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1 These slides are for educational use only. They may not be published, posted online, or used in commercial presentations without prior permission from the presenter.

2 STIs, anal symptoms and anal dysplasia among gay and bisexual men Sian Goddard Tuesday 26th June 2018 Supervisors: David Templeton, Mary Poynten, Kathy Petoumenos

3 Outline SPANC study overview Anal symptoms in GBM Chapter 1: Predictors of anal symptoms Chapter 2: Anal symptoms and HSIL STIs in GBM Chapter 3: STIs in SPANC Chapter 4: Pharyngeal chlamydia Discussion

4 SPANC 4

5 Increasing incidence of anal squamous cell carcinoma (SCC) Age-standardised incidence of anal SCC in Australia between 1982 and Jin F et al. (2009) Vaccine.

6 Anal cancer is concentrated in certain populations Population Relative risk Annual Incidence (per 100,000) General population 1 (referent) 1-2 Women with previous anogenital HPV disease Organ transplant recipients HIV negative Gay and Bisexual men (GBM) HIV positive people (excluding GBM) HIV positive GBM

7 Human Papillomavirus, HSIL and anal SCC 84% of anal cancer is caused by Human Papillomavirus (HPV), which is sexually transmitted Anal HPV infection is common Normal squamous epithelium Infection Progression Invasion Anal high risk Human Papilloma Virus (HPV) Anal high grade squamous intraepithelial lesion (HSIL) Anal SCC Clearance 7 Brickman et al (2015) Curr HIV/AIDS Rep 2015; 12: 6-15

8 Anoscopy and anal dysplasia Anoscopists document abnormalities at each intraanal octant 8 Jay (1997) Dis Colon Rectum Aug;40(8): cite

9 SPANC: Methods 617 men Community recruited HIV-positive and HIVnegative men men who reported previous sex with a man Age 35 years and older Recruited September 2010 to August visits over 3 years: Baseline, 6 months, 12 months, 24 months, 36 months 9 Machalek et al. (2013). BMC Public Health (13)

10 SPANC: Methods Questionnaire: Anal symptoms Sexual behaviours STIs Anal swabs: STI testing Cytology HPV detection/genotyping High resolution anoscopy +/- biopsy 10 Arain S et al (2005). CytoJournal. 2 (4). Darragh T et al (2012). J Low Genit Tract Dis. 16 (3)

11 Baseline cohort characteristics n=617 Median age, years (IQR) 49 (43-56) Lifetime no. of male partners (51.7%) Condomless receptive anal sex past 6 mo (31.3%) HIV positive 220 (35.7%) 11

12 Overview: Anal symptoms 12

13 Anal symptoms may be common BEACH study: 0.7 per 100 GP encounters 1 Half of HIV negative and HIV positive men in a cohort study of HPV prevalence in Sydney reported any anal symptom in the last 12 months 2 High prevalence of anal symptoms among sexual health attendees 3 People are reluctant to report anal symptoms 16% reported anal symptoms to a clinician, versus 75% via questionnaire at Melbourne Sexual Health Clinic 3 HIV positive GBM reporting condomless sex were less likely to discuss anal health with their GP Charles (2010). Aust Fam Physician. 39(6):365; 2 Vajdic (2009) STI 85(5) ; 3 Lister (2008). Sex Health 5(2): 211 ; 4 Rosa-Cunha (2010) AIDS Patient Care STDS. 24 (9)

14 Anal pathology may be common Reports from early in the HIV epidemic describe high rates of anorectal pathology among HIV positive GBM 1 Few published data since anti-retroviral therapy introduced One study found half of HIV positive GBM to have anal pathology at routinely offered anal examination 2 A higher proportion of MSM had anorectal pathology compared to heterosexual men and women (mainly due to warts) 14 1 Wexner et al. (1986) Dis Colon Rectum. 29(11):719-23; 2 Abramowitz (2009) Dis Colon Rectum Jun;52(6)

15 Causes of anal symptoms GBM Possible causes: Receptive sexual practices 40% of over 2700 men attending a Mexican HIV testing centre reported rectal bleeding sometimes during receptive anal intercourse 1 Reported rectal lacerations/fissures from fisting 2 Anal STIs Most STIs are asymptomatic Reported to cause proctitis Sparse data supporting specific symptoms as indicative of STI 3,4 Other anal pathology e.g. haemorrhoids Are anal symptoms clinically useful in predicting STIs or other anal pathology in GBM? What about squamous intra-epithelial lesions? 15 1 Coplan et al (1996). Am J Epidemiology (144) 9; 2 Kazal (1976). Ann Clin Lab Sci. 6 (2); 3 Lister (2008) Sex Health 5 (1) 77-82; 4 Manavi (2004) 15 (3) 162-4

