We’ve all been hearing more and more about HPV infections; that they cause cervical cancer, vaginal cancer, anal cancer, throat cancer, mouth cancer and venereal warts. I’ve written several articles about the need to immunize girls and boys with the HPV vaccine. The most common vaccine, Gardasil is given in 3 doses, it is a quadravalent vaccine, which means it gives immunity to 4 types of HPV (6,11,16 and 18). These are the ones that cause 70% of cervical cancers, many of the other above mentioned cancers as well as venereal warts. But alas, despite the multiple direct to consumer ads in the media, recommendations by most doctors and the studies in peer-reviewed journals, only one third of adolescents are currently being immunized.

We would certainly expect the prevalence of these infections to be significantly diminished in those whose parents had the clinical acumen to have their children immunized. But they represent just 30% of their peers. So it was pleasantly surprising to find that a study published online in the Journal of Infectious Diseases reported that the prevalence of infections with the human papilloma virus types included in the Gardasil vaccine dropped by almost 60% among females aged 14 to 19 years during the four-year period after the vaccine became available and was recommended. Dr. Thomas Frieden, the CDC director, said during a press conference held to announce the results of the study, that increasing the vaccination rate to 80% would prevent about 50,000 cases of cervical cancer among girls alive today. “We owe it to the next generation- our sisters, our daughters, our nieces and to protect them against cervical cancer.”

Just to remind you, a three dose series of the quarivalent HPV vaccine was recommended in 2006 by the CDC as a routine vaccination for females age 11 to 12 years and for females aged 13 to 26 years who had not been previously vaccinated. In 2011, the recommendation for the vaccine was expanded to include boys aged 11 and 12 years and for non vaccinated males up to 26 years. No data is yet available on the proportion of males who have been vaccinated and/or the impact of vaccination on their infection rates.

The nearly 60% drop in HPV infection is greater than expected but can be due to “herd immunity” from vaccination (nothing to do with animals, it means that those who got the vaccination were unable to infect those who did not).

Remember, HPV is the most common STD in United States. The estimate is that 14 million people becoming infected with HPV every year. According to the CDC, 79 million of the those who have become infected with HPV are in their late teens and early 20s. Every year, about 19,000 cancers in women are caused by HPV; most are cervical cancer. And of 8,000 cancers caused by HPV that occur in men in the United States, most of them are oropharyngeal (mouth and throat).

Wow, this vaccine can make a huge difference. It may be too late for many of us who are over the age of 26 but we certainly can make sure that the younger (and youngest) generation are vaccinated… Not to do so is malparenting!

I’m currently at 39,000 feet on my way to NY to have a fun weekend with my daughter. I slipped a few medical journals into my carry-on to review so that I could find an article to share in my weekly newsletter. The seat is cramped, the cabin is crowded, most of my fellow passengers are sleeping….I passed over articles on multiple therapies for tuberculosis (too much coughing going on around me), sepsis and organ failure, as well as AIDs – defining cancers (too depressing)…Each subject is critical to the progress of medicine and I did read up on them, but for this newsletter I selected an article in JAMA titled ” Genital Shedding of Herpes Simplex Among Symptomatic and Asymptomatic Persons with HSV-2 Infection”.
So here it is…answering the question: do individuals who don’t know they have genital herpes shed the virus (and hence can spread it to a partner) to the same extent as those that have recurrent lesions (and are aware of their diagnosis)?

A quick herpes review: Genital herpes (HSV-2) is unfortunately, extremely prevalent. Over half a billion people worldwide have the virus and it is estimated that 23.6 million persons aged 15 to 49 become infected annually. In the US, 16% of adults have had it as evidenced by the fact that they have antibodies to HSV-2, but only 10 to 25 % of persons with this “everlasting infection” know that they harbor it. As a result, individuals who don’t know they have had herpes spread most of the HSV-2 infections. The risk of sexual transmission doesn’t correlate with recognition of symptoms but is correlated with silent viral mucosal shedding (and obviously, sexual contact with a partner).

Researchers at the University of Washington enrolled participants who were 18 and older in this herpes study for the published study. They advertised for participants through word of mouth at the university, newspaper ads (and promises of payment), tested many and in the end found 498 individuals who had antibodies to herpes 2. They then divided them into 2 groups: those who were symptomatic (had a clinical history of genital herpes) and those who were not (never knew that they had a lesion, their diagnosis was made with the herpes antibody blood test). Each person then self-collected swabs of their genital secretions for at least 30 days. (The swabs were examined by quantitative polymerase chain reaction for HSV DNA…I had to add that for the purists.)

