Dr. Anna Priebe explains HPV and how it causes cervical cancer

Cervical cancer screening is one of the most successful cancer screening programs ever devised. Since the adoption of the Papanicolau (Pap) test in the 1960s, rates of cervical cancer in the United States have decreased by 75 percent. Currently, the American Cancer Society estimates that approximately 12,000 women in the U.S. were diagnosed with cervical cancer in 2012. Compare that to the mind-boggling 500,000 new cases of cervical cancer diagnosed worldwide each year. Pap smears work. But more on that later.

What is cervical cancer?

So, before we get into cervical cancer, what is a cervix anyway? The uterus and cervix are actually parts of the same physical structure, shaped much like a light bulb or an upside down pear. The glass portion of the light bulb is called the uterus and the silver/metal part corresponds to the cervix. Together, they make up one organ but are made of different "stuff" and have very different jobs.

The cervix is thick and fibrous with a central canal leading into the uterine cavity. It functions as the plug that keeps a pregnancy inside the uterus and, during labor, dilates to allow the fetus to exit the uterus. The cervix is lined by two types of cells—squamous cells, which cover the outer part of the cervix, and glandular cells, which line the canal leading into the uterus. Each of these cell types can give rise to cervical cancer. The squamous cells give rise to squamous cell carcinomas and the glandular cells to adenocarcinomas.

All cervical cancer is caused by persistent infection with the human papillomavirus (HPV). Now, let's just get this part out of the way—just about everyone who has ever had any sort of sexual contact has been exposed to HPV. Not just intercourse—any sexual contact. This pretty much ensures that the majority of the population has been exposed. HPV is the most common sexually transmitted infection in the U.S. While there are more than 100 different HPV types, only about 15 are capable of causing cancer—these are termed “high-risk HPV” or “oncogenic HPV.” Of these high-risk HPV, two types—HPV 16 and HPV 18—are responsible for the vast majority of cervical cancers.

HPV infections are most common around the time of first sexual intercourse and the few years thereafter. This makes sense, as sexual contact is the vehicle for HPV transmission and, statistically, the late teens and early 20s are prime years for sexual activity. Studies show that about 25 percent of 14-19 year olds and 45 percent of 20-24 year olds are infected with HPV at any given time. About a third of the time, they are infected with more than one strain of HPV. Generally, these new infections are cleared by our immune systems, with 90 percent of women clearing their infections within two years.

The small number of women with persistent HPV infection are at highest risk for the development of cervical cancer. When HPV infects a cell, it hijacks its internal machinery, diverting it from making things for itself to making more of the virus. Sometimes, the viral DNA can actually insert itself into the cell's own DNA, becoming a permanent part of that cell and all of its descendants.

Normal cells have a tightly regulated life cycle with several checks on their ability to divide and replicate. They divide in an orderly, organized fashion and respect their fellow cells, such that, when they come into contact with a neighbor cell, they stop growing. This allows for entire communities of cells to live and work together in harmony, forming tissues and organs to carry out the functions of the body. HPV infection disables these normal checks and balances and causes cells to divide continuously. In order to divide, cells must make a copy of their DNA, so a set can go into each daughter cell. DNA copying is not a perfect process and mistakes can be made. Our cells normally have repair enzymes that go along and check the DNA, detecting errors that may have occurred. If an error is found, it is either repaired or the cell is slated for self-destruction, called “apoptosis.” HPV disables the cell's ability to activate this self-destruct cycle. So we have cells that have been taken over by HPV and are forced to continuously divide all the while DNA errors, called “mutations," accumulate and persist, as the cell is unable to enact its self-destruct sequence. Mutations can be either good or bad for a cell. Sometimes they will cripple a cell by affecting a process critical to cell function. Other times, mutations can confer superpowers on a cell, allowing it to live and grow in conditions not possible for a normal cell, to use food sources it normally cannot use, to escape the confines of its cellular programming and the to invade other tissues.

The effects of HPV infection can be seen under the microscope. When HPV changes can be seen throughout the entire cell layer, this is termed high-grade dysplasia. Left alone, high-grade dysplasia will eventually turn into cervical cancer.

Cervical cancer is highly preventable.

The process of HPV infection and the progression of a persistently infected population of cells to high-grade dysplasia and, finally, to invasive cancer, takes an average of 10-15 years. Thus we have a long time in which to prevent cancer.

Screening tests have been successful both in decreasing rates of cervical cancer as well as improving the overall survival of women with cervical cancer for the following reasons:

1)     They are able to pick up abnormal cells in the cervix before they turn into cancer.

2)     They enable us to find cervical cancers while they are small and early stage. When cervical cancer is found early, it is highly treatable and associated with long survival.

The Pap smear samples squamous and endocervical cells which are then examined under a microscope for signs of HPV infection. If suspicious cells are found, the cervix must be examined and biopsies taken to detect the presence of precancerous high-grade dysplasia.

Having said that, the Pap smear is not a perfect test. The accuracy of a single Pap test is actually only about 50-80 percent. The success of the Pap smear lies in serial testing, meaning that several normal Paps in a row are very reassuring that there are no abnormalities. Over 50 percent of cervical cancers in the US are diagnosed in women who are rarely or never screened for cancer, and another 10–20 percent of cancers occur among women who were screened but did not receive adequate follow-up care.

Since persistent HPV infection is the cause of virtually all cervical cancer, testing for infection with high-risk HPV types provides a lot of information about an individual patient's risk of abnormal cells and cervical cancer. Testing negative for high-risk HPV is very reassuring that no dysplasia or cancer is present.

Currently, women should start getting Pap tests at age 21 and thereafter, every three years. Women who are 30 years of age or older may have an HPV test along with the Pap test. If both tests are normal, testing may not be needed for five years. Once a woman turns 65, if she has had regular, normal Pap smears, screening may be discontinued.

Again, since HPV is responsible for the vast majority of cervical cancers, preventing HPV infection should prevent the development of cervical cancer. In the last 10 years, vaccines against the HPV virus have become available. Vaccination is recommended for girls and boys, starting at 11-12 years old. It's important to note that the vaccines protect against only the most common high-risk HPV types (which account for the majority of cervical cancers). Therefore, vaccinated women still need to be screened for cervical cancer. As more and more of the population is vaccinated, we would expect less HPV related disease, necessitating reevaluation and revision of the current screening guidelines.