16 Chapter 1 Predictors of anal symptoms Aim: Investigate the prevalence and predictors of anal symptoms among GBM 16 16

17 Anal symptoms: SPANC Questionnaire Anal itch Anal discharge Anal bleeding Pain with defecation Lump in the anus Tearing of the anus Anal sores Feeling that something was left after a bowel movement, defined as tenesmus 17

18 (%) SPANC: Self-reported history of anal symptoms prior to baseline visit Proportion of SPANC participants reporting recent anal symptoms Any anal symptom Tenesmus Bleeding Itch Pain defaecating Last 6 months Last month Last week Lump Tearing Sores Discharge 18

19 Analysis Co-variates: Receptive sexual behaviours: RAI, rimming, fingering, fisting/toy use Anal douching STI: Chlamydia/gonorrhoea/syphilis diagnosed in the last year or at the study visit Anal warts diagnosed in the last year Warts diagnosed at HRA (perianal and/or intra-anal) Lifetime history herpes simplex virus (HSV) Other anal pathology: Fissure/fistula in last 6 months/or diagnosis at HRA Lifetime history of haemorrhoids Haemorrhoids diagnosed at HRA Perianal dermatitis diagnosed at HRA Univariate and multivariate logistic regression analyses with each symptom in the last 6 months as the outcome variable. 19

20 Any anal symptom: Multivariate model n (%) aor (95% CI) p-value Age (34.0) Ref (38.1) 0.68 ( ) (19.3) 0.60 ( ) (8.7) 0.48 ( ) Ever diagnosed with anal herpes simplex virus (HSV) No 18 (11.9) Ref Yes 97 (21.7) 1.89 ( ) Ever diagnosed with haemorrhoids No 66 (42.9) Ref Yes 252 (54.9) 1.65 ( ) Anal warts in the last 12 months No 3 (2.0) Ref Yes 46 (10.2) 4.68 ( )

21 Multivariate analysis: Demographics Decreased likelihood of many symptoms with increasing age Itch Lump Bleeding Age aor (95% CI) p-trend aor (95% CI) p-trend aor (95% CI) p-trend Ref 0.027Ref Ref < ( ) 0.67 ( ) 0.55 ( ) ( ) 0.48 ( ) 0.46 ( ) ( ) 0.33 ( ) 0.25 ( ) Pain with defecation Tearing Any anal symptom Age aor (95% CI) p-trend aor (95% CI) p-trend aor (95% CI) p-trend Ref Ref Ref ( ) 0.71 ( ) 0.68 ( ) ( ) 0.63 ( ) 0.60 ( ) ( ) 0.39 ( ) 0.48 ( ) 21

22 Association between age and symptoms Why? Confounders: Unfactored sexual behaviours? Other STIs? Self-care, e.g. diet Are older people less likely to report symptoms? Published reports vary 1,2 Multiple co-occurring general symptoms reported among older people 3 Biological difference? 22 1 Whitaker K et al (2016) Br J Cancer 114 (3); 2 Nasirian (2015) Int J Health Policy Manag. 5(1); 3 Ritchie (2013) Med Care 51 (10)

23 Multivariate analysis: STIs Chlamydia/Gonorrhoea/Syphilis Syphilis diagnosed within the last year, or at the baseline visit Tearing aor (95% CI) p-value No Ref Yes 2.71 ( ) Chlamydia and Gonorrhoea were not independent predictors of any anal symptom Consistent with reports that anal chlamydia/gonorrhoea are mostly asymptomatic Annan (2009) STI 85(3)

24 Multivariate analysis: STIs HSV Lifetime history of diagnosis of anal herpes simplex virus Itch Sores aor (95% CI) p-value aor (95% CI) p-value No Ref Ref Yes 2.60 ( ) < ( ) <0.001 Pain Any symptom aor (95% CI) p-value aor (95% CI) p-value No Ref Ref Yes 1.68 ( ) ( ) % of men with a lifetime history of HSV were diagnosed >12 months ago 24

