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Anal Cancer and HIV

Kaposi's sarcoma (KS), and non- Hodgkin lymphoma (NHL) were common AIDS associated malignancies before potent antiviral therapy became available.   The incidence of these two malignancies used to be 50-200 times higher among HIV positive individuals  than in those who were HIV uninfected.  These two malignancies are caused by herpes viruses, HHV8 in the case of KS and EBV in the case of NHL.

Cervical cancer and anal cancer also occur more frequently in association with HIV infection. These two cancers, like KS and NHL are also caused by viruses. These viruses are members of the human papillomavirus family (HPV), types 16 and 18 being the most frequent.  Over 90% of anal cancers are associated with HPV type 16.    HPV viruses are more usually the cause of common warts.  

Potent anti-HIV therapy has reduced the incidence of KS and NHL by 80-85%.  Unfortunately treatment has not had the same effect on HPV associated cancers.   Some studies show an increasing trend in the incidence of cervical and anal cancers, an effect most likely due to increased survival.

I was prompted to write this entry after reading an important report about HIV and anal cancer which has just appeared in an advance access edition of the Journal,  Clinical Infectious Diseases.  The lead author is Alexandra de Pokomandy.

Its title is:  HAART and progression to high grade anal intraepithelial neoplasia in men who have sex with men and are infected with HIV.

Many of the article's conclusions have been reported before, but this one is important because it has the power of a prospective study.   A prospective study is one in which participants are examined at regular intervals after entering the study and checked for the development of any changes over time.  Most previous studies on the association of anal cancer and HIV infection were not prospective studies.

In this study 247 HIV positive MSM were followed every  6 months for 3 years.  They were tested by examining anal smears for high grade anal intraepithelial neoplasia (AIN).  AIN is a local condition in the anus  that can progress to invasive cancer, higher grades of AIN being more likely to do so.

 The number studied is not huge, but we cannot ignore the findings.


Firstly, in line with previous studies (most were not prospective), treatment with HAART did not reduce the incidence of AIN.   There was a hint that treatment lasting over four years might have an effect. .

The study attempted to define what the risk factors were for developing AIN among men who entered the study,


Firstly this is the cumulative rate at which AIN increased during the study.


anal cancer.jpg

The illustration shows the increasing proportion of men with more advanced forms of AIN  (AIN2 and AIN3) over time.     The increase is shown for three groups of men. Those very very few who were HPV negative at baseline (lower line), those with high risk HPV type 16 at baseline (top line), and in the middle line those with HPV types other than type 16 at baseline.

Just looking at the top line, under 50 % of those who had HPV type 16 at baseline already had AIN 2/3 at the start of the study.  By 36 months the proportion with AIN 2/3 had risen to about 75%.



The authors attempted to define what the risks for developing AIN 2/3 were.  As noted, antiviral treatment made no difference. 

What was significant in increasing the risk of progression to AIN2/3 was the CD4 nadir, and the number of different HPV types isolated.


A word about anal intraepithelial neoplasia - AIN:

AIN is not invasive anal cancer.   The development of aggressive anal cancer occurs in stages that can be identified by examining cells obtained by PAP smears.   Progression from one stage to the next is not inevitable.

For example, in the above study 39% of HIV positive men developed AIN 2/3 over 3 years.  But extrapolating from other data only 0.12 % of men would be expected to develop aggressive anal cancer over the same period, according to an editorial accompanying the report.

The editorial concludes as follows:

 "These results show that HAART has not reduced the prevalence of HPV infection, has not changed the natural history of anal HPV infection in HIV-positive MSM, and has not mitigated the progression to high-grade AIN (which is likely to be a precursor to anal cancer, in much the same way that cervical dysplasia is the precursor to cervical cancer").

This is not good news but it does give us a very clear basis on which to act.

 We know what has to be fixed, and the study has provided us with a few suggestions.

