Trial Information

Human Papillomavirus (HPV) Infection in Young Men Who Have Sex With Men

Study aims

The objectives of this study are to determine among younger MSM:

1. The prevalence of HPV infection, distinguishing this from HPV deposition

2. Sexual behaviours associated with varying prevalence of HPV infection

Methods

Eligibility for study Younger, less sexually experienced MSM will be recruited into a study
with 4 visits over 12 months. The study will aim to recruit men who have reported the least
number of prior male sexual partners to maximize the inclusion of men who have not been
previously HPV infected.

Data from the Health in Men (HIM) cohort of Sydney men indicate that for MSM aged less than
25, the mean age of first homosexual contact was approximately 16 years. Men in this age
group reported coming out on average at 17 years while the mean age for first anal sex was
18 years (unpublished data). Furthermore, survey data from Australian MSM attending
community events show that about 20% of teenage MSM under the age of 18 had reported more
than 10 male partners over the prior 6 months (unpublished data). In a community based
study of Australian MSM, the prevalence of any anal HPV infection among those aged 25-34 was
almost 80% among HIV uninfected men and higher among HIV infected men (Vajdic, 2009). These
data suggest the importance of including teenage MSM in the cohort.

Criteria for eligibility:

- Men aged 16 to 20

- Report previous sexual contact (any type of sexual contact) with at least one other man
ever

- Able to complete all study requirements including questionnaire in English and
completion of 4 visits

No restriction will be placed in relation to the number of previous sexual partners;
however, the investigators will aim to recruit men in the younger part of the age range and
review the number of men recruited as the study progresses.

Recruitment

The investigators will use a number of avenues for recruitment recognizing the fact that
this may be a group that is potentially difficult to access for the purposes of study
recruitment. Possible avenues for recruitment:

Facebook, Twitter and other web based social networking sites. Using Facebook the
investigators would be able to target advertising for the study according to age, sexual
preference and state of residence with a link back to the study page. Facebook has been used
effectively for promotion of the PASH study to Australian MSM.

Online groups and forums that target young MSM. These may include:

- Minus 18 - Melbourne based
(http://www.minus18.org.au/index.php?option=com_content&task=view&id=23&Itemid=39)

- Oz Lounge - Australia wide (http://www.ozlounge.com.au/)

- Mogenic - Australia wide (http://www.mogenic.com/)

- Twenty10 - Sydney based (http://www.twenty10.org.au/)

Groups that support young MSM. These could include:

- Support groups for young MSM and those coming out
(http://www.glhv.org.au/files/QueerNet%20brochure.pdf))

- Gay youth services (e.g. Family Planning (Victoriahttp://www.fpv.org.au/3_5_2.html))

- Other groups:
(http://www.switchboard.org.au/OurVictoriancommunity/Victoriandatabase/youth/tabid/104/Default.aspx) and (http://au.reachout.com/find/issues/sexuality-coming-out)

Groups supporting MSM in regional areas e.g:

- Mind the Gap (http://www.glhv.org.au/files/Mind%20The%20Gap%20Overview%202009.pdf)

- Country Awareness Network (http://www.can.org.au/)

Cruising websites such as Gaydar and Manhunt. These are probably less ideal as men are
required to be at least 18 years of age and will likely be more sexually active.

Student unions at universities targeting MSM, e.g. Melbourne University, Royal Melbourne
Institute of Technology (RMIT), etc.

Health promotion offices in different universities.

The investigators will as much as possible avoid labeling the study as one targeting gay men
so that men who do not identify as being gay are not dissuaded from participating.
Recruitment and study visits will take place in Melbourne with the possibility of
recruitment in Sydney depending on how the study progresses.

Study visits and schedule (see Appendix 1) Study visits will be conducted at baseline, 3
months, 6 months and 12 months. Face to face visits will be conducted at all four visits at
the Melbourne Sexual Health Centre.

Questionnaire and website A website will be set up that provides information about the study
and which will allow men to complete questionnaires at each of the four visits online during
the visit. The site will also provide illustrated instructions/video on sampling for HPV(15)
as well as general information about HPV, other STIs, Melbourne Sexual Health Centre (MSHC)
clinical services and the 1800 telephone for the study.

