Update on Cervical Cancer

In the United States, cancer of the cervix was once the most common type of cancer afflicting women.¹ And globally, it remains a lethal disease.However, a half-century of aggressive education campaigns and regular testing regimens in the U.S., combined with several recent technological advances in treatment and prevention, have resulted in a much lower rate of cervical cancer among American women than in previous generations. In fact, cervical cancer has decreased by 74 percent since 1955 and now represents less than 1 percent of all cancer diagnoses in the United States.² Today, American women who do develop a cervical cancer are far more likely to receive successful treatment and survive today, with death rates from cervical cancer continuing to decline at around 4 percent per year.³

Even with the relatively good news regarding modern medicine’s ability to prevent and successfully treat cervical cancer, the sobering reality is that in 2010 (the most recent year for which statistics were available at press time), roughly 12,000 women in the U.S. were diagnosed with cervical cancer, while just under 4,000 cases resulted in death.⁴ The World Health Organization estimates more than half a million women worldwide will develop cervical cancer this year.⁵

Even if it is no longer the killer it once was in the United States, a diagnosis of cervical cancer very much remains a tragedy for thousands of young women each year who see their dreams of starting or growing their families threatened, since cervical cancer and its treatments can leave a patient unable to bear children.

What Is Cervical Cancer?

The definition of “cervical cancer” is one based on the location of the growth; it is any malignancy that forms on the cervix.

The cervix is the connection between the uterus and the vagina. The lower portion of the cervix, nearest the vagina, is composed of squamous cells; the higher portion is made up of glandular cells. However, most cervical cancers arise in the transitional area, which is composed of both kinds. Malignancies of these two kinds of cells are responsible for nearly all cases of cervical cancer. Squamous cell carcinoma arises from abnormal squamous cells, while precancerous glandular cells can develop into adenocarcinoma. More than 80 percent of cervical cancer diagnoses are of squamous cell carcinoma, and both of these types of cervical cancer typically develop from earlier precancerous abnormalities.

In addition, other types of cancers, including melanoma, sarcoma and lymphoma, do sometimes arise in the cervix, although this happens rarely.⁶

Symptoms of Cervical Cancer

Abnormal precancerous cells rarely manifest any noticeable symptoms. Only after the abnormalities have become cancerous do most symptoms arise. These may include irregular bleeding (outside normal menstrual cycles or following sex), abnormal discharge, pain during sex or unexplained changes in the menstrual cycle.⁷

Because symptoms do not typically appear until the disease is advanced, regular testing for cervical precancer has been recommended for women beginning in their 30s since the 1950s. The Papanicolaou test, more commonly known as a Pap smear, is the most common screening method for abnormal cell changes in the cervix.⁸

Diagnosing Cervical Cancer

Regular use of the Pap smear as an integral component of women’s healthcare is primarily responsible for the massive decline in both cervical cancer cases and improved survival rates for those diagnosed. Yet, despite the decline, the American Congress of Obstetricians and Gynecologists (ACOG) issued new guidelines for cervical cancer screening in 2009, which resulted in a great deal of controversy in the medical community. ACOG’s new guidelines changed from a Pap smear annually at age 18 or three years after becoming sexually active to a Pap smear annually beginning at age 21; an annual Pap smear for women ages 21 through 29 to a Pap smear every two years; and a Pap smear for women over age 30 every two to three years to only every three years (with the addition of an HPV test done at the same time as an option) if they have had three consecutive negative Pap smear results.⁹

During a Pap smear, cells are collected from the outer opening of the cervix. These cells are examined microscopically to determine if any are exhibiting signs of precancerous changes.¹⁰ If any abnormalities are discovered, a more detailed examination is generally prescribed, including a biopsy, a visual examination or both.

Causes of Cervical Cancer

The vast majority of cervical cancer cases are caused by a strain of the human papillomavirus, or HPV. HPV is a sexually transmitted virus that is endemic among sexually active adults the world over.¹¹ It causes no symptoms of its own, and most women with HPV will not develop cervical cancer. Men with HPV most often exhibit no symptoms and typically have no idea they are infected.¹²

There are more than 150 strains of HPV, but four of them (types 16, 18, 31 and 45) are responsible for roughly 85 percent of cervical cancer cases. Other strains are also linked to cervical cancer (and yet others to genital warts in both men and women), and it is not unusual for sexually active adults to carry multiple strains without any symptoms.¹³

Other possible risk factors of cervical cancer include smoking, having multiple sexual partners, having HIV, giving birth three or more times or using oral contraceptives over a sustained period of time.¹⁴ As with all cancers, other triggers likely exist that are not yet discovered or fully understood.