25 Multivariate analysis: STIs - Warts Anal warts within the last 12 months Itch Sores Discharge aor (95% CI) p-value aor (95% CI) p-value aor (95% CI) p-value No Ref Ref Ref Yes 2.72 ( ) ( ) ( ) Lump Tenesmus Any symptom aor (95% CI) p-value aor (95% CI) p-value aor (95% CI) p-value No Ref Ref Ref Ref Yes 3.86 ( ) < ( ) ( ) Intra-anal warts at HRA: Itch OR (95% CI) p-trend None Ref octant 1.22 ( ) 2+ octants 2.08 ( ) 25

26 Multivariate analysis: Haemorrhoids Lifetime diagnosis of haemorrhoids Itch Pain with defecation Discharge aor (95% CI) p-value aor (95% CI) p-value aor (95% CI) p-value No Ref Ref Ref Yes 1.67 ( ) ( ) ( ) Lump Bleeding Tearing aor (95% CI) p-value aor (95% CI) p-value aor (95% CI) p-value No Ref Ref Ref Yes 2.67 ( ) < ( ) < ( ) Any symptom aor (95% CI) p-value No Ref Yes 1.65 ( ) 0.01 Haemorrhoids detected at HRA: Not an independent predictor 26

27 Association between haemorrhoids and symptoms The lack of association between clinically detected haemorrhoids and anal symptoms has been reported elsewhere: Riss (2012) detected haemorrhoids at 39% of routine colonoscopies, but only half were symptomatic 1 Due to recurrent disease? Health seeking behaviour and inaccurate diagnosis? Symptoms not dependent on clinical severity? 27 1 Riss (2012) In J Colorectal Dis 27:

28 Multivariate analysis: Other pathology 28 Anal fistula (last 12 months, or at HRA): Lump Discharge Sores aor (95% CI) p-value aor (95% CI) p-value aor (95% CI) p-value No Ref Ref Ref Yes 7.25 ( ) ( ) ( ) Anal fissure (last 12 months, or at HRA): Bleeding aor (95% CI) p-value No Ref Yes 3.05 ( ) Perianal dermatitis : Sores aor (95% CI) p-value No Ref Yes 3.28 ( ) 0.02

29 Multivariate analysis: Receptive Practices Number of receptive anal intercourse partners last 6 months Itch (with condom) Tearing (without condom) aor (95% CI) p-value aor (95% CI) p-value None Ref Ref One 0.89 ( ) 2.17 ( ) 2 or more 0.63 ( ) 2.34 ( ) 29 Receptive fisting/anal toy last 6 months: Discharge aor (95% CI) p-value No Ref Yes ( ) Shelved intra-anal drugs last 6 months Bleeding Pain OR (95% CI) p-value OR (95% CI) p-value No Ref Ref Ref Yes 2.96 ( ) ( ) 0.026

30 Discussion Anal symptoms were common Lack of published literature: suggests this issue is not given enough attention Significant contribution of other anal pathology/sexual/receptive behaviours Anal symptoms may have important consequences: Bleeding has been associated with HIV seroconversion 1 QOL and impact on sexual function Impact on investigation and management of these symptoms e.g. how to differentiate underlying serious pathology/bowel cancer screening 30 1 Coplan (1996) American Journal Epidemiology. 144(9)

31 Chapter 2 Anal symptoms and intra-anal HSIL Aim: Investigate whether anal HSIL is associated with anal symptoms 31 31

32 Anal symptoms and anal HSIL Anal SCC may present with symptoms Cervical HSIL mainly asymptomatic but is associated with abnormal vaginal bleeding High prevalence of HSIL among women referred to colposcopy with abnormal vaginal bleeding 1 Study of > 2 million pap smears in Brazil: Higher likelihood of cervical HSIL if age >30 and documented genital bleeding 2 Whether anal HSIL is associated with symptoms has not been systematically investigated An association between anal discharge and SIL among HIV positive men has been reported 3 Another study no association between any anal symptom and histologically-confirmed HSIL, but HRA not done routinely Rosenthal (2001) 108: ; 2 Xavier-Junior (2015). Acta Obstetricia et Gynecologica Scandinavia. 94 (9); 3 Palefsky (1998) JAIDS 17(4); 4 Hillman (2012) Sexual Health 9 (6)

33 Anal symptoms and HSIL Methods: Composite cytology-histology Anal squamous intraepithelial lesion category n % (95% CI) Composite negative ( ) Composite HSIL ( ) n=414 Other composite diagnoses excluded 33

