The human papillomavirus

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Each year more than 13,000 women are diagnosed with cervical cancer in the United States. In most cases cervical cancer can be prevented if detected early and abnormal cell changes can be treated. We now know that these changes are caused by Human Papillomavirus also known as HPV which is the most common sexually transmitted infection. The HPV family of viruses is called papillomavirus because they cause warts, or papillomas - benign tumors. In fact, most man and woman are infected with HPV at some time in their lives. There are approximately 100 types of HPV. [1] Some HPV types only infect the genital area and may cause warts, some cause mild changes in cervical cells that do not turn into cancer, and some cause changes that may become cervical cancer if present for many years. The types of HPV that are found in the genital areas are normally passed on during sexual contact and do not spread outside of the genital area. Most infected persons do not realize they are infected or that they are passing the virus on to a sex partner. More than 30 strains are called genital strains which are spread through sexual contact and only 15 are associated with cervical cancer. These are called high-risk strains (HPV 16 and 18 cause 70 percent of cancers) as described at Two low-risk strains of HPV-HPV6 and 11 cause 90 percent of genital warts but they have no risk of causing cervical cancer.[2]

HPV can cause normal cells on infected skin to turn abnormal. Most of the time, you cannot see or feel these cell changes. In most cases, the body fights off HPV naturally and the infected cells then go back to normal. But in cases when the body does not fight off the infection, HPV can cause visible changes in the form of genital warts. Warts can appear within weeks of months after getting infected with HPV.

In almost all cases, the body's immune system will keep the virus under control or get rid of it completely. However, if HPV infection does not go way over many years, there is a greater chance of developing cell changes that may lead to cervical cancer. Cervical cancer usually does not have symptoms until it is quite advanced. That is why it is extremely important for women to get regular screening for cervical cancer. Screening tests can find early signs for disease so that problems can be treated early, before they ever turn into cancer.

There are several ways that people can lower their chances of getting HPV. Vaccines can protect both males and females against some but not all types of HPV infections. The vaccine is given in three doses and it is extremely important to get all doses to get the best protection. It is recommended to get vaccinated before a person's first sexual contact before he or she could get infected with HPV. There are two vaccines currently on the market that protect females from the type of HPV that cause most cervical cancer are Cervarix and Gardasil. Only one vaccine is available for males that protects against most genital warts is Gardasil. [3]

Cervical Cancer

Approximately 90% of cervical cancers are squamous cell carcinomas. This type of cancer originates in the thin, flat, squamous cells on the surface of the ectocervix, the part of the cervix that is next to the vagina. Another 10% of cervical cancers are of the adenocarcinoma type. This cancer originates in the mucus-producing cells of the inner or endocervix, near the body of the uterus. In some cases the cancer may have characteristics of both types and is called adenosquamous carcinoma or mixed carcinoma.[4]

The initial changes that may occur in some cervical cells are not cancerous. However, these precancerous cells form a lesion called dysplasia or a squamous intraepithelial lesion (SIL), since it occurs within the epithelial or outer layer of cells. These abnormal cells can also be described as cervical intraepithelial neoplasi (CIN). Moderate to severe dysplasia may be called carcinoma in situ or non-invasive cervical cancer. Dysplasia is a common condition and the abnormal cells often disappear without treatment. However, these precancerous cells can become cancerous if patients are not compliant with follow up procedures. It could take years for abnormal cells to become cancerous. Eventually, they start to grow uncontrollably into the deeper layers of the cervix, becoming an invasive cervical cancer.

Clinical trials have shown that the vaccine is safe and 100 percent effective in preventing HPV strains 16 and 18. However, it does not protect against all strains so the FDA recommends continuing screening with regular Pap test routinely. In conjunction with the Pap test, the HPV test, which uses DNA-based Hybrid Capture 2 technology to detect HPV, can be used in women to help detect HPV infection. [5]


The Papanicolau (Pap) smear has been the most effective screening method developed in the prevention of cancer since 1941. [6] The cervical smear was introduced by the Greek-American pathologist George Papanicolau (1883-1962). The Pap test is a procedure that is performed by your physician in which cells from the cervix or vagina a scraped to check for cervical cancer, vaginal cancer, or abnormal cell growth that could lead to cancer. The Pap test can occasionally detect endometrial (uterine) cancer or ovarian cancer; however it was not designed for that purpose. Women should begin to have Pap test at the age of 21 or within three years of becoming sexually active, whichever comes first. Young people are more likely to have multiple sex partners; therefore it increases the risk of certain diseases that could cause cancer such as Human Papillomavirus (HPV).[7]

Molecular tests can be used to detect HPV DNA. The only test that is currently approved by FDA is Digene's Hybrid Capture II HPV Test, a solution hybridization method to test for high-risk HPV DNA. Samples that can be tested with this technology include exfoliated cervical cells collected with a specially designed brush and placed into a liquid medium or in residual fluid left over from liquid-based cytology specimens. This HPV DNA test is designed to detect high-risk types of HPV (types 16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59, and 68). The HPV DNA test detects whether one or more types of HPV are present, it does not identify individual HPV types. The main point of this test is to identify women with high-risk HPV who are at risk of having or developing pre-cancerous or cancerous changes in the 36 months following initial testing. [8]

There has been a numerous research conducted in the importance of both screening methods. For this particular reason we're going to review a randomized trial that compared the two methods to determine whether testing for DNA of oncogenic human papillomaviruses (HPV) is superior to the Papanicolau (Pap) test for cervical cancer screening.