The results showed that those who had symptomatic genital lesions were twice as likely to shed the virus and 3 times more likely to develop lesions than those who were, on initial testing, asymptomatic. However in those with no symptoms, genital HSV shedding did occur on 10% of days, and almost all of it was subclinical (i.e. the person did not recognize a lesion). There was a similar shedding rate between men and women; which means that men can have sub-clinical shedding on normal appearing genital skin. (There goes the adage, look before you engage…)
What they also found was that many of those who were initially asymptomatic begin to recognize recurrent herpes once they had received the diagnosis through their blood tests. They may have felt that what they had in the past was just a mild irritation or itch and ignored it, now they didn’t.

I have frequently been the doctor who sees a patient with “something down there” and either through direct culture and/or a blood test have made the diagnosis of herpes. Often the first statement posed by my now horrified patient is “he never told me”, or “was he with someone else?” Neither may be correct…the partner may not have known that he (or she) had acquired herpes in the past, or the woman with the “new” herpes infection may have had it all along and only now has become aware of a clinical lesion. (Perhaps brought on by illness, stress or diminished immunity.)

It certainly would be helpful to have universal herpes 2- antibody testing. But this is not currently a part of “routine” blood tests, nor is it financially feasible. The best protection will continue to be the use of condoms. For those who have been diagnosed with herpes, daily prophylactic use of the antiviral medications such as Valtrex or acyclovir should decrease shedding as well as recurrent lesions. So far that’s the best advice that’s offered by the experts. Somewhat depressing at 39,000 feet (or for that matter at sea level)!

As most of you know there are 2 kinds of herpes infections:

Herpes 1 (HSV-1), which when activated causes sores on the lips, gums and even the eyes. (It used to be called the herpes above the waist.)
Herpes 2 (HSV-2) or genital herpes, which can appear on the labia, vagina cervix (obviously in men in different genital areas…) and all sorts of places on the lower body (inner thighs, buttocks, back)….this is the one we are most concerned about.
A recent postgraduate Obstetrics and Gynecology publication gives an excellent synopsis on herpes and I thought it would be appropriate to go over some of the facts that were presented in this review.

HSV is a DNA virus and is classified as either 1 or 2 by its glycoproteins (i.e. not by where it infects but what is in its molecular structure). It’s transmitted though direct contact with mucosa or abraded skin. That’s the official wording…. when it comes to HSV-1 in “lay” expression you get it from kissing, or oral contact including oral sex. When it comes to HSV-2, transmission is through genital contact…. pretty easy to imagine how it can occur with intercourse, but those lesions women often get on their buttocks, back or thigh can occur via post coital contact (spooning, or getting close to a member that is shedding the virus…. member here usually refers to a penis).

Once transmitted, the virus incubates for 2 to 12 days and then replicates in the layers of the skin causing inflammation and ulceration. But that’s not all…. the virus then enters the sensory neurons and then travels to their root (or ganglia) where it then becomes dormant.  Weeks, months or years later it can become reactivated, spread back down along the nerve root to the skin and cause a recurrent ulcer-like lesion or simply shed from the skin without a visible sore or irritation. Antibodies to the virus develop within several weeks of the infection. The initial infections tend to be more severe than recurrent ones; there may be swelling of adjacent lymph nodes and the lesions may last 3 to 6 weeks. Recurrent infections are usually mild and last 3 to 10 days.  The frequency of recurrences can vary…. they are more likely to occur when your resistance is diminished, i.e. you are sick, have a fever, or are physically or emotionally stressed. After the first infection, about 50% of individuals will have a recurrence in 6 months.

The estimate of how many of us have had HSV-1 or HSV-2 is based on antibody testing which if positive is termed seroprevalence. The seroprevalence of HSV-2 in the US is 16.2% but women are at higher risk with a rate of 20.9%. The amazing fact is that only 19% of adults who are HSV-2 positive (and hence can spread the virus) are aware or their diagnosis! (I have frequently seen patients who come to my office with a complaint of “something down there” but deny any previous history of herpes…they may have had similar symptoms in the past but thought they were due to yeast infections or friction and never had these checked or diagnosed. Now… I am telling them that they have herpes. (And of course, the recriminations begin.) In most cases, especially if they are abstinent or have been with the same partner for years, it’s a recurrent infection. Remember that the virus can also be transmitted from the skin without a viable lesion. This is an STD that is chiefly spread without knowledge that it was there in the first place.