These are some that jumped at me:

  1.  The risk for developing aggressive anal cancer is related to the CD4 nadir. This is yet an additional and powerful reason to be tested for HIV and make sure the CD4 count does not fall further.
  2. Screening of women for cervical dysplasia with regular PAP smears has had an effect in preventing cervical cancer. There are several treatment options.  It's  important that MSM be screened with regular anal  PAP smears.       It's important that health care providers know how to do this and that the PAP smears are competently examined.  It goes without saying that every effort needs to be made to insure that   problems with reimbursement for the procedures are not an obstacle. 
  3.  Very unfortunately treatment of AIN is not as simple as dealing with cervical lesions.     This means that efforts to improve the management of AIN must be studied and that funds be made available for this.
  4. Another risk for the development of AIN 2/3 that was identified was the number of different HPV types present.   Although there is no clear evidence on the role of condoms in preventing anal HPV infection it seems absolutely reasonable to accept that there are circumstances when receptive partners in anal intercourse would be safer to insist that their partner use a condom.      The more HPV types there are the greater the risk for more advanced forms of AIN and therefore aggressive anal cancer.
  5. HPV vaccines.    These obviously work best if given before the onset of sexual activity so the vaccination of boys and young men is a good idea.  For older individuals it's possible that some have not yet acquired HPV 16 or 18.   Apart from cost, there appears to be no harm.      Studies on therapeutic HPV vaccines should be supported.
  6. Although this study was done in men we should consider the implications for women.  In the general population anal cancer is rare, but more cases have been reported in women than in men, and HIV infection increases the risk in both.  New York State health department  guidelines recommend annual anal PAP smears for HIV positive women with abnormal cervical smears.  These are 2007 guidelines; there may be updates that I have not seen.  Even if it remains unclear if anal intercourse adds to the risk of anal cancer in women, this seems likely  and so we should work out ways to offer regular screening to women who might be at greater risk.


So many aspects of HIV infection can be ameliorated by antiviral treatment, but sadly not everything.  Cancers of the cervix and anus are among these.  But there are measures that we can take to lessen risk, some mentioned above. 

Readers of my blog will know that I think that the promotion of daily Truvada to prevent HIV infection is unwise. I find it incomprehensible that the CDC has issued an interim guidance on its use. It does not even halve the chance of acquiring a life threatening infection, one for which treatments cannot prevent the increased risk for cervical and anal cancer.  Condoms are much more effective, they are cheaper, safer and readily available, and we should not be distracted from promoting and facilitating their use, and continuing to provide   support for their use with an alternative that just does not work well enough.

Sean on:


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Comments on Joseph Sonnabend, MD's blog entry "Anal Cancer and HIV"

Dr. Sonneband

Just read your article in PIOZ and I thought to take this time to lt you know that you are in my thoughts constantly. You gave hope and help to those with AIDS - you especially took great care of my brother Jim.

I will never forget you.

Giorgia, I too can't forget. This also brings back CRI, Tom, and all we did on 26th street more than 20 years ago!

My doc does the scope thing to check for recurrence of warts and to visually look for cancers, but says pap smear is a waste of time since there is no treatment guideline regardless of the result.

Regular anoscopy to detect warts and treat them is part of good medical care. But detecting precancerous changes requires that cells be examined microscopically. Pap tests are the simplest way to obtain material to examine.

There may be no treatment guidelines regarding the best way to deal with different grades of precancerous changes but that does not mean that there are no ways to manage such abnormalities. Unfortunately, as I mentioned treatment is much less effective than that of cervical dysplasia, with high rates of recurrence and difficulties following procedures. Non surgical approaches may be effective in some situations such as infrared coagulation or applying imiquimod.

Also optimal screening methods and schedules are yet to be established.
Just this month a pilot anal pap screening project was described. You can take a look here:

This is in it:

"There is a possibility that HIV health care providers may be deterred
from instituting any form of anal cancer screening for HIV-
infected individuals by the perception that screening is time-
and resource-consuming. The same could be said regarding
the absence of reports of the benefits of such screening. A
study such ours demonstrates the feasibility of anal Pap smear
screening in routine HIV care that makes possible the early
detection of precancerous and even cancerous lesions".

