The Facts About HIV and Cervical Cancer

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.

Woman in medical gown waiting in doctor's office

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

In women with HIV, the ICC risk is correlated 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 a leading cause of 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 are known to be sexually transmitted and can cause infections around the anus and genitals - including genital 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 signs 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 percent of cervical cancers. Guidelines from the U.S. Preventative Services Task Force recommend Pap tests every three years from ages 21 to 29, then co-testing of Pap test and HPV primary test from 30 to 65 every five years, or only a Pap test every three years. The other options is testing for HPV alone every five years.

The estimated HPV prevalence among women in the U.S. is 26.8 percent, and of that number 3.4 percent are infected with high-risk HPV types 16 and 18. Types 16 and 18 account for around 65% of cervical cancers.

Cervical Cancer in Women with HIV

Cervical cancer is the second most common cancer among women worldwide, accounting for approximately 225,000 deaths globally every year. 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 percent 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 the 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

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 loop electricosurgical excision procedure, or LEEP) or conization (the conical biopsy of tissue).  

The treatment of cervical cancer can vary although the greater emphasis is being placed on fertility-sparing therapies. Treatment can take the form of one or several of the following, based on the 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 have a 93% chance of survival, while women at Stage IV have a 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 American Cancer Society (ACS) updated cervical cancer screening guidelines recommend that people with a cervix undergo HPV primary testing — instead of a Pap test — every five years, starting at age 25 and continuing through 65. More frequent Pap tests (every three years) are still considered acceptable tests for offices without access to HPV primary testing. The previous ACS guidelines, released in 2012, advised screening to begin at age 21.

The Advisory Committee on Immunization Practices (ACIP) suggests routine vaccination for boys and girls 11 to 12 years of age, as well as men and women up to the age of 26 who have not had or completed a vaccination series.

Two vaccines are currently approved for use: Gardasil9 and Cervarix. Gardasil 9 is only approved option currently available in the US and is indicated for people ages 9 through 45.

While Pap smear tests are recommended for screening purposes, confirmation of either cervical cancer or cervical dysplasia (the abnormal development of cells the cervical lining) requires a biopsy for examination by a pathologist.

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 prevent HPV as part of their standard ART.

1 Source
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  1. Fontham ETH, Wolf AMD, Church TR, et al. Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J Clin. 2020;10.3322/caac.21628.

Additional Reading

By James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.