So what is the best way to diagnose HSV? When a “classic” group of vesicles (blisters) or ulcers occur, a culture of the lesions can be done. Especially in primary (first) infections, the culture will be positive in 48 to 72 hours. The sensitivity of the culture decreases the longer the lesion has been present. A positive culture is evidence of herpes, but a negative one doesn’t mean it’s not there, it simply means it was too late to find it or that the culture wasn’t sensitive enough. So ultimately the way to definitively diagnosis herpes and to distinguish between types 1 and 2 is with antibody testing…in a blood test called HerpesSelect 1 and 2. It can usually detect antibodies within 2 to 3 weeks of infection.

The treatment is usually oral with an antiviral medication. The generic and oldest form of medication is acyclovir. The dose for a primary infection is 400mg tablets three times a day for 7 to 10 days. There are 2 other antiviral medications that have somewhat better absorption and longer half-lives than acyclovir but essentially are converted to the same substance in the body. These are valcyclovir (Valtrex) and famcyclovir (Famvir). These are generally more expensive. The dose for Valtrex in a primary infection is 1 g twice daily, again for 7 to 10 days.  For Famvir it’s also 1g twice daily…..in recurrent infections, less is needed (and works best if started with the very first sign of infection, such as local tingling or pain). Acyclovir is given in a dose of 400mg, 3 times a day for 5 days, Valtrex, 500mg, twice a day for 3 days and Famvir two tabs of 500mg twice a day for just one day. And for suppression (it’s not complete but may decrease viral shedding and transmission to a partner) the prescribed dose is 500 mg of Valtrex daily or 250 mg of Famvir twice daily.  (I know this is getting very specific, but so many women ask for prescriptions, I thought I should include dosing.)

What should be done if herpes occurs during pregnancy?  How great is the risk for neonatal infection? About 1200 to 1500 babies are born in the US each year with neonatal herpes. The most likely cause for their infection is through contact with the active virus in the lower maternal genital tract during vaginal delivery. The majority of the infected babies are born to women who had no history of HSV infection (i.e. they acquired a new infection before delivery) and one third of the cases are caused by HSV-1. Only 3% of the infections are among women with recurrent clinically evident HSV-2 infection. A primary genital herpes outbreak is associated with a higher risk of perinatal transmission than a recurrent outbreak, presumably because the mother has no preformed antibodies that are transferred to the fetus. Neonatal herpes can be serious; 30% of seriously infected babies die and up to 40% of survivors have serious neurological problems. In the past, many women underwent C-section just because they had a history of herpes even though they didn’t have any active lesions at the time of delivery. (This falls into to the “you never know, let’s be safe” category.) But it’s the women who are seronegative (have no antibodies) and who get infected in the last trimester that are the most likely to pass the virus to the baby during delivery. Nor is it completely “safe” for women with active vaginal lesions to deliver vaginally. The current recommendations are:

During pregnancy all symptomatic infections (primary or recurrent) should be treated with a 7-day course of antiviral medication.
All women who have had recurrent herpes or a new infection in pregnancy should be given prophylactic antiviral medication beginning at 36 weeks (And if at risk for a preterm delivery, this should be started earlier.)
C-section is indicated in any women with active perineal (in and around the vagina and labia) lesions or prodromal symptoms (sense that a herpes lesion is starting).
C-section is not indicated in women with a history of HSV without active lesions or symptoms at the time of labor,
C-section is not indicated for nongenital lesions (if there is a lesion on the thigh or buttock in can just be covered with a bandage.)
Bottom line: Many of us have herpes. No, we don’t have a vaccine but short courses of antiviral therapy or daily medication will help diminish recurrence of lesions and spread of the virus.  Recurrences should be treated during pregnancy and at 36 weeks prophylactic antiviral medication may help prevent the need for C-section. If, however, an active lesion is present at time of labor, C-section is advised.

