Transcript Treating Opportunistic Infections Among HIV

Guidelines for Prevention and Treatment of
Opportunistic Infections in HIV-Infected Adults
and Adolescents
Human Papillomavirus Slide Set
Prepared by the AETC National Resource Center
based on recommendations from the CDC,
National Institutes of Health, and HIV Medicine
Association/Infectious Diseases Society of America
About This Presentation
These slides were developed using recommendations
published in May 2013. The intended audience is
clinicians involved in the care of patients with HIV.
Users are cautioned that, because of the rapidly changing
field of HIV care, this information could become out of
date quickly. Finally, it is intended that these slides be
used as prepared, without changes in either content or
attribution. Users are asked to honor this intent.
– AETC National Resource Center
http://www.aidsetc.org
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HPV Disease: Epidemiology
 HPV causes spectrum of anogenital disease, from
warts and condyloma acuminata to squamous cell
cancer
 HPV is the main cause of cervical cancer, also
most anal cancer and some tumors of vulva,
vagina, penis, oral cavity, and oropharynx
 Most HPV infections resolve or become latent
and undetectable
 Tumorigenesis requires persistent infection with
oncogenic HPV type
 Transmitted by sexual contact
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HPV Disease: Epidemiology (2)
 Oncogenic HPV types: 16, 18, 31, 35, at
least 8 others
 Type 16 accounts for ~50% of cervical
cancers and most noncervical cancers in the
general population; HPV18 accounts for 1015% of cervical cancers
 Types 6 and 11 associated with 90% of
genital warts
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HPV Disease: Epidemiology (3)
Cervical dysplasia and cancer:
 In women with HIV infection
 Higher rates of cervical cancer
 Higher rates of:
 HPV infection
 Oncogenic HPV types
 Cervical intraepithelial neoplasia (CIN)
(low grade and high grade)
 Increased risk with lower CD4 cell counts
 Vulvar and vaginal intraepithelial neoplasia
also more common
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HPV Disease: Epidemiology (4)
Anal dysplasia and cancer:
 In women and men with HIV infection
 Higher incidence of anal cancer
 Higher rates of anal intraepithelial neoplasia
(AIN)
 Higher risk of anal cancer with lower CD4
counts
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HPV Disease: Epidemiology (5)
Genital and anal warts:
 Incidence and prevalence are higher in
HIV-infected patients
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HPV Disease: Epidemiology (6)
 Impact of ART on incidence of HPV-associated
cancers is not clear; may differ by tumor type
 Limited evidence that ART may decrease progression
of CIN
 No overall change in incidence of cervical cancer
since introduction of ART, and anal cancer rates are
increasing
 Incidence of low-grade VIN lesions and anogenital
warts lower with ART, though rate of high-grade VIN
unchanged
 Conflicting data re impact of ART on oral warts –
some, but not all, studies report increased rates
after ART initiation
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HPV Disease: Epidemiology (7)
 HPV vaccine:
 Use in adolescents and young adults may
reduce risk of cancers caused by HPB 16 and
18 in HIV-infected people later in life
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HPV Disease: Clinical Manifestations
and Diagnosis
Warts: genital, anal, and oral
 Usually flat, papular, or
pedunculated growths on
mucosa or epithelium, 2 mm to
2 cm, may occur in clusters
 Often asymptomatic; may
cause itching or discomfort
 Diagnosis: visual inspection;
biopsy if uncertain diagnosis
 HPV DNA: no data support use for
routine diagnosis or management
Condyloma acuminata, perianal
Credit: P. Volberding, MD; UCSF Center
for HIV Information Image Library
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HPV Disease: Clinical Manifestations
and Diagnosis (2)
Cervical and vaginal intraepithelial neoplasia (CIN,
VIN) and squamous cell cancers
 No characteristic symptoms; often asymptomatic,
may present with bleeding or mass
 Screening:
 Visual inspection of entire anogenital area
 Pap test
 Cytology (Pap) and colposcopy techniques as in HIVuninfected women
 Digital examination of vaginal, vulvar, perianal regions,
and anal canal to feel for masses
 High-resolution colposcopy and biopsy as needed
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HPV Disease: Clinical Manifestations
and Diagnosis (3)
Anal, vulvar, and vaginal intraepithelial neoplasia;
oral HPV disease
 No characteristic symptoms; often asymptomatic,
may present with bleeding or itching; external
lesions may be visible or palpable
