The Facts About HIV and Cervical Cancer

Despite Advances, the Incidence Among Women with HIV Remains Unchanged

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People with HIV have an elevated risk of developing certain cancers, a number of which can be classified as AIDS defining conditions. Among them is invasive cervical cancer (ICC), a stage of disease by which cancer spreads beyond the surface of the cervix to deeper tissues of the cervix and other parts of the body.

While ICC can develop in both HIV-infected and non-infected women, the incidence among women with HIV can be as high as seven times greater.

In women with HIV, the ICC risk is seen to increase with decreases in the CD4 count, with a nearly six-fold increase in women with CD4 counts under 200 cells/mL compared to those with CD4 counts over 500 cells/mL.

About Cervical Cancer

Human papillomavirus (HPV) is considered integral to developing cervical cancer, accounting for nearly all documented cases. As with all papillomaviruses, HPV establishes infections in certain cells of the skin and mucosal membranes, most of which are harmless.

Around 40 types of HPV known to be sexually transmitted and can cause infections around the anus and genitals, occasionally appearing as warts. Of these, 15 "high-risk" types can lead to developing precancerous lesions. If left untreated, the precancerous lesions can sometimes progress to cervical cancer. Disease progression is often slow, taking years before visible symptoms develop. However, in those with compromised immune systems (CD4 less than 200 cells/ml), the progression can be far more rapid.


Early detection by way of regular Pap smear screening has dramatically decreased the incidence of cervical cancer in recent years, while the development of HPV vaccines has led to further reductions by preventing the high-risk types associated with 75% of cervical cancers.

The estimated HPV prevalence among women in the U.S.

is 26.8%., while 3.4% are infected with high-risk HPV types 16 and 18, which account for around 65% of cervical cancers.

Cervical Cancer in Women with HIV

Despite these advances, cervical cancer is still considered the second most common cancer among women worldwide, accounting for approximately 225,000 deaths annually. While the majority of cases are seen in the developing world (due to the paucity of Pap screening and HPV immunization), cervical cancer still accounts for nearly 4,000 deaths in the U.S. each year.

More concerning yet is the fact that the incidence of cervical cancer among HIV-infected women has remained unchanged since introducing antiretroviral therapy (ART) in the late 1990s. This is in stark contrast to Kaposi's sarcoma and non-Hodgkin lymphoma, both AIDS-defining conditions which have dropped by over 50% during the same period.

While the reasons for this are not fully understood, a small but relevant study by the Fox Chase Cancer Center in Philadelphia suggests that women with HIV may not benefit from the HPV vaccines commonly used to prevent the two predominant strains of the virus (types 16 and 18).

Among women with HIV, types 52 and 58 were most frequently seen, both of which are considered high-risk and impervious to the current vaccine options.

Symptoms of Cervical Cancer

There are often very few symptoms in the early stages of cervical cancer. In fact, by the time vaginal bleeding and/or contact bleeding occurs—two of the most commonly noted symptoms—a malignancy may have already developed. On occasion, there may be a vaginal mass, as well as vaginal discharge, pelvic pain, lower abdominal pain, and pain during sexual intercourse.

In advanced stages of disease, heavy vaginal bleeding, weight loss, pelvic pain, fatigue, loss of appetite, and bone fractures are the most frequently noted symptoms.

Diagnosis of Cervical Cancer

While Pap smear tests are recommended for screening purposes, false negative rates can be as high as 50%. Confirmation of either cervical cancer or cervical dysplasia (the abnormal development of cells the cervical lining) requires a biopsy for examination by a pathologist.

If cervical dysplasia is confirmed, it is classified based on the degree of severity. Pap smear classifications can range from ASCUS (atypical squamous cells of uncertain significance) to LSIL (low-grade squamous intraepithelial lesion) to HSIL (high-grade squamous intraepithelial lesion). Biopsied cells or tissue is similarly graded as either mild, moderate or severe.

If there is a confirmed malignancy, it is classified by the stage of disease based on the clinical examination of the patient, ranging from Stage 0 to Stage IV as follows:

  • Stage 0: A carcinoma in situ (a localized malignancy that has not spread)
  • Stage I: Cervical cancer that has grown in the cervix, but has not spread beyond it
  • Stage II: Cervical cancer that has spread, but not beyond the walls of the pelvis or the lower third of the vagina
  • Stage III: Cervical cancer that has spread beyond the pelvis walls or lower third of the vagina, or has caused hydronephrosis (accumulation of urine in the kidney due to an obstruction of the ureter) or the non-functioning of the kidney
  • Stage IV: Cervical cancer that has spread beyond the pelvis to adjacent or distant organs, or has involved mucosal tissue of the bladder or rectum

Treatment of Cervical Cancer

The treatment of pre-cancer or cervical cancer is determined in large part by the grading or staging of the disease. Most women with mild (low-grade) dysplasia will undergo spontaneous regression of the condition without treatment, requiring only regular monitoring.

