Cervical cancer screening


Clinical question list[edit source]

Questions 1[edit source]

Relevant guidelines content page: Oncogenic HPV types not 16/18

Question 1a[edit source]

Primary PICO

For women who are positive for hr-HPV types other than 16 or 18 and have pLSIL/dLSIL reflex liquid based cytology (intermediate risk), what is the safety and effectiveness of immediate colposcopy compared to colposcopy delayed by 12 months based on later HPV test results (assuming referral to colposcopy if any HPV positive at 12 months)?

Population Study design Intervention Control Outcome
Women who are positive for hr-HPV types other than 16 or 18 and have pLSIL/dLSIL (ASC-US/LSIL) liquid based cytology (intermediate risk) Randomised or pseudo randomized controlled trial Immediate

Colposcopy

Repeat HPV test in 12 months;

Colposcopy if positive

Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

Secondary PICO (In the event that no randomised or pseudo-randomised controlled trials were identified that directly addressed the primary PICO)

For women undergoing routine cervical screening what is the risk of CIN3+ for women who are positive for HPV oncogenic types other than 16 and 18 and have p/dLSIL cytology compared with women who have p/d LSIL cytology regardless of HPV status, p/dHSIL cytology regardless of HPV status, or are HPV 16/18+ regardless of cytology?

Population Study design Exposure Comparator Outcome
Women undergoing routine cervical screening Longitudinal or cross-sectional prognostic Positive for HPV oncogenic types other than 16 and 18 and have p/dLSIL cytology p/dLSIL or

p/dHSIL or

HPV 16/18+

CIN3+

CIN2+

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Question 1b[edit source]

Primary PICO

For women who are positive for hr-HPV types other than 16 or 18 and have negative or pLSIL/dLSIL reflex liquid based cytology (intermediate risk), what is the safety and effectiveness of repeating HPV testing in 12 and 24 months compared to repeating HPV test at 12 months only before returning to 5 yearly screening?

Population Study design Intervention Control Outcomes
Women who are positive for hr-HPV types other than 16 or 18 and have negative or pLSIL/dLSIL (ASC-US/LSIL) liquid based cytology (intermediate risk) Randomized or pseudo randomized controlled trial Repeat HPV test in 12 and 24 months;

Colposcopy and reflex LBC if positive or if both negative discharge back to screening

Repeat HPV test in 12 months; Colposcopy if positive and if negative discharge to screening Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

Secondary PICO (In the event that no randomised or pseudo-randomised controlled trials were identified that directly addressed the primary PICO)

For women undergoing routine cervical screening what is the risk of subsequent CIN3+ for women who are positive for HPV oncogenic types other than 16 and 18 and have negative cytology compared with women who have p/d LSIL regardless of HPV status or who have p/d LSIL and are positive for HPV oncogenic types other that 16 and 18?

Population Study design Exposure Comparator Outcomes
Women undergoing routine cervical screening Longitudinal prognostic Positive for HPV oncogenic types other than 16 and 18 and have NILM cytology p/dLSIL

or

positive for HPV oncogenic types other than 16 /18 and have p/dLSIL cytology

CIN3+

CIN2+

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Questions 2[edit source]

Relevant guidelines content page: Normal colposcopic findings following LBC prediction of LSIL or HSIL

Question 2a[edit source]

Primacy PICO

For HPV positive women who are not in treatment follow-up and who have negative or LSIL cytology and who have undergone colposcopy and the colposcopy was negative, what is the safety and effectiveness of testing with repeat HPV test at 12 months when compared with repeat cytology and HPV testing in 12 months?

Population Study design Intervention Control Outcomes
HPV positive women who have undergone colposcopy and the colposcopy was negative and cytology was:

i. negative,

ii. p/d LSIL

Randomized or pseudo randomized controlled trial Repeat HPV test at 12 months;

Colposcopy (and reflex LBC test) if positive

If negative HPV test in 12 months

Repeat cytology and HPV testing at 12 months: Colposcopy if HPV positive test or if cytology pHSIL or worse, and another 12 months follow-up if HPV negative p/dLSIL; repeat HPV and cytology test in 12 months if HPV negative and cytology p/dLSIL or negative Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection


Secondary PICO (In the event that no randomised or pseudo-randomised controlled trials were identified that directly addressed the primary PICO)

For HPV positive women who are not in treatment follow-up and who have negative or p/dLSIL cytology on referral and who had colposcopy and the colposcopy was negative what are the predictors of subsequent detection of high-grade disease?