 Screening:




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Visual inspection
Anal cytology
Digital examination to feel for masses
High resolution anoscopy as needed
Biopsy of suspicious lesions
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HPV Disease: Clinical Manifestations
and Diagnosis (4)
Role of HPV testing
 Role of cervical HPV testing for HIV-infected
women has not been established
 Some specialists recommend HPV testing for triage
of women with ASC-US, as in HIV-uninfected women
 Utility uncertain, given high prevalence of oncogenic HPV in
HIV-infected women
 Anal and other noncervical specimens: no
recommendation
 Prior to HPV vaccination: no recommendation
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HPV Disease: Preventing Infection
Vaccination
 HPV vaccines (quadrivalent and bivalent), prevent
HPV 16 and 18 cervical, vaginal, and vulvar
infections, precancers, and cancers in females
 Quadrivalent vaccine also prevents
 HPV 16 and 18 anal infections and precancers
 HPV 6 and 11 infections
 No efficacy data in HIV-infected individuals (studies
ongoing), though quadrivalent vaccine shown to be
safe and immunogenic
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HPV Disease: Preventing Infection (2)
 HPV vaccine (bivalent or quadrivalent) is strongly
recommended for HIV-infected girls aged 9-12 years
 Also recommended for HIV-infected females aged 13-26
years
 Quadrivalent vaccine is strongly recommended for
HIV-infected boys aged 9-12 years
 Also recommended for HIV-infected males aged 13-26
years
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HPV Disease: Preventing Infection (3)
 Vaccination ideally should precede sexual exposure
to HPV; likely to be less effective in persons aged
19-26 because they already may have acquired
HBV 6, 11, 16, or 18
 Data insufficient to recommend vaccination for those
aged >26; HPV vaccines not approved for age >26
 HIV-infected women who have been vaccinated
should have routine cervical cancer screening
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HPV Disease: Preventing Infection (4)
Condom use
 Use of male latex condoms is strongly
recommended for preventing transmission
or acquisition of HPV
 Associated with lower rates of HPV infection
 If male condoms cannot be used properly, a female
condom should be considered
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HPV Disease: Preventing Infection (5)
Male circumcision
 Lower rates of oncogenic HPV infection of the penis
 In the general population, lower risk of penile cancer
and of cervical cancer in sex partners (data from
observational studies)
 In HIV-infected men, limited data suggest effect is
protective but to lesser degree
 Effect on genital, anal, or oral HPV-related cancer or
precancer in HIV-infected men or their sex partners not
known
 In the U.S., insufficient evidence to recommend adult male
circumcision for the purpose of reducing risk of
oncogenic HPV infection
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HPV Disease: Preventing Disease –
Cervical Cancer
 For all HIV-infected women who have initiated sexual
activity: screening Pap at 6-month intervals in first year
after HIV diagnosis; annually thereafter if results are
normal
 Consider screening within 1 year of sexual activity,
regardless of age or mode of HIV infection
 High rate of progression of abnormal cytology in HIVinfected adolescents and young women who were infected
via sex; high rate of cervical abnormalities in perinatally
infected adolescents
 Annual screening should continue for life: HIV-infected
women remain at risk of development of cervical
cancer
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HPV Disease: Preventing Disease –
Cervical Cancer
(2)
 If abnormal Pap result, care generally should be
provided according to American Society for
Colposcopy and Cervical Pathology (ASCCP)
guidelines
 Exception: in HIV-infected women, HPV testing alone
is not recommended for follow-up of an abnormal Pap
test
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HPV Disease: Preventing Disease –
Cervical Cancer (3)
Management of abnormal results
 ASC-US
 Immediate referral for colposcopy or repeat cytology in
6-12 months
 Greater than ASC-US (ASC-H, LSIL, or HSIL)
 Refer for colposcopy
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HPV Disease: Preventing Disease –
Vaginal and Vulvar Cancer
 Women with history of high-grade CIN or cervical
cancer: regular vaginal cuff Pap test
 Routine screening not recommended after hysterectomy
for benign disease in absence of prior CIN 2-3 or cancer
 Abnormal vaginal Pap results: vaginal colposcopy
with Lugol iodine solution
 Concomitant cervical and vulvar lesions: vaginal