For those in whom dysplasia is progressing, treatment may be required. This might take the form of an ablation (destruction) of cells by electrocautery, laser, or cryotherapy (freezing of cells); or by resection (removal) of cells through electrosurgical excision (also known as long electrical excision procedure, or LEEP) or conization (the conical biopsy of tissue).  

The treatment of cervical cancer can vary although greater emphasis is being placed on fertility-sparing therapies. Treatment can take the form of one or several of the following, based on severity of the disease:

  • Chemotherapy
  • Radiation therapy
  • Surgical procedures, including LEEP, conization, hysterectomy (removal of the uterus), or trachelectomy (removal of the cervix while preserving the uterus and ovaries).

Generally speaking, 35% of women with cervical cancer will have a recurrence after treatment.

In terms of mortality, survival rates are based on the stage of disease at the time of diagnosis. Generally speaking, women diagnosed at Stage 0 having 93% chance of survival, while women at Stage IV have 16% survival rate.

Prevention of Cervical Cancer

Traditional safer sex practices, Pap smear screening, and HPV vaccination are considered the three leading methods of cervical cancer prevention. Furthermore, the timely initiation of ART is considered key to reducing ICC risk in women with HIV.

The U.S. Preventive Services Task Forces (USPSTF) currently recommends Pap screening every three years for women between the ages of 21 and 65, or alternatively every five years for women ages 30 to 65 in conjunction with HPV testing.

Meanwhile, HPV vaccination is currently recommended for any girl or young woman who has had sexual contact. The Advisory Committee on Immunization Practices (ACIP) suggest routine vaccination for girls 11 to 12 years of age, as well as women up to the age of 26 who have not had or completed a vaccination series.

Two vaccines are currently approved for use: a quadrivalent vaccine which can prevent types 6, 11, 16 and 18 (Gardasil) and bivalent vaccines that can protect against types 16 and 18 (Cervarix). Each requires a series of three shots given over a six-month period.

While the vaccines can't protect against all HPV types, researchers at the Fox Chase Cancer Center confirm that HIV-positive women on ART are far less likely to have high-risk HPV types 52 and 58 than their untreated counterparts. This reinforces the argument that early ART is key to preventing both HIV-related and non-HIV-related cancers in people with HIV.

Future Therapies and Strategies

In terms of developing strategies, recent studies have suggested that the commonly prescribed antiretroviral drug, lopinavir (found in the fixed dose combination drug Kaletra), may be able to prevent or even reverse high-grade cervical dysplasia. Early results showed a high rate of efficacy when delivered intravaginally in twice-daily doses over three months.

If the results can be confirmed, women may one day be able to treat cervical pre-cancer at home, while those with HIV may be able to prophylactically prevent HPV as part of their standard ART.


Abraham, A.; D’Souza, G.; Jing, Y.; et al. "Invasive cervical cancer risk among HIV-infected women: a North American multicohort collaboration." Journal of Acquired Immune Deficiency Syndromes. April 1, 2013;  62(4):405-413.

Adler, D. "The impact of HAART on HPV-related cervical disease." Current HIV Research. October 8, 2010; 8(7):493-7.

Dunne, E.; Unger, E.; MD; Sternberg, M.; et al. "Prevalence of HPV Among Females in the U.S." Journal of the American Medical Association. February 28, 2007; 297(8):813-819.

Dames, D.; Blackman, E.; Butler, R.; et al. "High-Risk Cervical Human Papillomavirus Infections among Human Immunodeficiency Virus-Positive Women in the Bahamas." PLoS | One. January 23, 2014; 9(1): e85429. doi: 10.1371.

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U.S. Preventive Services Task Force (USPSTF). "U.S. Preventive Services Task Force Issues New Cervical Cancer Screening Recommendations: Evidence shows that cancer screening is effective." Rockville, Maryland; issued March 15, 2013.

Centers for Disease Control and Prevention (CDC). "Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Council on Immunization Practices (ACIP)." Morbidity and Mortality Weekly Review (MMWR). March 23, 2007; 56(RR02).1-24.

Centers for Disease Control and Prevention (CDC). "FDA Licensure of Bivalent Human Papillomavirus Vaccine (HPV2, Cervarix) for Use in Females and Updated HPV Vaccination Recommendations from the Advisory Committee on Immunization Practices (ACIP)." Morbidity and Mortality Weekly Review (MMWR). May 28, 2010; 59(20);626-629.

Hampson, I.; Hampson,L.; Batman, G.; et al. "Lopinavir up-regulates expression of antiviral protein ribonuclease L in human papillomavirus-positive cervical carcinoma cells." Antiviral Therapy. 2011; 16(4):515-525.

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