If ever a research objective needed urgent prioritizing and all the support we can give to it is this: To improve the management of anal precancerous and local cancerous lesions that includes optimal screening procedures and treatment options.

I'll end with a quote from the above article.

"Until there is a consensus regarding anal Pap smear screening, HIV-infected
patients need to know they are at risk of anal cancer, and anal
health should be an issue of priority for HIV care providers to
discuss with their HIV-positive patient".

Thanks for this information. I have an appt. with my colon/rectal doc for my annual checkup tomorrow. I will re-visit the issue with him. I read the referenced report and will bring it along. There still seems to be a lack of a clear action plan for a high grade diagnosis, but perhaps some options are out there, such as the imiquimod.

I don't understand why HPV innoculation isn't being suggested/recommended for those of us who are at risk for anal infection. What's with that???

Current HPV vaccines prevent infection so are of no use in individuals already infected.

So it's a good idea to vaccinate boys and younger men before the onset of sexual activity.

Still, you ask a very good question. In the study I commented on, 38.2% of the men had HPV- 16 at baseline, and 24.5% had HPV- 18. So, the majority of men were free from these high risk types when entering the study. Of course one cannot extrapolate from this group of 247 men, recruited in Montreal. (Their median age was 43, with a median CD4 count of 380).

It's reasonable to accept that at any particular time, there's a realistic chance that a significant number of men at risk will be free from high risk HPVs, particularly types 16 and 18, the likelihood decreasing with increasing age and experience.

I don't know if there are any prospective studies of HPV vaccination in HIV positive MSM who are free from the high risk HPVs present in the vaccines.

I'm unaware of any significant harmful effects of the vaccine, and for the moment, until we have study results, HPV vaccination seems to be a very reasonable option for those able to afford it. It may be too late to be of use because infection with high risk HPVs may have already occurred, but it causes no harm and may benefit some. Of course we cannot know if this is so until prospective studies are completed.

But even without testing for specific HPV types, a choice to recieve an HPV vaccine seems reasonable. Even though we cannot know it will be of benefit (only studies can determine this), there seems to be no down side - of course apart from cost.

Considering the gravity of a diagnosis of anal cancer, for those at risk, HPV vaccination seems to be a perfectly reasonable option even in the absence of proof that it will be of benefit. It causes no harm - apart from cost, and may be of benefit to some.


For more information on MSM and HPVs and the charcteristics of men in Montreal participating in the prospective study take a look at this article:

"Prevalence, Clearance, and Incidence of Anal
Human Papillomavirus Infection in HIV-Infected
Men: The HIPVIRG Cohort Study"

Added March 25:

A study has in fact been completed on the effects of HPV vaccination in preventing AIN – the precancerous changes in the anus described in my blog entry. Gardasil was effective in preventing AIN associated with high risk HPVs in men younger than 26 who had not been infected with the vaccine HPV types. The FDA approved Gardasil for the prevention of anal cancer in individuals aged between 9 and 26.

But as I noted, there is a good chance that significant numbers of men at risk who are older than 26 will be free of some HPV types 16, 18, 6 and 11. So even without testing for specific HPV types, vaccination of older men at risk may well have a protective effect in some. Of course there will be no benefit in those already infected with all four of the HPVs in the vaccine, but apart from cost there is no down side.

Dear Sirs: Thanks so much for the information, I am a 29+ year survivor of HIV/AIDS, at 58 I recently had a routine colonoscopy, and was diagnosed with AIN2....I had no idea there was a problem. Now I'm confronted with making a decision about what form of treatment to undertake. My gastroentorologist has referred me to a surgeon, who want to scrape away three of the four layers where these are located...and then I have other professionals in the HIV field who say that infrared oblation is the way to go...I'm confused, and not sure which route to take...anyone have any suggestions.

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This page contains a single entry by Joseph Sonnabend published on March 5, 2011 9:08 AM.

Remembering the Original AZT Trial was the previous entry in this blog.

Interferon and AIDS: Too much of a good thing is the next entry in this blog.

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