34 Statistical analyses Logistic regression for association of each anal symptom (last month and last 6 months separately) with composite HSIL (versus composite negative) Any symptom with p<0.1 adjusted for factors previously shown to be independent predictors of HSIL 1 Logistic regression: increasing burden of HSIL (none, 1 octant, 2+ octants) and each anal symptom 34 1 Machalek et al. Papillomavirus Research 2016;2:97-105

35 Anal symptoms within last month Any anal symptom Composite negative n (%) 105 (57.4) Composite HSIL n (%) OR (95% CI) p-value 126 (54.6) 0.89 ( ) Anal discharge 6 (3.3) 10 (4.3) 1.33 ( ) Anal Itch 39 (21.3) 49 (21.2) 0.99 ( ) Anal sores 7 (3.8) 12 (5.2) 1.39 ( ) Anal lump 7 (3.8) 18 (7.8) 2.12 ( ) Pain defecating 24 (13.1) 29 (12.6) 0.95 ( ) Anal bleeding 35 (19.1) 42 (18.2) 0.94 ( ) Anal tearing 10 (5.5) 12 (5.2) 0.95 ( ) Tenesmus 64 (35.0) 69 (29.9) 0.79 ( ) 0.270

36 Anal symptoms within last 6 months Composite negative n (%) Composite HSIL n (%) OR (95% CI) p-value Any anal symptom 135 (73.8) 171 (74.0) 1.01 ( ) Anal discharge 7 (3.8) 15 (6.5) 1.75 ( ) Anal Itch 56 (31.7) 79 (34.2) 1.12 ( ) Anal sores 17 (9.3) 26 (11.4) 1.26 ( ) Anal lump 22 (12.0) 36 (15.6) 1.35 ( ) Pain defecating 37 (20.2) 51 (22.1) 1.12 ( ) Anal bleeding 62 (33.9) 85 (36.8) 1.08 ( ) Anal tearing 23 (12.6) 36 (15.6) 1.28 ( ) Tenesmus 75 (41.0) 92 (39.8) 0.95 ( ) 0.812

37 Adjusted analysis: HSIL and Lump Self-reported anal symptom aor (95% CI) p-value Anal lump last month 2.05 ( ) Number of receptive intercourse partners with condom 1.39 ( ) Number of receptive intercourse partners without condom 1.26 ( ) HIV status 1.62 ( )

38 Burden of HSIL disease Composite negative 183 (48.4%) HSIL 1 octant 124 (32.8%) HSIL 2 + octant 71 (18.8%) TOTAL n=

39 Anal symptoms in last 6 months and HSIL burden OR (95% CI) P-trend Any anal symptom 1.07 ( ) Anal discharge 1.51 ( ) Anal Itch 1.16 ( ) Anal sores 1.24 ( ) Anal lump 1.53 ( ) Pain defecating 1.11 ( ) Anal bleeding 1.09 ( ) Anal tearing 1.18 ( ) Tenesmus 0.92 ( )

40 Anal symptoms in last month and HSIL burden OR (95% CI) P-trend Any anal symptom 1.05 ( ) Anal discharge 1.30 ( ) Anal Itch 1.07 ( ) Anal sores 1.18 ( ) Anal lump 1.93 ( ) Pain defecating 1.04 ( ) Anal bleeding 1.13 ( ) Anal tearing 1.20 ( ) Tenesmus 0.85 ( )

41 Anal lump and self-reported warts HSIL is usually flat; LSIL is usually raised 1 History of anal warts associated with anal lump: Last month: OR 3.93, 95% CI , p<0.001 Last six months: OR 6.15, 95% CI , p<0.001 Adjustment for history of self-reported warts in the last year: Last month: OR 1.71, 95% CI , p=0.070 Last 6 months: OR 1.28, 95% CI , p= Jay (1997) Dis Colon Rectum. 40(8)

42 Discussion The association of anal lump with anal HSIL may be explained by co-existent warts Self-reported history of Composite Composite Sensitivity 12.4% anal warts in the last 12 months Negative HSIL Specificity 99.4% No PPV 96.6% Yes 1 28 NPV 47.8% No association between any other anal symptom As symptoms highly prevalent: may be difficult to detect even if it did exist 42

43 STIs 43

44 Kirby Institute. HIV, viral hepatitis and sexually transmissible infections in Australia: annual surveillance report Sydney: Kirby Institute, UNSW Sydney; 2017; 1 Boffin (2017) BMJ Open. 7 (1); 2 STIs in Older Age Increasing STI notifications Includes older age groups Older people may be less likely to have an adequate sexual history 1 and STI test