Population Study design Exposure Comparator Outcomes
Women who have p/dLSIL or negative cytology who have undergone colposcopy and no abnormalities were seen on colposcopy Cohort Referral cytology

Referral HPV status

Age

Other

Referral cytology

Referral HPV status

Age

Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

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Question 2b[edit source]

For women who are HPV positive with p/dHSIL referral cytology and p/dLSIL or less after cytologic review and colposcopy is negative, what is the safety and effectiveness of conservative management compared with excision of the transformation zone?

Population Study design Intervention Control Outcome
HPV positive women who have undergone colposcopy and the colposcopy was negative and referral cytology was p/d HSIL and review cytology was p/d LSIL or less Randomized or pseudo randomized controlled trial Conservative management Excision of the transformation zone Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

dHSIL = definite HSIL; dLSIL = definite LSIL; HSIL = high-grade squamous intraepithelial lesion; LSIL = low-grade squamous intraepithelial lesion pHSIL = possible HSIL; pLSIL = possible LSIL

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Question 2c[edit source]

For women who are HPV positive with p/dHSIL referral cytology and p/dHSIL after cytologic review and colposcopy is negative, what is the safety and effectiveness of cytologic and colposcopic follow-up at 3-6 months compared with excision of the transformation zone?

Population Study design Intervention Control Outcome
HPV positive women who have undergone colposcopy and the colposcopy was negative and referral and review cytology was p/d HSIL Randomized or pseudo randomized controlled trial Conservative management; cytologic and colposcopic follow-up at 3-6 months Excision of the transformation zone Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

dHSIL = definite HSIL; HSIL = high-grade squamous intraepithelial lesion; pHSIL = possible HSIL

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Questions 3[edit source]

Relevant guidelines content page: Type 3 TZ (previously termed ‘unsatisfactory’) colposcopy following LBC prediction of LSIL or HSIL


Question 3a[edit source]

For HPV positive women currently not in treatment follow-up and have negative or LSIL cytology who have undergone colposcopy and the colposcopy was unsatisfactory what is the safety and effectiveness of repeat HPV test at 12 months compared with repeat cytology and HPV testing in 12 months?

Population Study design Intervention Control Outcomes
HPV positive women who have undergone colposcopy and the colposcopy was unsatisfactory

and cytology was:

i. negative,

ii. p/d LSIL

Randomized or pseudo randomized controlled trial Repeat HPV test at 12 months; Colposcopy (and reflex LBC test) if positive and if negative HPV test in 12 months Repeat cytology and HPV testing at 12 month; Colposcopy if HPV positive test or if cytology pHSIL or worse, and another 12 months follow-up if HPV negative p/dLSIL; repeat HPV and cytology test in 12 months if HPV negative and cytology p/dLSIL or negative Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

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Question 3b[edit source]

For HPV-positive women with a referral cytology finding of p/dHSIL and who have an unsatisfactory colposcopy, what is the safety and effectiveness of conservative management compared with diagnostic excision of the transformation zone?

Population Study design Intervention Control Outcomes
HPV positive women who have undergone colposcopy and the colposcopy was unsatisfactory

and cytology was:

p/d HSIL

Randomized or pseudo- randomized controlled trial Conservative management:

Co-testing at 3-6 months or repeat HPV test at 12 months

Diagnostic excision of the transformation zone Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

dHSIL = definite HSIL; HSIL = high-grade squamous intraepithelial lesion; pHSIL = possible HSIL

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Question 4[edit source]

Relevant guidelines content page Chapter 9. Management of histologically confirmed low-grade squamous abnormalities


For HPV positive women currently not in treatment follow-up who have undergone colposcopy (without treatment) with colposcopy LSIL and CIN 1 or less on biopsy what is the safety and effectiveness of excisional treatment or testing with repeat HPV test at 12 months when compared with repeat cytology and HPV testing in 12 months?

Population Study design Intervention Control Outcomes
HPV positive women, who have undergone colposcopy and colposcopy LSIL, confirmed by biopsy CIN1 or less,

and referral cytology was:

i. negative or p/d LSIL

or

ii. p/dHSIL

Randomized or pseudo randomized controlled trial Excisional treatment

or

Repeat HPV test at 12 months

i. Negative cytology or p/dLSIL: Repeat cytology and HPV testing at 12 months: Colposcopy if HPV positive test or if cytology pHSIL or worse, and another 12 months follow-up if HPV negative p/dLSIL; repeat HPV and cytology test in 12 months if HPV negative and cytology p/dLSIL or negative

ii. p/dHSIL: repeat cytology and colposcopy in 6 months

Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

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Questions 5[edit source]

Relevant guidelines content page: Investigation of cytological glandular abnormalities

Question 5a[edit source]

For women who are HPV positive with atypical endocervical cells of undetermined significance (confirmed on review) and negative colposcopy what is the safety and effectiveness of repeating HPV and cytology testing when compared with treatment with excisional cone biopsy?