By now most of you have probably heard that ACOG (The American College of Obstetricians and Gynecologists) has made new recommendations as to how often and when to start doing Pap smears. Despite the timing, I don’t feel these are either economically or politically inspired by the currently debate on health care reform. The reasons behind these new recommendations are scientifically sound. I would like to share some of them with you…

It’s extremely difficult for women to reconsider their Pap priorities; after all we have been told for decades that we must have a yearly Pap smear. Indeed we were lead to believe that the Pap was the foremost reason to visit our gynecologist. (When I went to work in Israel after finishing my residency in the US, I tried to explain the importance of Pap smears. My colleagues and residents were puzzled…they had seen very few cases of cervical cancer and thought it only occurred in women with uncircumcised partners…. I’m not sure why it was uncommon, perhaps at the time the population was more monogamous. But a sexually active circumcised penis can spread the viruses that lead to cervical cancer as well as one that is “uncut”. Today Israeli gynecologists routinely do Pap smears. If you continue to read below however, you will see that “routine” has changed for everyone.) But I digress…

Many women believe that the Pap smear can, in its mythological and histological wonder, pick up every type of cancer “down there” including endometrial and ovarian cancer. Unfortunately, it usually won’t. The Pap can detect cells that herald the presence of cervical precancer and cancer caused by sexually transmitted HPV (human papilloma) viruses. There are more than 100 types of these ubiquitous HPV’s. They are all very contagious and easily transmitted during sexual intercourse. At least eighteen of them are deemed high risk. The high risk HPV’s are oncogenic agents which, if not cleared by the immune system, can enter the DNA and cause mutations in the cells of the cervix. These mutations can lead to the development of a precancerous lesion termed high grade squamous intraepithelial lesion or HSL and in turn this can go on to become invasive cancer.

Although an astounding proportion of young women (50 to 70%) are found to have HPV present in their cervix within 2 to 3 years of onset of intercourse, the majority have an immune response that is strong enough to clear the viruses within 8 to 24 months. Before they do, however, they may develop minor or low grade squamous intraepithelial lesions (LSL) that can then appear as an abnormality in a Pap smear. But as the virus is cleared, so usually is the low grade lesion. Patience is all that is needed to “cure” most of the early changes (termed dysplasia) caused by HPV in these young women.

Until recently doctors responded to mild and moderate Pap abnormalities in a sexually active adolescent or young woman with immediate reaction and action….we notified her that there was something “off” in the Pap smear and further testing was needed. (And she then called her Mom who invariably became hysterical.) We did colposcopy (an exam of the cervix with a microscope) and often followed this with biopsies. Then if the latter confirmed even mild changes we were taught to “catch and treat” immediately. We froze the offending cervix with cryotherapy to destroy the superficial “bad” cells or tried to destroy them with laser. (None of this killed the offending virus….we were treating the result not the cause.) And if the cells showed a more worrisome lesion we removed a part of the cervix with a procedure termed a LEEP or did a cone excision.

Well it turns out that early treatment in very young women was, in many cases, unnecessarily aggressive and harmful. The treatment could scar the cervix and lead to problems getting pregnant, maintaining a pregnancy to term (i.e. cause premature labor) and finally increase the risk of cesarean section.

Research on sexually active young women to see “what would happen if we left these early lesions alone” has shown that invariably the lesions do clear. Hence ACOG now recommends that gynecologists begin performing Pap smears in all women at the age of 21. The risk of missing a serious lesion in sexually active young women and adolescents is estimated to be 1-2 cases in a million. If Pap smears were done earlier, tens of thousands of minimally abnormal changes would be found and result in unnecessary procedures that could harm the future fertility and pregnancy in these young women.

ACOG also addressed the frequency of Pap smears in women who are older… No one wants to ignore the harm that high risk and non-cleared HPV’s can do over time. Hence the organization recommends Pap smears be performed every 2 years in women ages 21 to 29. And for women over 30, they feel it is probably sufficient to do the Pap smear every 3 years. (These women should already have a Pap history and are more likely to be in a mutually monogamous relationship.) To qualify for the 3 year rule a woman over 30 should have had 3 negative Pap’s. And negative Pap smears are most reassuring if HPV testing is also negative. (Note, I routinely order HPV testing in my patients when I do their Pap.)

Exceptions are made and Pap testing should be done more frequently for women over the age of 21 if they are immunocompromised, have been HIV infected, were treated for CIN2 or CIN 3 (high grade lesions) in the past or are DES exposed (their mother took DES while pregnant).

Remember if you are not in this risk group, if your Pap smears have been normal for many years, you do not have HPV and you are in a mutually monogamous relationship, nor have you had HPV in the past….you are not going to get cervical cancer unless you have a new “source” of HPV!