colposcopy
 No available screening procedure for vulvar
cancer; biopsy or refer if suspected lesions
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HPV Disease: Preventing Disease –
Anal Cancer
 No national recommendations for routine
screening; some specialists recommend anal
cytologic screening of all HIV-infected men and
women:
 Annual digital rectal exam for masses
 Management of abnormal anal Pap results
 ASC-US, ASC-H, LSIL, or HSIL: high-resolution
anoscopy
 Biopsy of visible lesions
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HPV Disease: Treatment – Genital and
Oral Warts
 In HIV infection, warts may be larger or more
numerous, may not respond well to therapy,
and may recur more frequently
 No uniformly effective or preferred
 For intra-anal, vaginal, or cervical warts, refer
to a specialist
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HPV Disease: Treatment – Genital and
Oral Warts (2)
 Patient-applied treatment
 For uncomplicated external warts
 Podophyllotoxin (e.g., podofilox 0.5% solution or
0.5% gel) applied to lesions BID for 3 days,
followed by 4 days of no therapy, repeated weekly
for up to 4 weeks
 Imiquimod 5% cream applied to lesions at bedtime
and washed off in morning, 3 nonconsecutive
nights per week for up to 16 weeks
 Sinecatechins 15% ointment applied to area TID
for up to 16 weeks
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HPV Disease: Treatment – Genital and
Oral Warts (3)
 Provider-applied treatment
 For complex or multicentric lesions, or lesions
inaccessible to patient
 Cryotherapy (liquid nitrogen or cryoprobe),
repeat every 1-2 weeks for up to 4 weeks
 Trichloroacetic or bichloroacetic acid 80-90%
aqueous solution to lesions, repeat weekly for up
to 6 weeks
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HPV Disease: Treatment – Genital and
Oral Warts (4)
 Provider-applied treatment (cont’d)
 Surgical excision or laser surgery
 Podophyllin resin 10-25% in tincture of benzoin;
weekly for up to 6 weeks
 Other treatments: consider if above are not
effective:
 Topical cidofovir (not available commercially)
 Intralesional interferon not recommended
 Oral warts: surgical treatment is most common;
many topicals cannot be used on oral mucosa
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HPV Disease: Treatment – CIN and
Cervical Cancer
 Manage with a specialist
 Follow ASCCP guidelines, in general
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HPV Disease: Treatment – CIN and
Cervical Cancer (2)
 High-grade CIN:
 Satisfactory colposcopy: ablation or excision
 Unsatisfactory colposcopy: excision
 Recurrent high-grade CIN: diagnostic excisional
methods; hysterectomy is acceptable
 Invasive cervical, vaginal, vulvar cancer
 Follow National Comprehensive Cancer Network
guidelines
 Standard treatment appears safe and effective
 Complication and failure rates may be higher in HIVinfected women
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HPV Disease: Treatment – CIN and
Cervical Cancer (3)
 HIV-infected adolescents
 Follow ASCCP guidelines for adolescents and
young women
 Progression and recurrence of lesions is more
common
 For CIN 1 and CIN 2, consider close observation
(per guidelines recommendations)
 If compliance is questionable, may be preferable to
follow the treatment arm of management for CIN 2
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HPV Disease: Treatment – VIN, VAIN, Vulvar
and Vaginal Cancers
 Consult with specialists; individualize care
 Low-grade VIN/VAIN: can observe or manage
as for vulvovaginal warts
 VIN: local excision, laser vaporization, ablation,
imiquimod
 VAIN: topical 5-fluorouracil (5-FU), laser
vaporization, excision
 Vulvar and vaginal cancer: individualize care,
follow National Comprehensive Cancer
Network guidelines
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HPV Disease: Treatment – AIN and Anal
Cancer
 Insufficient data to recommend specific
treatment approaches
 Choice of treatment based on size and location
of lesion, histologic grade
 Options for AIN:
 Infrared coagulation has moderate efficacy for AIN 2
or 3 in HIV-infected patients
 Others: topical 5-FU, cryotherapy, laser therapy,
surgical excision
 Local TCA has been used for AIN; intra-anal imiquimod
shows moderate efficacy for intra-anal AIN
 Anal cancer: consult with specialist; combination
radiation and chemotherapy used most
commonly
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HPV Disease: Treatment – Other HPVAssociated Cancers
 HPV-associated penile and oropharyngeal
cancers: as in HIV-uninfected patients
 Prognosis may be better with HPV-associated
oropharyngeal cancers than with non-HPVassociated
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HPV Disease: Starting ART
