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HIV boosts chances of HPV infection and development of cervical cancer.

Having HIV infection quadrupled chances of getting cervical cancer in an analysis of 38 individual studies. (1) HIV raised chances that a woman would get infected with human papillomavirus (HPV), the virus that causes cervical cancer, anal cancer, and other cancers in women and men. Women with a lower viral load * or taking antiretroviral therapy had a lower chance of acquiring HPV.

Previous research linked HIV infection to a higher rate of HPV infection, a lower rate of clearing HPV from the body, and a higher risk of cervical cancer. (2,3) Cervical cancer is an AIDS cancer and the fourth most common cancer in women across the world.

HPV affects 80% of adult women and 65% to 70% of adult men; it usually passes from one person to another during sex. Researchers have identified over 100 types of HPV. Thirteen of these HPV types are considered high risk because they may cause cancer. Although most HPV infections clear on their own and cause no illness, some infections can persist. Persistent infection with a high-risk HPV type could progress to precancer cell changes and to cancer.

As women with HIV live longer because of antiretroviral therapy, there is a growing need to prevent cervical cancer and to detect precancer cervical changes early. In women living in richer countries, regular Pap testing and the HPV vaccine have proved highly effective in cutting rates of HPV infection and cervical cancer. (4,5)

US researchers conducted this study to combine data from individual studies of HPV and cervical cancer in women with and without HIV. Combining data in this way can give a clearer picture of disease trends. The primary aim was to assess the impact of HIV infection on HPV acquisition, persistence, and progression to precancer cervical changes and to cervical cancer.

How the study worked. The investigators searched electronic medical databases to find studies that examined the impact of HIV infection, CD4 count, viral load, and antiretroviral therapy on (1) acquisition, persistence, or clearance of HPV, (2) progression from HPV infection to low-grade precancer cervical changes, (3) progression from less dangerous cervical cell changes to high-grade precancer changes, (4) regression from low-grade or high-grade precancer changes, or (5) progression from precancer changes to cervical cancer.

The researchers used a standard statistical method to combine data on the impact of HIV on the 5 outcomes listed in the previous paragraph. When possible, they also looked at the impact of CD4 count, viral load, or antiretroviral therapy on these outcomes. Combining data in this way can yield stronger, more meaningful results.

What the study found. Of the 38 studies selected for analysis, 18 took place in North America, 13 in Africa, 6 in Europe, and 1 in Asia.

Twelve studies explored the impact of HIV infection on becoming infected with HPV. Combined results of these studies indicated that having HIV more than doubled the risk of acquiring (1) any HPV type, (2) a high-risk HPV type, or (3) HPV type 16 or HPV type 18. High-risk HPV types are those most likely to cause cancer. Of the high-risk types, HPV types 16 and 18 are notable because they cause about half of all cervical cancers.

Four studies examined the impact of CD4 count on getting HPV infection. Overall, these studies found that the risk of HPV infection increased as CD4 counts decreased. One study found that HPV infection risk fell 18% with every 100-cell higher CD4 count.

Two studies assessed the role of HIV viral load on getting HPV infection. Compared with HIV-negative women, HIV-positive women with a viral load above 10,000 copies had a 3.3 times higher risk of getting HPV infection. HIV-positive women with a viral load below 10,000 copies had a 2.3 times higher risk of HPV.

Eleven studies looked at the impact of HIV on clearance of new or existing HPV infection. Combined results indicated that, compared with HIV-negative women, those with HIV had a 41% to 46% lower chance of clearing any HPV type and a 36% to 44% lower chance of clearing high-risk HPV.

Eight studies explored the impact of HIV on progression from normal cervical cells to low-grade precancer changes. Combined results indicated that women with HIV had a 3.7 times higher risk of progression than HIV-negative women. Risk of low-grade precancer changes was more than 30% lower in women taking antiretroviral therapy (Figure 1). Risk of these low-grade changes fell as CD4 counts rose after antiretroviral therapy began.

Seven studies examined the impact of HIV infection on risk of high-grade precancer cervical changes. Combined results indicated that women with HIV had a 32% higher risk of high-grade precancer changes than HIV-negative women. Risk of progression from HPV infection and normal cervical cells to high-grade cervical changes was 3 times higher in women with HIV than without HIV. Risk of progression to high-grade cervical changes was 34% lower in women who began antiretroviral therapy before detection of low-grade cervical changes and 36% lower in women taking antiretrovirals for 2 years or more.

Combined results of 3 studies determined that women with HIV had a 33% lower chance of regression from low-grade cervical changes to normal cervical cells when compared with HIV-negative women. Taking antiretrovirals and taking antiretrovirals longer raised chances of regression from low-grade cervical changes to normal cervical cells. One study found that HIV-positive women were 43% less likely than HIV-negative women to have regression from high-grade cervical changes to normal cervical cells.

Two studies explored the impact of HIV on development of cervical cancer. A large North American analysis determined that new cervical cancer was 4.1 times more likely in women with HIV than in the general population. A smaller analysis of this same HIV group found that cervical cancer risk rose as CD4 counts fell.