Human Papillomavirus DNA versus Papanicolaou Screening Test for Cevical Cancer study was designed by Marie-Helen Mayrand, M.D., Eliane Duarte-Franco, M.D., Isabel Rodrigues, M.D., Stephen D. Walter, Ph.D., Alex Ferenczy, M.D., Sam Ratnam, Ph.D., Francois Coutlee, M.D., and Eduardo L. Franco, Dr.P.H.


Researchers compared HPV testing using an assay approved by the Food and Drug Administration, with conventional Pap testing as a screening method to identify high-grade cervical intraepithelial neoplasia in women ages 30 to 69 years. Women with abnormal Pap test results or a positive HPV test underwent colposcopy and biopsy, as did a random sample of women with negative tests. The participants were randomly assigned to "focus on Pap" or a "focus on HPV" screening group. In the "focus on Pap" group, the women received a Pap test first, whereas in the "focus on HPV" group, the women received an HPV test first, the tests were performed sequentially at the same visit. Participants were referred for colposcopy if they had a positive Pap or HPV screening test or if they were randomly selected from among women with a negative index test. Patients underwent a biopsy first and were treated with a LEEP or cold-knife conization procedure.

High-grade cervical intraepithelial neoplasia is the accepted end point for cervical screening and an actionable finding for clinical management of the disease. Researchers used two case definitions: conservative and liberal. The liberal definition included all cases of grade 2 or 3 cervical intraepithelial neoplasia, adenocarcinoma in situ, or cervical cancers that were histologically confirmed on the basis of any of the histologic specimens. Conservatively defined cases were those that met the liberal criteria and that in addition were confirmed in the LEEP specimen or by a confirmatory biopsy in the base of ablative treatment.

The data were divided into strata of combined Pap and HPV test results. Disease prevalence in each stratum was assumed to be independent of whether the women underwent biopsy. Stratum-specific probabilities were then applied to the remainder of the women who had not undergone biopsy, which permitted an estimate of the number of cases that would have been found if all study participants had undergone histologic verification. Corrected sensitivity and specificity estimates were then calculated, and 95% confidence intervals were computed by the method described by Zhou. A z-test was performed on the differences between the sensitivity and specificity of the HPV and Pap test.


A total of 10,154 women were randomly assigned to testing. Both tests were performed on all women in a randomly assigned sequence at the same session. The sensitivity of HPV testing for cervical intraepithelial neoplasia of grade 2 or 3 was 94.6%, whereas the sensitivity of Pap testing was 55.4%. The specificity was 94.1% for HPV testing and 96.8% for Pap testing. Performance was unaffected by the sequence of the tests. The sensitivity of both tests used together was 100%, and the specificity was 92.5%. Triage procedures for Pap or HPV testing resulted in fewer referrals for colposcopy than did either test alone but were less sensitive.


As compared with Pap testing, HPV testing has greater sensitivity for the detection of cervical intraepithelial neoplasia. In settings with quality assurance for screening, diagnostic, and therapeutic procedures, it is difficult to predict whether a change from Pap testing to HPV testing will further reduce the rates of death from cervical cancer. For women who are screened less frequently than recommended, a more sensitive test, such as the HPV test, may prove important. The incorporation of HPV testing into primary screening will require the education of patients. As described in the study, a shift from cellular to viral tests, coupled with education and vaccination, will contribute to a more efficient control of cervical cancer. [9]


  1. American Society for Colpposcopy and Cervical Pathology (
  2. Healthy Women (
  3. Center for Disease Control and Prevention (
  4. The Gale Encyclopedia of Medicine. Lata Cherath and Margaret Alic. Cervical Cancer. Ed. Deirdre S. Blanchfield and Jacqueline L. longe. Vol. 2. 2nd ed. Detroit: Gale, 2002. p711-717
  5. Encyclopedia of Public Health. Thomas J. Rutherford. Cervical Cancer. Ed. Lester Breslow. Vol. 1. New York: Macmillan Reference USA, 2002. p177-178
  6. Encyclopedia of Public Health. Thomas J. Rutherford. Pap Smear. ED. Lester Breslow. Vol. 3. New York: Macmillan Reference USA, 2002. p888-889
  7. Medicine, Health, and Bioethics: Essential Primary Sources. Ed. K. Lee Lerner and Brenda Wilmoth Lerner. A Revised System for Reporting Pap Test Results. Detroit: Gale, 2006. p155-159
  8. Human Papillomavirus: HPV Information for Clinicians. Center for Disease Control and Prevention. April 2007. p13-19 (
  9. Marie-Helen Mayrand, M.D., Eliane Duarte-Franco, M.D., Isabel Rodrigues, M.D., Stephen D. Walter, Ph.D., Alex Ferenczy, M.D., Sam Ratnam, Ph.D., Francois Coutlee, M.D., and Eduardo L. Franco, Dr.P.H. Human Papillomavirus DNA versus Papanicolaou Screening Tests for Cevical Cancer. October 18, 2007. The New England Journal of Medicine. Vol. 357. No. 16