When it comes to stopping Pap smear testing….it’s a bit more complicated. Women aged 65 and older represent 14.3 % of the US population and have 19.5% of new cases of cervical cancer. In white women in the US the rates of new-onset of cervical cancer peaks in the 5th decade of life then decreases, in Hispanic women it is in the early 70’s and in Asian and Pacific Island ethnicity the incidence peaks in the late 70’s. The American Cancer Society recommends discontinuing Pap smears at 70; the US Preventive task Force has set the age at 65. ACOG suggests that if a woman over 65 is sexually active, and has more than one partner that she is still at risk and should get Pap smears. (Albeit she is less at risk than a younger woman because her cervical cells have undergone changes that make them less accessible to HPV caused mutations.) And women with a past history of abnormal Pap’s should continue screening until results are negative for 10 years.

Finally what about the women who have had a hysterectomy? If the cervix was not removed (a subtotal hysterectomy) you still need Pap smears with the same frequency as a woman who had not had this surgery. If however, the cervix was removed during the procedure (a total hysterectomy), then the only reason to continue having Pap smears is if the hysterectomy was done for a cervical high grade lesion or cancer. In this case the Pap can check for recurrence of the lesion in the vaginal cuff.

I know this all seems complicated. What I want to emphasize is that less frequent Pap smears does not mean less frequent pelvic, breast, or general exams. You will still receive annual reminders to come to see me (or whomever you go to for your gynecologic care). At that time we can discuss how often your Pap smear should be done. The rest of your exam can ascertain possible pathology in your breasts, uterus, endometrium, ovaries and hormones as well as any issues related to your general health (weight gain, diabetes, coronary vascular risk, hypertension, and bladder problems to name a few).
Women younger than 21 still need to discuss contraception, and if sexually active should be checked for STD’s, and taught how to prevent them. And if any woman has menstrual problems she should seek diagnosis and treatment. Women who plan to conceive should be seen and given appropriate preconception tests and advice.

The era of reproductive health sets the status for our entire lives. Once we enter menopause there are many more health and well-being issues we have to deal with. (Please note I haven’t even begun to talk about hormonal issues.) The cervix is just one part of our reproductive system. Pap smears save lives….but we are more than a cervix and need to maintain the health of the rest of our body.

We could ask our kids (rarely works), speak to the school administrators (they are probably the last to know),  read Seventeen and Cosmo or just look with despair at the promiscuous styles offered to and requested by young girls (and boys).

In my perusal of journals, I found a fascinating study which addresses this question. It comes from the National Youth Risk Behavior Survey conducted from 1999 though 2007. (Remember it takes a year or two to collect, analyze and publish information of this sort, hence it did not include ‘08 and ‘09.) Researches analyzed data from this survey to determine age at first intercourse in 66,882 black, Latino and Latina, white and Asian students in grades 9 though 12. According to the students’ anonymous self reports, the probability for “coital debut” by their 17th birthday (I’m assuming they meant vaginal intercourse, the use of euphemisms in medical reportage is astounding!) was: 82% for black males, 74% for black females, 69% for Latinos, 59% for Latinas, 53% for white males, 58% for white females, 33% for Asian males and 28% for Asian females

Now before we take this report and approach our children or grandchildren with queries as to whether they fall into the above listed statistics (“did you or didn’t you?”), I should point out that the survey was based on self-reported data. Girls are more likely to underreport sexual activity, whereas boys tend to over report. The survey did not stratify the groups by parental income or educational level, nor did it differentiate between public or private school attendance. And the study did not include youths who had dropped out of school (who would, most likely, skew early coital debut to higher probability).

I realize that parents don’t always like to look at gross statistics when it comes to their own progeny. But this large study does show us that a majority of teens self report that they were sexually active before the age of 17. It’s way better than rumors… and should help parents decide when to make sure that their daughters have access to appropriate contraception. (This may have the appearance of a plug for Planned Parenthood and I should disclose that in the past I was on the board of the LA chapter of this organization). We know that timing is important for HPV vaccination. The best results will be achieved if the vaccine is given before a girl becomes sexually active. Hence most pediatricians now discuss this with parents at a time when they are not quite ready to consider that their “little girl” will engage in sexual activity. But they will… Finally this survey emphasizes what we already know; all young teens should be taught about STD’s and the need for protection before they have that first, often too early, sexual encounter.