What the findings mean for you. This thorough analysis of 38 previous studies strongly confirms that HIV raises the risk of cervical cancer. (1) These 38 studies consistently found that HIV infection in women boosts the risk of infection with HPV (a cancer-causing virus), development of precancer changes in cervical cells, and ultimately development of cervical cancer. This new multistudy analysis is valuable because (1) it combines results of similar previous studies and thus provides strong conclusions, and (2) it clearly analyzes many details of precancer cervical changes in women with HIV, including the impact of antiretroviral therapy, CD4 count, and HIV viral load.

Two consistent overall findings emerged from this analysis:

* HIV infection strongly raises the risk of HPV infection, precancer cervical cell changes, and cervical cancer.

* Taking antiretroviral therapy, reaching an undetectable viral load, and raising the CD4 count protect against development or progression of cervical changes that can lead to cervical cancer.

Women with HIV can do 3 things to protect themselves from cervical cancer:

1. Take antiretrovirals exactly as your provider instructs to lower your viral load and boost your CD4 count.

2. If you do not already have HPV infection, get the HPV vaccine (Table 1). (6)

3. Talk to your provider about how often you should get a Pap test for cervical changes that can lead to cancer.

Women with HIV should begin getting the Pap test within 1 year of starting sex and no later than age 21.7 They should repeat the test every year. If the first 3 tests are normal, testing can continue every 3 years. Women with HIV should keep getting the Pap test throughout life; they should not stop at age 65. Notes following reference 7 below give providers details on the timing of Pap testing in women with HIV.


(1.) Liu G, Sharma M, Tan B, Barnabas R. HIV-positive women have higher risk of HPV infection, precancerous lesions, and cervical cancer: a systematic review and meta-analysis. AIDS. 2018;32:795-808.

(2.) Clifford GM, Franceschi S, Keiser O, et al. Immunodeficiency and the risk of cervical intraepithelial neoplasia 2/3 and cervical cancer: a nested case-control study in the Swiss HIV Cohort Study. Int J Cancer. 2016;138:1732-1740.

(3.) Strickler HD, Burk RD, Fazzari M, et al. Natural history and possible reactivation of human papillomavirus in human immunodeficiency virus-positive women. J Natl Cancer Inst. 2005;97:577-586.

(4.) Hariri S, Bennett NM, Niccolai LM, et al. Reduction in HPV 16/18-associated high grade cervical lesions following HPV vaccine introduction in the United States--2008-2012. Vaccine. 2015;33:1608-1613.

(5.) Vaccarella S, Lortet-Tieulent J, Plummer M, Franceschi S, Bray F. Worldwide trends in cervical cancer incidence: impact of screening against changes in disease risk factors. Eur J Cancer. 2013;49:3262-3273.

(6.) Centers for Disease Control and Prevention (CDC). Human papillomavirus (HPV). HPV vaccines: vaccinating your preteen or teen.

(7.) Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. May 29, 2018.

For women younger than 30:

"The Pap test is the primary mode for cervical cancer screening for women with HIV aged <30 years. Screening for these women should commence within 1 year of the onset of sexual activity regardless of mode of HIV transmission (e.g., sexual activity, perinatal exposure) but no later than 21 years old. Women with HIV aged 21 to 29 years should have a Pap test at the time of initial diagnosis with HIV. Provided the initial Pap test for a young (or newly diagnosed) woman with HIV is normal, the next Pap test should be in 12 months. Some experts recommend a Pap test at 6 months after the baseline test. If the results of the 3 consecutive Pap tests are normal, follow up Pap tests should be every 3 years. Co-testing (Pap test and HPV test) is not recommended for women with HIV <30 years of age."

For women 30 or older:

"If screening with Pap tests alone, a woman with HIV should have a Pap test at the time of HIV-diagnosis (baseline), then every 12 months. Some experts recommend a Pap test at 6 months after the baseline test. If the results of the 3 consecutive Pap tests are normal, follow-up Pap tests should be every 3 years."

* Words in boldface are explained in the Technical Word List at the end of this issue.
Table 1. Who should get the HPV vaccine when?

* Girls and boys 11 or 12 years old

(2 vaccine shots 6 to 12 months apart)

* Adolescents who have not already had the vaccine
(3 shots over 6 months if child is older than 14)

* Everyone with HIV from 9 to 26 years old
(3 vaccine shots)

* Young men who have sex with men through age 26

* Young adults who are transgender through age 26

Source: Centers for Disease Control and Prevention (CDC). (6)

Figure 1. Combined analysis of several studies indicated that
Antiretroviral therapy (ART) has numerous benefits in slowing
or reversing precancer cervical cell changes that can
develop into cervical cancer.

Antiretroviral therapy (ART) impact
on precancer cervical cell changes

Risk of low-grade     Risk of progression to   Regression from low-
Precancer changes     high-grade precancer     grade precancer
                      changes                  changes

* Over 30% lower      * 34% lower when         * Higher chance with
with ART              AAT starts before        ART
                      low-grade changes

* Falls as CD4 count  * 36% l ower with ART    * Higher chance with
rises with WRT        for 2 years or more      longer ART
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Title Annotation:ARTICLE 3; human papillomavirus
Publication:HIV Treatment: ALERTS!
Date:Dec 1, 2018
Previous Article:Half of women with HIV and GYN cancer do not receive standard cancer therapy.
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