Population Study design Intervention Control Outcomes
Women who are HPV positive with atypical endocervical cells of undetermined significance (confirmed on review) and colposcopy negative Randomized or pseudo randomized controlled trial Repeat HPV and liquid based cytology testing at 6 months Excisional cone biopsy cervix Cervical cancer mortality

Other gynaecologic cancer diagnosis (endometrial, ovarian)

Cervical cancer diagnosis

Precancerous high grade lesion (including AIS) detection

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Question 5b[edit source]

For women who are HPV positive with atypical glandular cells of undetermined significance (AGUS) or possible high grade glandular lesion (confirmed on review) and negative colposcopy what is the safety and effectiveness of repeating HPV and cytology testing when compared with treatment with excisional cone biopsy?

Population Study design Intervention Control Outcomes
Women who are HPV positive with AGUS or possible HGGA (confirmed on review) and colposcopy negative Randomized or pseudo randomized controlled trial Repeat HPV and liquid based cytology testing at 6 months Excisional cone biopsy cervix Cervical cancer mortality

Cervical cancer diagnosis

Endometrial cancer diagnosis

Ovarian cancer diagnosis

Precancerous high grade lesion (including AIS) detection

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Question 6[edit source]

Relevant guidelines content page: Treatment of HSIL CIN2

For women with biopsy confirmed CIN2 what is the safety and effectiveness of p16 immunohistochemistry and treating only p16 positive CIN2 while conservatively managing p16 negative CIN2 when compared with treating all CIN2 cases?

Population Study design Intervention Control Outcomes
Women with biopsy confirmed CIN2 Randomized or pseudo randomized controlled trial Using p16 immunohistochemistry to stratify management:

p16 positive cases treated with excision and p16 negative cases conservatively managed

Treat all CIN2 with excision of transformation zone. Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

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Question 7[edit source]

Relevant guidelines content page: Follow-up after excisional treatment for AIS

For women who are HPV positive with adenocarcinoma in situ (AIS) or possible high-grade glandular lesion cytology or biopsy confirmed AIS, what is the safety and effectiveness of large loop excision of the transformation zone (LLETZ), Fischer cone, laser cone or straight wire/needle excision of the transformation zone (SWETZ/NETZ) compared with cold knife cone biopsy?

Population Study design Intervention Control Outcomes
Women who are HPV positive with AIS or possible high-grade glandular lesion cytology or biopsy confirmed AIS Randomized or pseudo randomized controlled trial LLETZ or

Fischer cone or

laser cone or

SWETZ or

NETZ or

Any electro-surgery of the transformation zone

Cold knife cone biopsy Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion (including recurrent AIS) detection

Completeness of excision.

Depth of excision

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Question 8[edit source]

Relevant guidelines content page: Investigation of abnormal vaginal bleeding

For women with postcoital, intermenstrual bleeding or heavier periods (menorrhagia), what is the safety and effectiveness of direct colposcopy compared with HPV test and cytology?

Population Study design Intervention Control Outcomes
Women with postcoital (PCB) or intermenstrual bleeding (IMB) or menorrhagia Randomized or pseudo randomized controlled trial Direct referral to colposcopy Cytology and HPV Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

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Question 9[edit source]

Relevant guidelines content page: Screening in immune-deficient women

For women who are at higher risk of cervical cancer due to immunosuppression what is the safety and effectiveness of screening using strategies other than those recommended for the general population compared to those recommended for the general population?

Population Study design Intervention Control Outcome
Chronically immuno-suppressed or immuno-compromised asymptomatic women

or

Potentially immune suppressed or immune compromised women

Screening randomized controlled or pseudo- randomized trial Modified recommended screening strategy:

starting at an age <25 years and/or screening intervals less than 5 years and/or referring all HPV positive women to colposcopy irrespective of reflex cytology result

Recommended screening strategy

Primary HPV screening every 5 years from ages 25 – 69 years using partial genotyping with women positive for HPV16/18 referred to colposcopy and women positive for other oncogenic types undergoing cytology triage

Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

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Question 10[edit source]

Relevant guidelines content page: Women who have experienced early sexual activity or have been victims of sexual abuse

For women with a history of sexual abuse or early sexual debut what is the safety and effectiveness of screening using strategies other than those recommended for the general population compared to those recommended for the general population?