45 STI in Older GBM GBM disproportionately affected 1/5 of Gay Community Periodic Survey respondents (2017) reported a recent STI Older GBM may test less frequently with age 1 Majority of older GBM remain sexually active 2 Percentage of Australian gay men and heterosexual women reporting more than one recent sexual partner 45 1 Health Protection Agency (2011). HIV in the United Kingdom.; 2 Poynten et al (2013).Curr Opin Infect Dis. 26 (1)

46 Chapter 3 STIs in SPANC Aims: Investigate the prevalence and incidence of anal chlamydia/gonorrhoea and syphilis Investigate the relationship between age and these STIs in SPANC 46 46

47 STIs in SPANC: Methods STI testing at baseline and annually Clinician collected anal chlamydia/gonorrhoea swabs (NAAT) and syphilis serology Combined self-reported recent history of STI with visit test result Only self-reported history used for syphilis Incidence rates for each infection calculated over 36 month period Multiple failures permitted Cox proportional hazards used to investigate the association between age and incident infection 47 Age, HIV status, sex with casual partners and number of condomless receptive anal intercourse partners added a priori in a multivariate model Other co-variates with p<0.1 at univariate analysis were included and removed in a backward stepwise fashion

48 STIs, sexual behaviours and anal symptoms Incidence of STIs in SPANC Rectal Chlamydia Rectal Gonorrhoea Infectious Syphilis Person years (PY) n Incidence /100 PY 95% CI ( ) ( ) ( ) HIM Study ( ) 1 Also combined interval and study visit diagnoses Anal chlamydia 2-fold and anal Gonorrhoea 3-fold lower Syphilis: 0.49/100 PY On average, 14 years younger HIV positive cohort ( ) 2 Syphilis: 3.62/100 PY 48 1 Jin (2007). STI. 83 (2); 2 Jin (2009) Sexual Health. 6 (4)

49 Interval versus study visit diagnoses Rectal Chlamydia Interval diagnosis n Incidence /100 PY; 95% CI Study visit diagnosis n Incidence /100 PY; 95% CI HIV neg ( ) ( ) HIV pos ( ) ( ) Rectal gonorrhoea HIV neg ( ) ( ) HIV pos ( ) ( ) Syphilis HIV neg ( ) ( ) HIV pos ( ) ( ) Interval diagnoses more frequent than study visit diagnoses: opposite finding to HIM study Suggests more frequent routine screening, particularly among HIV+ 49

50 Multivariate analysis: predictors of STI Anal Chlamydia Anal Gonorrhoea Syphilis Incidence (/100 PY) HR (95% CI) p- value Incidence (/100 PY) HR (95% CI) p- value Incidence (/100 PY) HR (95% CI) p- value Age (years) ( ) ( ) ( ) ( ) ( ) ( ) >= ( ) ( ) ( ) HIV status Negative 6.94 Ref 6.25 Ref Ref Positive ( ) ( ) ( ) URAI partners (6 mo) None < < ( ) ( ) ( ) ( ) ( ) ( ) > ( ) ( ) ( ) Casual partners (6 mo) No Yes ( ) ( ) ( ) Meth & sildenafil (6 mo) No Yes ( ) ( ) Meth, no sildenafil (6 mo) No Yes ( ) ( ) 50

51 Sexual behaviours of SPANC participants 100 Proportion of men reporting any sex in last 6 months % years years years 65+ years 51

52 Sexual behaviours of SPANC participants Proportion of men reporting receptive anal intercourse without condom in the last 6 months Among men who reported RAI in the last 6 months: proportion who reported condomless RAI % Partner number: none % > years years years 65+ years years years years 65+ years 52

53 Discussion Age was not an independent predictor for incident chlamydia/gonorrhoea or syphilis in SPANC SPANC participants remained sexually active Consideration needed to interventions to address the risk of STI among older GBM Guidelines should specifically note the continued risk of STIs in GBM in to older age 53

54 Chapter 4 Pharyngeal Chlamydia Aim: Contrast temporal trend in pharyngeal chlamydia positivity with anogenital chlamydia positivity 54 54