Treating Cervical Cancer

Treatment depends on the stage of the cancer or precancerous abnormality that is discovered, and the age of the patient. For early or precancerous abnormalities, treatment generally consists of removing the abnormal or malignant tissue with electrical current (loop electrosurgical excision procedure, or LEEP) or laser, or freezing it to kill it.¹⁵

If the cancer is more advanced, then surgery is usually necessary to remove the cancer. The amount of tissue to be removed will depend on how far the cancer has spread, as well as the patient’s hope to bear children in the future.

Preventing Cervical Cancer

With the overwhelming number of cervical cancer cases tied to HPV, recent prevention efforts have focused on inoculating against the virus. Since the introduction of HPV vaccines, infections rates have dropped by almost 50 percent.¹⁶

There are three vaccines currently available to protect against HPV: Cervarix (GlaxoSmithKline), Gardasil (Merck) and, now, Gardasil 9 (Merck). All are available for girls and young women and are administered in three timed doses. Gardasil also protects males from an HPV infection, which can also help in stopping the spread of the virus to their partners,¹⁷ as well as protects against anal cancer, 92 percent of which is likely caused by HPV.¹⁸

These two vaccines have been effective, however, only against a handful of the more than 150 strains of HPV. Cervarix only protects against types 16 and 18.19 Gardasil protects against types 6, 11, 16 and 18. While strains 16 and 18 are responsible for most causes of cervical cancer, types 6 and 11 cause an estimated 90 percent of genital warts.²⁰ Fortunately, in December, the U.S. Food and Drug Administration approved Merck’s Gardasil 9, a 9-valent HPV vaccine for girls and young women ages 9 through 26 for prevention of cervical, vulvar, vaginal and anal cancers caused by HPV types 16, 18, 31, 33, 45, 52 and 58, pre-cancerous or dysplastic legions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58, and genital warts caused by HPV types 6 and 11. Gardasil 9 is also approved for boys 9 to 15 years of age for the prevention of anal cancer caused by HPV types 16, 18, 31, 33, 45, 52 and 58, precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58, and genital warts caused by HPV types 6 and 11. According to Dr. Julie Gerberding, president of Merck Vaccines, with Gardasil 9, “there is an extraordinary opportunity to even further reduce the burden of HPV-related diseases and cancers in males and females.”²¹

Each of these vaccines is most effective if administered before young people become sexually active and are thus exposed to HPV. They can be administered to adolescents beginning at age 9, although a window of 11 or 12 is recommended for the first dosage. However, as both vaccines inoculate against multiple strains of HPV, it is still recommended that women under the age of 26 and men under the age of 21 receive one of the vaccines. Even if young adults have been exposed to one strain, the inoculation offers the chance of building immunity to other types targeted by the vaccines.²²

Using condoms has not yet been proven to be 100 percent effective at stopping the spread of the HPV virus; however, other studies have indicated that women who regularly have their partners use a condom during sex have a lower risk for developing cervical cancer.

Ongoing Research

Given the debilitating nature of cervical cancer, threatening to rob patients of the ability to bear children or remain sexually active (depending on the severity of the case and the nature of the treatment), ongoing research into its prevention remains a high priority, despite the relatively low rate of incidence compared with other cancers.

There are some promising studies currently being conducted to not only provide more effective protection against acquiring HPV or developing cervical cancer, but also to help the patient’s body effectively fight a current case of cervical cancer or HPV infection. The American Cancer Society reports on a line of research to provide a vaccine to women already infected by HPV to help the body destroy the virus before it can cause cancer. Another promising line of research seeks to get the patient’s body to destroy specific proteins unique to HPV in order to stop healthy cervical cells from changing to abnormal precancerous cells.

Other studies include applying the antiviral drug cidofovir on precancerous areas to stop HPV from reproducing; the American Cancer Society reports an early test shows some success. Another antiviral drug, imiquimod, is also being tested to fight cervical cancer by fighting the type of HPV that causes most cases.

Besides inoculations and antivirals, targeted therapy drugs are also being explored in the fight against cervical cancer. The noted anti-cancer drug Avastin, which helps block the formation of new blood vessels — thus starving or at least slowing malignancies— has been effective in treating advanced cervical cancer and is now being studied to determine if it can be used in treating earlier stage cervical cancers.²³

More effective testing methods to improve early detection of abnormal cells in the cervix are also being developed. Earlier this year, the U.S. Food and Drug Administration approved the first HPV DNA test. Unlike the Pap smear, which involves visually inspecting sample cells microscopically to find abnormalities, the HPV DNA test scans a sample looking for the unique DNA signature of HPV. A positive response indicates the patient has one of the HPV strains linked with cervical cancer, allowing her physician to conduct a more careful follow-up exam to look for precancerous abnormalities.²⁴