HPV Type Associated with Cancer

Frederick R. Jelovsek MD

"I would like to know how accurate the tests are that are out right now for the different strains of HPV. I would like to have the test done if I thought it was reliable in diagnosing if I have the type(s) that is thought to lead to cervical cancer. I am very concerned about HPV and treatments and how from what I have heard that the treatments are not very successful. Do you know?

I am 32 years old, married with one child. I have a regular cycle and was recently told from a biopsy that the lab suspects that I have HPV due to the abnormal results. No medications. ". 

Exposure to human papilloma virus (HPV) can be measured by testing the blood (serum) for antibodies to the viral capsule or by testing actual tissue such as cells from a Pap smear or tissue from a biopsy for viral DNA fragments. This latter test is known as Viratype. It is more commercially available than the blood antibody testing, but this is a rapidly changing field so you must check as to which tests are locally available.

There have been many different HPV types described. Some are more often associated with cervical cancer or vulvar cancer while other types are more common with benign epithelial lesions such as condyloma accuminata or venereal warts. Having been exposed to one virus type does not prevent getting infection from another virus type. In fact one study looking at seropositivity to HPV type 16 found a 30% incidence of multiple HPV type positivity (1). Patients and doctors alike have difficulty keeping up with this field so let's look at some of the different aspects of HPV.

Which types of HPV are most associated with cancer?

Certain viral subtypes of HPV are much more commonly associated with cancer than other subtypes. The best known of these HPV types are 16, 18, 31, 33, 39, 45, 52, and 58 (2). Type 16 is the most common but it still is not the most frequent type. Types 16 and 18 are the major risk factors for cervical carcinoma, whereas HPV types 6 and 11 cause benign genital lesions.

Over 90 different subtypes of HPV have been described. As you can see it is difficult to test for all of those different subtypes. Sometimes a test is made to screen for 4 or 5 of the most common types but by definition it will not be accurate to pick up all possible HPV infections. This is true for both for tissue DNA typing and blood antibodies.

How accurate is the test on tissue cells to identify HPV infection and type?

Since any test for HPV subtype is limited to only that subtype or group of subtypes, it will miss a certain number of HPV infections. The combinations that have been screened for often include the most common types associated with malignancy. No one knows what other types will be missed so it is only a guess as to how accurate a test is. In general, positives are positive, i.e., there are very few false positive tests. If you are tested positive for say type 16, 18 HPV, then that result is probably 95% certain. The opposite is not true, however. If the test is negative, you could have been exposed to some other type.

The main use of HPV tissue DNA fragment testing has been in uncertain PAp smear results such as the atypical squamous cells of uncertain significance (ASCUS). In this strategy, women with ASCUS Paps which are just usually repeated at 3-4 months, could be tested and if positive for HPV 16, 18 etc., then they could be referred to colposcopy and would have a higher chance of having cervical precancerous changes called dysplasia. Thus if tissue HPV typing is unavailable from your doctor or in your area, having a colposcopy and biopsy would reassure whether or not you have dysplasia which the Pap missed. If the colposcopy is negative, then there would be no treatment even if the HPV test were positive. If the colposcopy and biopsy are positive for dysplasia, then whether the HPV test showed a type associated with cancer would not make a difference in the treatment.

What do the blood tests for antibodies to HPV mean?

Antibodies, especially those called IgG antibodies, are manufactured by the body for a very long time after exposure to HPV. Gradually, over decades they may lessen in amount to undetectable levels, but they may also increase with each repeat exposure. The antibodies indicate exposure in the past to HPV and since the virus particles can stay forever in tissue, it very likely means there are some virus cells of that type still present in the body somewhere.

A positive blood titer for an HPV type only means exposure at sometime in the past. It does not necessarily mean that a current abnormal Pap is due to the type although it may be. Also, if 60-70% of adult females have positive titers to the high risk HPV types, it is almost impossible to know what action to take if your titer is positive except that you need to have regular, periodic Paps and check-ups.

Is HPV always a sexually transmitted disease?

HPV is very frequently transmitted sexually and often explains why dysplasia of the cervix is considered a sexually transmitted disease (3). It is important to understand that is is not always sexually transmitted. In fact children can be positive for HPV antibodies with a background incidence of 3% (4) while 60-70% of adults will show antibodies to HPV types 16, 18 and 33. Since only a few percent of the population ever develops cervical cancer, HPV is not a direct cause and effect.

While not necessarily conclusive that HPV can be transmitted non sexually except during the birth process, women who have never had sex with men, but only with other women can also be positive for HPV (5).

What should I do if I have a biopsy or Pap smear suggestive of HPV?

Options for this situation include:

• No further studies except follow-up Paps according to standard follow-up
• Have the biopsy tissue or Pap cells tested for virus subtype and if positive for a high risk type, treat mild dysplasia more aggressively with excision or destruction rather than just following to see if it resolves on its own.
• have your antibody titers checked and if negative for a high risk HPV type, just continue with annual Paps and check-ups and not a lot of extra visits for repeat Paps

There is no medical treatment for HPV. The only treatment is to remove cells in which the virus has caused some visible changes. The virus lies dormant in many cells, however, so there no way to totally rid the body of the virus or at least to be sure that you have excised all affected cells.

The important concept with HPV is not to become overly concerned about having manifestations of the virus. There is no way that a reasonable person in this day and age should have a cervical cancer develop. they just need to have periodic Pap smears and pelvic exams. Because you have just found out you have HPV cervical changes does not mean your partner has been unfaithful. You could have contracted the virus at any time you ever had sexual relations or so could your partner before meeting you. You or your partner may even have been part of the 3% of people who were positive for HPV from childhood. Try not to despair and panic about this. There are hundreds, if not more, of "incurable" viruses you have been exposed to during your life up to this point and more yet to come. So just be careful and vigilant.

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