At each study visit men will be asked to complete a detailed questionnaire regarding recent
sexual partners and sexual practices. Men will be sent reminders via email or SMS to attend
study visits. The questionnaire will include questions that measure the extent of prior
specific sexual practices men have engaged in.

Men will also be asked to self report the onset of any oral, genital or anal warts. At the
first visit men will be shown images of anogenital warts and will be asked to attend the
MSHC for confirmation of the diagnosis. The investigators will obtain permission from men to
access their medical records at MSHC and elsewhere so any self reported diagnoses of
anogenital warts can be confirmed.

In addition to the above, the baseline questionnaire will include questions regarding
demographics and other possible co-factors in HPV acquisition and persistence including
circumcision status and smoking.

1. Oral sampling for HPV

The method to be employed for oral sampling in this study will be determined in a
separate study comparing oral rinse with swab.

2. Anal sampling for HPV

Previous studies of HPV in the anus have generally employed moistened swabs collected
from the anal canal. The investigators will use the same technique in this study using
a flocculated swab and saline.

3. Penile sampling for HPV

Studies aimed at detecting male genital HPV infection have used sampling from different
anatomical sites including the glans penis, coronal sulcus, prepuce (in uncircumcised men),
shaft and scrotum. In some studies these have involved sampling after the application of
emery paper designed to remove the superficial layer of the epidermis, exposing the basal
layer where HPV virus is present.

In a preliminary study of 30 men, use of emery paper was shown to improve the detection of
beta-globin from penile samples using saline wetted Dacron swabs while cytobrush was found
to be inadequate. In a further, larger sample of men, using emery paper and saline wetted
Dacron swabs, HPV DNA was detected in 24% of men: 24% from the penile shaft, 16% from the
glans, 28% from the foreskin, 17% from the scrotum, 6% in urine(16). The authors concluded
that testing at multiple genital sites increased the number of men for whom HPV DNA was
detected.

In this study, a research nurse will collect specimens from the penis using a saline wetted
flocculated swab after use of emery paper on the glans penis, coronal sulcus, foreskin (if
uncircumcised) and shaft of penis (entire circumference - dorsal, ventral and lateral).

Laboratory testing for HPV antibody, DNA and mRNA.

Oral, anal and genital specimens will be collected at all visits and tested for HPV DNA and
mRNA. Oral, genital and anal specimens collected at the face to face visits will be placed
in RNAlater so that tests can be performed to determine if HPV transcription is occurring as
indicated by mRNA testing.

Serum will also be collected at each visit for HPV serology.

HPV DNA will be tested using polymerase chain reaction (PCR) with reactive specimens
subjected to linear array to determine HPV genotype.

Testing for other STIs This study will provide an opportunity for potentially studying the
prevalence and factors associated with STIs other than HPV in young MSM who have recently
become sexually active.

Screening for other STIs will also be undertaken at the baseline visit including tests for
urethral and rectal chlamydia, pharyngeal and rectal gonorrhoea, and serology for syphilis
and HIV.

Data analysis

The following will be determined:

- Prevalence of HPV infection at each anatomical site and by each HPV type according to
age. Infections will be grouped as high risk versus low risk and will also be examined
by individual HPV type.

- Specific sexual practices and other factors associated with HPV prevalence.

- Factors associated with HPV deposition versus persistent infection

- The association between mRNA detection and persistent infection.

Definitions for defining outcomes

1. Persistent HPV infection versus deposition Persistent HPV infection: detection of HPV
DNA on at least 2 consecutive occasions at least 6 months apart; HPV deposition:
detection of HPV DNA on one occasion only

2. mRNA testing The role of mRNA testing as an indicator of HPV infection, as distinct
from deposition, will be investigated as part of the study

3. HPV serology Serology for HPV will be undertaken as a further determinant of prevalence
HPV at baseline

Time Frame of up to 12 months The primary outcome is the prevalence of HPV infection at T=0
(enrollment). The prevalence of HPV infection at t=0 is defined as.

1. The detection of the same HPV type at t=0 and t=3 months (i.e. persistent HPV
infection). OR

2. The detection of HPV DNA at t=0 AND the detection of the same HPV type RNA at t=0
(indicating active replication. OR

3. The presence of HPV antibodies to an HPV type at any time up to and including t=12
(because antibodies can take up to 12 months to develop after infection).