55 Pharyngeal Chlamydia Asymptomatic Prevalence 0.6%-5.4% (1% in HIM) One third of infections spontaneously resolve, but the estimated duration of infection is 667 days 1,2 Transmissible via oral sex 3 1 Chow (2016) Sex Health. 13(3). 2 Van Rooijen (2015). STI. 91 (157-64). 3 Barbee (2016). STI. 92 (2)

56 Pharyngeal STI testing guidelines: Australia Chlamydia and gonorrhoea NAAT for ALL MSM If recent oral sex Gonorrhoea only Doesn t specify

57 Temporal trends in pharyngeal chlamydia Retrospective 1 January December 2014 Standard of care: 3 site testing Laboratory records for all chlamydia testing occasions Excluded repeat testing within 90 days File review of pharyngeal chlamydia cases 57

58 Testing and prevalence Chlamydia testing occasions: number and median age Number of testing occasions Median age Number of testing occasions Age (years) Site Positivity 95% CI Pharynx 1.4% % Rectal 6.1% % 32 Urethra 2.0% %

59 Temporal trends 8 Chlamydia positivity (%): Positivity (%) Pharyngeal Rectal Urethral Pharyngeal chlamydia: OR 1.25 (95% CI ), p-trend: Adjusted for age: aor 1.22 (95% CI ), p-trend:

60 The importance of testing One quarter of pharyngeal chamydia infections and 4.6% of ALL chlamydia infections would not have been treated without pharyngeal testing 60

61 Discussion Increasing pharyngeal chlamydia test positivity between 2011 and 2014 at a sexual health clinic in Sydney Could this be explained by increased testing of asymptomatic men? Unlikely to be related to changing sexual behaviours as no change in urethral/rectal test positivity Most pharyngeal chlamydia is isolated to the pharynx Could even a small number of untreated individuals affect community prevalence? 61

62 Overall: Conclusions First research to investigate both the prevalence and multi-factorial associations of anal symptoms among a community recruited cohort of GBM Anal symptoms are common among GBM and non-sti causes are important First systematic evaluation of the utility of anal symptoms to detect anal HSIL Anal warts/lump may be a useful marker of HSIL/higher burden of HSIL disease in GBM, other symptoms are not useful Anal symptoms: we need to know more 62 Further evaluation of symptoms: frequency/severity Health consequences, including appropriate investigation, management, health economics Opportunity for qualitative work: QOL and impact on sexual experience

63 Overall: Conclusions No other published reports of the incidence of STIs among a cohort of older GBM in the last decade 59 (10%) men were 65 years old in SPANC SPANC participants at significant ongoing risk of STI Age was not an independent predictor Most men in SPANC remained sexually active during study period First published report of increasing pharyngeal chlamydia in Australia Increasing diagnoses of pharyngeal chlamydia Nearly 5% of chlamydia infections would not have been treated without pharyngeal testing Consideration needs to be given to interventions to address the risk of STI among older GBM Guidelines should specifically note the continued risk of STIs in GBM into older age (different to heterosexual men) 63

64 Thank you Supervisors A/Prof David Templeton, Dr Mary Poynten, A/Prof Kathy Petoumenos SPANC study staff and participants HEPP Family and friends 64

65 Acknowledgements Kirby Institute, UNSW St Vincent s Hospital, Sydney University of Sydney Andrew Grulich Carmella Law Kirsten McCaffery Daniel Seeds Mary Poynten Kirsten Howard Marko Garcia Jeff Jin Andrew Carr Patrick Kelly Brian Acraman Garrett Prestage Melbourne Sexual Health Centre Leonie Crampton RPA Sexual Health Patrick McGrath Kit Fairley David Templeton Robert Mellor Piero Pezzopane Douglass Hanly Moir Pathology Kathy Petoumenos Matthew Law Annabelle Farnsworth Royal Women s Hospital, Melbourne Jennifer Roberts Western Sydney Sexual Health Clare Biro Suzanne Garland Adele Richards Sepehr Tabrizi Richard Hillman Julia Thurloe Alyssa Cornall Community representatives Deborah Ekman Samuel Philips Lance Feeney Ross McDonald Dorothy Machalek Russ Gluyas Marjorie Adams The SPANC team thanks the participants. The SPANC study is funded by a NHMRC program grant (# ) and a Cancer Council NSW Strategic Research Partnership Program grant (#13-11). Cytological testing materials are provided by Hologic (Australia) Pty Ltd. The Kirby Institute is affiliated with the Faculty of Medicine, University of New South Wales and funded by the Australian Government of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government.