HIV-positive women often infected with multiple HPV subtypes

A study published in the November 28^th edition of AIDS has shown that HIV-positive women are more likely to carry multiple strains of human papilloma virus (HPV) - the virus that can lead to cervical cancer.

Human papilloma virus (HPV) is a family of viruses that can infect the cervix, vagina, and rectum. There are dozens of different subtypes of HPV: some result in genital and anal warts, some have very little effect, and others can cause infected cells to become abnormal. These abnormalities may then worsen, eventually leading to cervical (or anal) cancer if undetected or untreated.

What is known about HPV and cervical cancer in HIV-positive women?

Compared to HIV-negative women, HIV-positive women are more likely:

 

• to be infected with HPV,
• to have longer-lasting HPV infections,
• to have a greater number of different types of HPV at the same time, and
• to develop cervical cancer as a result of the infection.

 

Out of the different subtypes of HPV, some are more likely than others to cause cancer. HPV subtypes 16, 18, 31, 33 (especially 16) are the most likely to lead to cancer, in both HIV-positive and negative women. However, given the large number of different subtypes of virus, the question has remained: does being infected with a greater number of different HPV subtypes mean a greater risk of cellular abnormalities and cancer? This question was investigated by researchers in the current study.

Investigating infection with more than one HPV subtype

The HPV and HIV Study Group is a collective of researchers from around the world. In this study, three group members from France and Brazil conducted a “meta-analysis” of existing data. In other words, they pooled data already gathered from 5,578 HIV-positive women in 20 smaller studies, and conducted a large-scale analysis. The pooled data included women from Africa, Asia, Europe, South and Central America, although nearly 60% were North American. The data were also compared to published information from previous studies in HIV-negative women. The research team looked at the following questions:

 

• How common were the various HPV subtypes?
• How many different types of HPV was any one woman likely to be infected with?
• How common was HPV16 – the type most likely to lead to cancer?

 

The team studied the differences between women with three different levels of cervical cell abnormalities:

 

• Normal (i.e. no cellular abnormalities).
• Low-grade (technically, “atypical squamous cells of undetermined significance” – ASCUS – or “low-grade squamous intraepithelial lesions” – LSIL).
• High-grade (“high-grade squamous intraepithelial lesions” – HSIL).

 

How common was HPV in HIV-positive women?

The study found that over one-third of all HIV-positive women without cellular abnormalities (36.3%) were infected with HPV. As would be expected, HPV infection was more likely in women with more advanced cervical cell abnormalities.

HIV-positive women were more likely to be infected with a number of different HPV types than HIV-negative women. In the group of women with HSIL, HPV was equally common in HIV-positive and HIV-negative women. However, many more of the HIV-positive women (41.1%, compared to only 6.7%) had more than one type of HPV. Findings were as follows:

 

In HIV-positive women with…	% with HPV (any type)	% with multiple types of HPV
Normal cells (no abnormalities) – 3230 women:	36.3%	11.9%
Low-grade abnormalities (ASCUS/LSIL) – 2053 women:	69.4%	34.7%
High-grade abnormalities (HSIL) – 295 women:	84.1%	41.4%
In the “general population”* with HSIL – 4338 women	84.2%	6.7%

(*“General population” refers to studies of women overall, with no distinction as to HIV status.)

Regional differences

HPV was found in 57.3% of “cytologically normal” HIV-positive women in South and Central America, 56.6% in Africa, 32.4% in Europe, 31.4% in North America, and 31.1% in Asia. Different subtypes also varied between regions.

How common was HPV16?

HPV16 - the subtype most likely to lead to cervical cancer – was the most common HPV subtype, found in 12.4% of all women with HPV. It was more widespread among women with higher-grade cell abnormalities.

However, among the women with the worst lesions (HSIL), HPV16 was actually less common in HIV-positive women (31.9%, compared to 45% in the general population). HIV-positive women were more likely to be infected with “high-risk” subtypes other than HPV16 (i.e., HPV18, 51, 52 and 58), or with subtypes classified as “low-risk” for cancer. The researchers speculated that “these types, which have little potential to cause [cancerous] changes in women without an HIV infection, may induce HSIL in immunosuppressed women.”

Study conclusions and questions raised

This meta-analysis presents a large amount of complex data on different types of human papilloma virus and their effects on HIV-positive women. The bottom line is that HIV-positive women with serious abnormalities in their cervical cells are less likely to have HPV16 – the cause of half of all cervical cancer worldwide – and more likely to have other, or multiple different, types of HPV.

Issues raised regarding HPV vaccines

Vaccines have recently become available to protect against the four highest-risk types of HPV (types 16, 18, 6, and 11). But there is currently little information on how safe and effective these vaccines are in HIV-positive women. As stated in an editorial accompanying the study, these “vaccines are reported to be about 95% effective against primary infection with the targeted high-risk HPV types that together account for about 70% of cervical cancers.” However, “the wide diversity of HPV types among HIV-positive women … raises important questions about how prophylactic vaccines should be used to reduce cervical cancer risk in HIV-positive women.”

Compulsory vaccination?

Meanwhile, the possibility of compulsory HPV vaccination is being considered – an issue explored in an editorial in the December 6^th edition of the New England Journal of Medicine. Given that more than six million people in the US become infected with HPV every year, and nearly 10,000 women are diagnosed with cervical cancer, the vaccine has great potential to avert serious illness and death. Since the vaccine “has the greatest benefit when it is given before a person becomes sexually active”, the Centers for Disease Control have recommended that it be routinely given to girls at age 11 or 12. The state of Michigan is already considering a bill to make HPV vaccination compulsory for girls entering sixth grade (with an opt-out option for parents who object); other states are likely to follow.

Given that HPV is sexually transmitted, this proposal has, unsurprisingly, sparked debate. On the “pro” side, public health advocates argue that mandatory vaccinations protect the largest number of people – not only those who are actually vaccinated, but those they come into sexual contact with. On the other side, as James Colgrove states in his editorial, “opposition to [such] mandates will come from a far wider range of constituencies than just religious conservatives worried about threats to teenagers’ sexual abstinence.” In the past two decades, as the number of recommended (and enforced) vaccines has grown, so have objections from those who hold “the values of patient autonomy and informed consent to be preeminent”.

While “[requiring] HPV vaccination by law will almost certainly achieve more widespread protection against the disease than [relying] exclusively on persuasion and education”, a “critical question is whether … a higher level of coverage justifies the infringement on … autonomy that compulsory vaccination inevitably entails.”