Population Study design Intervention Control Outcome
History of sexual abuse or early sexual debut Screening randomized or pseudo- randomized controlled trial Modified recommended screening strategy:

Starting at an age <25 years

Recommended screening strategy

Primary HPV screening every 5 years from ages 25 – 69 years using partial genotyping with women positive for HPV16/18 referred to colposcopy and women positive for other oncogenic types undergoing cytology triage

Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

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Question 11[edit source]

Relevant guidelines content page: Screening in DES-exposed women

For women who were exposed to diethylstilboestrol (DES) in utero and their daughters what is the safety and effectiveness of screening using strategies other than those recommended for the general population compared to those recommended for the general population?

Population Study design Intervention Control Outcome
Asymptomatic women exposed in utero to DES and their daughters Screening randomized or pseudo- randomized controlled trial Current practice: Annual vaginal examination, cervical and vaginal cytology test, HPV test and colposcopy of the lower genital tract Recommended screening strategy for general population:

Primary HPV screening every 5 years from ages 25 – 69 years using partial genotyping with women positive for HPV16/18 referred to colposcopy and women positive for other oncogenic types undergoing cytology triage

Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

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Question 12[edit source]

Relevant guidelines content page: Screening in Aboriginal and Torres Strait Islander women

For women who are of Aboriginal or Torres Strait Islander descent what is the safety and effectiveness of screening using strategies other than those recommended for the general population compared to those recommended for the general population?

Population Study design Intervention Control Outcomes
Women of Aboriginal or Torres Strait Islander descent Screening randomized or pseudo-randomized controlled trial Modified recommended screening strategy:

- starting at an age <25 years

- other

Recommended screening strategy for general population:

Primary HPV screening every 5 years from ages 25 – 69 years using partial genotyping with women positive for HPV16/18 referred to colposcopy and women positive for other oncogenic types undergoing cytology triage

Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

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Question 13[edit source]

Relevant guidelines content page: Screening in pregnancy

For women who are pregnant update the literature of management of abnormal cytology in pregnancy p.74 from the old guidelines. Describe guidance for excluding presence of invasive cancer. How can we support the exclusion of the presence of the invasive cervical cancer? Are there any circumstances that you would manage or treat pregnant women differently to the general population?

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Questions 14[edit source]

Relevant guidelines content page: After total hysterectomy

For groups of women (literature review or PICO) who have had a hysterectomy. What should the recommendation be in regard to further ‘screening’?

  1. Women with total hysterectomy for benign conditions who have never had an abnormal HPV or cytology. Do they need any further screening?
  2. Women who have had in the past been HPV positive with high grade abnormality (squamous or glandular) who have been treated satisfactorily and are on surveillance or have returned to normal screening, who then have a total hysterectomy with no evidence of abnormality on the hysterectomy specimen.
  3. Women who have had a high grade abnormality treated by total hysterectomy, with complete excision of the lesion in the hysterectomy specimen. What follow up would be reasonable.
  4. Women who have had a high grade lesion (CIN2+) who have been treated and have completed test of cure and returned to routine screening, subsequently have hysterectomy with no abnormality in the hysterectomy specimen. Is there any need for further screening?

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Question 16[edit source]

Relevant guidelines content page: Test of Cure after treatment for HSIL (CIN2/3)

For women have been treated for a high grade precancerous squamous lesion what is the safety and effectiveness of testing with HPV test and cytology at 12 months after treatment and discharging if double-negative compared with testing at 12 and 24 months and discharging if double-negative at both 12 and 24 months?

Population Study design Intervention Control Outcome
Women who have been treated for high grade precancerous squamous lesions Randomized or pseudo randomized controlled trial Cytology and HPV testing 12 months after treatment with discharge if double negative Cytology and HPV testing 12 and 24 months after treatment with discharge if double negative on both occasions Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion detection

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Question 17[edit source]

Relevant guidelines content page: Follow-up after excisional treatment for AIS

For women have been treated for adenocarcinoma in situ (AIS) with cone excision or LEEP and with clear histologic margins what is the safety and effectiveness of cytology and HPV testing at 12 and 24 months and discharging if double-negative at both 12 and 24 months or completion hysterectomy compared to cytology?

Population Study design Intervention Control Outcome
Women treated for AIS with cone excision or LEEP with complete excision and clear histological margins Randomized or pseudo randomized controlled trial Cytology and HPV testing 12 and 24 months after treatment with discharge if double negative on both occasions

Or

Completion hysterectomy

Annual cytology Cervical cancer mortality

Cervical cancer diagnosis

Precancerous high grade lesion (including recurrent AIS) detection

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