partner in your lifetime, the more partners you have, the more the changes of getting infected.

-Use condoms. Condoms offer only partial protection against HPV infection as the virus can also be passed by touching infected areas not covered by a condom. The protection of condoms is estimated to be around 60%, that’s something, though ! and in fact is the only mean we have to be protected. Condoms should be used for vaginal, anal or even oral sex.

-Get vaccinated. Two vaccines are available to protect against certain types of HPV. This topic deserves further analysis in a future post…

  • What can I do to fight HPV?

There is no treatment for HPV itself, only for the problems that the virus can cause. These are some measures you can take to help your body get rid of the virus or at least prevent it from evolving into more severe lesions:

-Boost your immune system. The virus takes profit of a low defense system to progress. To help your immune system eat healthy, sleep well, avoid stress (if that is possible…), exercise, do activities that make you feel relaxed…Read more here.

-Quit smoking. Some chemical contained in cigarette will help the virus to progress into cancer.

-Get off the pill. Although the pill protects against uterine and ovarian cancer, it doubles the risk of cervical cancer…

In conclusion, if you got HPV:

First of all: don’t panic!

Second: get always good quality information on the subject. Don’t rely on rumors or on “what someone told you”. Knowledge is power!

Last, but not least, visit regularly your gynecologist. It takes 5 minutes to have a Pap test done. These 5 minutes can save your life!

References

http://www.cdc.gov/std/hpv/stdfact-hpv.htm

http://www.acog.org/~/media/For%20Patients/faq073.pdf?dmc=1&ts=20140707T0129049372

http://www.biomedcentral.com/1471-2334/13/39