 To date, no data show that ART initiation should
be influenced by presence of HPV-related
disease
 Some studies found decreased persistence and
progression of CIN during ART, but no change
in incidence of cervical cancer, and anal cancer
incidence has increased
 No data show that treatment for CIN or AIN
should be modified for patients on ART or that
ART should be started or modified for treatment
of CIN or AIN
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HPV Disease: Monitoring and Adverse
Events
 Increased risk of recurrence of CIN and
cervical cancer in HIV-infected patients
 Frequent cytologic screening and
colposcopy according to guidelines
 No IRIS has been described in
association with HPV infections
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HPV Disease: Monitoring and Adverse
Events (2)
 All treatment modalities have risk of adverse
effects: monitor by physical exam and symptom
review during and after treatment
 Ablative and excisional modalities: pain,
discomfort, intraoperative or postoperative
bleeding, infection, cervical stenosis
 AIN treatments may cause pain, bleeding,
ulceration; rarely abscesses, fissures, or fistulas
 Anal cancer treatment (radiation + chemotherapy)
associated with high rate of morbidity, including
proctitis
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HPV Disease: Treatment Failure
 Persistence or recurrence of lesions after
appropriate therapy
 For genital warts, consider retreatment with
any modality listed above; >1 course of therapy
often needed
 Consider biopsy to rule out VIN
 For persistent or recurrent CIN, manage
according to ASCCP guidelines
 VIN: no consensus; consider surgical excision
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HPV Disease: Preventing Recurrence
 Monitoring after therapy:
 CIN: follow ASCCP guidelines
 For high-grade CIN, low-dose intravaginal 5-FU
reduced short-term risk of recurrence in one
study; no recommendation for use
 VIN: no guidelines; twice-yearly vulvar
inspection appears reasonable
 High-grade VIN: manage as with CIN 2 (cytology
at 6 and 12 months after treatment, annually
thereafter)
 No indication for secondary prophylaxis
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HPV Disease: Considerations in
Pregnancy
 Genital warts or anogenital HPV-related
neoplasia: manage with team of specialists (eg,
OB/GYN and infectious disease)
 Warts: frequency and rate of growth may be
greater during pregnancy
 Podophyllin and podofilox should not be used: risk of
fetal death
 Imiquimod: insufficient data to recommend during
pregnancy
 Other topical treatments (eg, BCA, TCA) and ablation
can be used
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HPV Disease: Considerations in
Pregnancy (2)
 Transmission of genital HPV 6 and 11 at delivery
may cause recurrent laryngeal papillomatosis in
infants, but no change in obstetrical management
is indicated for women with HPV infection (unless
extensive lesions that may impede vaginal
delivery or cause extensive bleeding)
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HPV Disease: Considerations in
Pregnancy (3)
 All pregnant women should have Pap screen at
initial prenatal visit (unless normal Pap within 1 year)
 Abnormal cervical cytology: colposcopy with biopsy of
suspicious lesions
 Cytobrush sampling can be done; endocervical curettage
should not be done
 ASC-US: manage as in nonpregnant women, except
may defer colposcopy until ≥6 weeks postpartum
 CIN: treatment not recommended during pregnancy,
unless invasive disease; reevaluate with cytology
and colposcopy after 6 weeks postpartum
 Vaginal delivery appropriate, if no contraindications
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HPV Disease: Considerations in
Pregnancy (4)
 Suspected cervical cancer: refer to
gynecological oncologist for definitive
diagnosis, treatment, delivery plan
 AIN: effects of treatment on pregnancy are
not known
 Most experts recommend deferral of diagnosis
and treatment until after delivery, unless strong
suspicion of anal cancer
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HPV Disease: Considerations in
Pregnancy (5)
 HPV vaccines: not recommended during
pregnancy, though available data do not
show negative effect on pregnancy
outcomes
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Websites to Access the Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov
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About This Slide Set
 This presentation was prepared by Susa Coffey,
MD, for the AETC National Resource Center in
May 2013.
 See the AETC NRC website for the most current
version of this presentation:
http://www.aidsetc.org
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