HPV and Cervical Cancer

by National Cancer Institute

Cervical infections due to a group of about 15 oncogenic, or cancer-causing, human papillomavirus (HPV) types cause virtually all cervical cancers. They also are the cause of their immediate precursor, cervical intraepithelial neoplasia grade 3 (CIN3), a precancerous condition. Overall, about 10 percent of women at any one time have an oncogenic HPV infection, and they are more common in young women than in older women. Most cervical infections by even oncogenic HPV types go away on their own and do not cause cancer. In some women, oncogenic HPV infections persist and can progress over several years to CIN3, and may even progress to invasive cervical cancer. Most women, however do not progress to the precancer stage. Cervical cancer itself is extremely rare in the United States; there are about 11,000 new cases diagnosed and about 4,000 related deaths reported annually.

Understanding Pap Smears and Other Cervical Cancer Screening and Management Techniques

1. What is a Pap smear? What is a colposcopy?

A Pap smear is a procedure in which cells are scraped from the cervix (the lower, narrow end of the uterus that serves as a channel between the uterus and the vagina) and examined under a microscope. A Pap smear is used to detect cancer and cellular changes that may lead to cancer, as well as non-cancerous conditions like infection or inflammation.

A colposcopy is a procedure in which the vagina and cervix are examined using a lighted magnifying instrument called a colposcope. The vagina and cervix may be biopsied during a colposcopy so that tissue samples can be examined under a microscope for abnormal cells. A colposcopy may be prescribed if a Pap smear detects certain abnormal cellular conditions.

2. What is human papillomavirus (HPV)?

There are more than 100 types of human papillomaviruses (HPV). HPV is one of the most common sexually transmitted diseases (STDs), and more than 30 of the different types of HPV can be transmitted through sexual contact. While some types of HPV may cause warts to appear around the genitals, HPV infections also may occur without any obvious symptoms.

The U.S. Food and Drug Administration (FDA) has approved the use of a test for HPV as a screening tool for cervical cancer in conjunction with a Pap smear or cytology. Oncogenic HPV DNA testing (or "triage") for patients with ASCUS has proven to be a useful alternative to referring patients for immediate colposcopy to detect CIN3 and cancer (greater or equal to CIN3). A 2004 conference of the International Agency for Research on Cancer concluded that there was sufficient evidence that HPV DNA testing could be used as a primary screening test in women age 30 and older.

3. Why are HPV16 and HPV18 important?

Of the types of HPV that increase risk for certain types of cancer, HPV16 is the most common among women in the general population. Large case studies have shown that approximately 50 percent of women with CIN3 or cervical cancer are infected with HPV16. Additional research suggests that 60 percent to 70 percent of cervical cancer cases worldwide are caused by either HPV16 or HPV18. Virtually all remaining cases of cervical cancer are caused by other oncogenic HPV types.

4. What are ASCUS and LSIL?

ASCUS and LSIL are acronyms for two mild abnormalities detected by Pap tests. ASCUS stands for "Atypical Squamous Cells of Undetermined Significance", and LSIL stands for "Low-grade Squamous Intraepithelial Lesion".

A diagnosis of ASCUS means that the nature of the abnormality is uncertain or equivocal. A diagnosis of LSIL means that there is a more definite, but still mild, abnormality.

Study Findings

5. What were the goals of the ALTS and the Portland Kaiser Permanente studies?

The National Cancer Institute (NCI) organized and funded ALTS (the ASCUS/LSIL Triage Study for Cervical Cancer) to help resolve the controversy over what physicians and women should do about ASCUS (equivocal) and LSIL (mildly abnormal) Pap test results*. Most of these abnormalities will go away without treatment, but some may lead to a precancerous condition or cancer. This analysis of the ALTS data provided the opportunity for researchers to determine whether women with equivocal Pap smear results, who also tested positive for HPV16, had a greater risk for CIN3 or cervical cancer than women with equivocal Pap smear results who tested positive for other oncogenic types of HPV.

The Portland study was designed to examine the natural history of HPV infection and cervical neoplasia (abnormal and uncontrolled cell growth)**. Additionally, this study allowed analysis of whether testing specifically for HPV16 and HPV18, in addition to overall testing for all HPV oncogenic types, might help identify women at particularly high risk for CIN3 or cervical cancer.

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