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Preventing Cervical Cancer

OBGYN Clerkship

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Objectives

Session Level Objectives (SLO) 22:

Discuss an approach to screening for HPV infection, cervical dysplasia and neoplasia.
Discuss investigation and management of cervical dysplasia including the role of colposcopy.

Dr. Sabourin’s Personal Objective: HELP YOU PREVENT CERVICAL CANCER!!

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KNOW THE USUAL NATURAL HISTORY

Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):553-60

2-5 years

10+ years

HSIL

(high grade)

Normal

HPV

Infection

Precancer

Cancer

Infection

Clearance

Regression

Progression

Invasion

Persistence

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KNOW THE USUAL NATURAL HISTORY

Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):553-60

Most of the time: HPV infections clear, low grade dysplasia regresses

2-5 years

10+ years

HSIL

(high grade)

Normal

HPV

Infection

Precancer

Cancer

Infection

Clearance

Regression

Progression

Invasion

Persistence

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SEE THE NATURAL HISTORY

COLPOSCOPY

Colpo info and videos for Alberta

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https://www.instagram.com/reel/DafIAn5ooWr/?igsh=ZGUzMzM3NWJiOQ==

Patients at risk of HSIL are referred
Targeted biopsies are done
Biopsies make the diagnosis: Is there high grade dysplasia/cancer

X Not used to monitor/screen for progression

Paps/HPV testing does this well (cheaper, less intensive/invasive)
Most cases to do not progress

This is a great summary about colposcopy that you can look at if you are interested or coming to a clinic.

Patients that are identified at risk of having high grade dysplasia in the cervical cancer screening program are referred for colposcopy.

Colposcopy uses different light intensities, magnifications and filters along with acetic acid (vinegar) and Lugol’s iodine to identify normal and abnormal areas.

Targeted biopsies are done to confirm the impression and document if high grade dysplasia is present.

It is NOT used to surveil/monitor or screen for progression from HPV infection or low grade changes to high grade precancer. 🡪Paps and HPV test do that well and are cheaper, and much less intensive/invasive. Most patients will experience regression as well. We try to get people in and out of colposcopy to make room for new patients.

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COLPOSCOPIC FINDINGS

“HSIL”

HPV infection and “LSIL”

Here are classic colposcopic findings of the steps in the pathway for the natural history of cervical cancer. There is a slide later with more details about what we look for and see with the colposcope but, generally as dysplasia worsens there are more and denser acetowhite areas, irregularities of the surface, and vascular changes.

Here You see a normal cervix, compared to low grade dysplasia (“LSIL”) and HPV changes. Most will regress. But in some cases of high risk oncogenic persistent HPV infection, high grade dysplasia (“HSIL) develops and can progress to cancer if untreated.

Biopsies are always done to confirm the impression and make the diagnosis.

Remember a pap smear does NOT make a diagnosis, it’s a screening test. A biopsy is required.

Reminder– LSIL : Low grade squamous intraepithelial lesion refers to low grade precancer/dysplasia

HSIL: High grade squamous intraepithelial lesion refers to high grade precancer/dysplasia

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Understanding cervical cancer prevention

Nearly all cervical cancer is caused by HPV. The HPV vaccine is highly protective against HPV infection and dysplasia/cancer.

Although most infections clear, persistent infections can cause dysplasia (abnormal pre-cancerous changes).

In colposcopy, we can detect and treat (high grade) dysplasia before it becomes invasive cancer because it normally takes years for this progression.

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Human Papilloma Virus (HPV)

Non-enveloped dsDNA virus
Transmission: Skin to skin contact, mostly sexual

Lifetime cumulative infection risk 50-80+%

> 200 genotypes, ~40 infect lower genital tract

High risk (oncogenic) HPV: HPV 16, 18, 45, 33, 31, 52, 58, 35 account for 90+ % of cervical cancers
HPV 16 = ~ 60% | HPV 18 = ~ 10-15% | HPV 45 = ~ 5%�

This Photo by Unknown Author is licensed under CC BY-SA-NC

Human papillomavirus (HPV) is a small, non-enveloped double-stranded DNA virus that infects basal epithelial cells of skin and mucous membranes.

Transmission: Primarily via sexual contact (vaginal, anal, oral)– very infectious/efficient virus (intercourse does not have to be penetrative, just genital contact can do it, condoms reduce but don’t eliminate risk). Other transmission can occur with skin-to-skin, and rarely vertical (mother → child). Fomite transmission is possible but not well studied.

HPV is a VERY COMMON virus: Lifetime cumulative infection risk without vaccination is over high 50-80 or 90%, prevalence about 40%. It’s important to normalize this for patients who have positive cervical cancer screening tests or dysplasia.

Over 200 types identified; ~40 infect the anogenital/oropharyngeal mucosa.

Classification : . Low-risk (non-oncogenic): HPV 6, 11 — cause anogenital warts (condylomata acuminata) and recurrent respiratory papillomatosis.

2. High-risk (oncogenic) that cause cancer : HPV 16, 18, 31, 33, 35, 39, 45, 51, 56, 58, 59 — cause majority of cervical, anal, vaginal, cancers, also high proportion of head/neck cancers and penile and vulvar cancers

HPV 16 and 18 are the most carcinogenic, account for ~70% of cervical cancers. �HPV Is associated with many types of cancers… most cervical and anal cancers, large proportion of Vaginal, Head and Neck, penile and vulvar cancer

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HPV Infection

Mostly asymptomatic
“Watch and wait”
Most resolve within 1-2 years

Clearance -67% 12mo, 90% 24mo
Cellular immunity
Clearance does not reliably prevent future infection (poor natural immunity)!

HPV infection reappearance: about 15% by 5 years

Reinfection or reactivation/re-detection

RISK FACTORS FOR REINFECTION

Multiple/new sexual partners
Natural (vs vaccine) immunity
Younger age

RISK FACTORS FOR PERSISTENCE

HPV type (HPV 16, 18), high viral load, coinfection with multiple types
Immunocompromised (steroids, immunosuppressants, HIV)
Smoking
Older age
Long-term oral contraceptive use

Key Teaching Point for HPV infection:

-Infection is common, asymptomatic for most. There is no antiviral treatment. (A systematic review found some interventions such as imiquimod, vaginal gels, oral supplements, photodynamic treatment, may accelerate clearance compared to natural immunity but evidence is preliminary and none is established as standard of care.)

->90% of infections clear spontaneously within 1–2 years (by the immune system); -However Even after clearing an HPV infection, reappearance of the same strain is common (can be a new infection or reactivation) Natural immunity is not good for HPV.

*Majority of HPV reactivation in middle-aged women probably reflect recurrence of previously acquired HPV

.

The overlap between persistence and redetection risk factors highlights that host immunity is the central determinant — factors that impair immune surveillance (HIV, smoking, immunosuppressive medications) promote persistence, while factors that increase re-exposure (new partners) or reflect inadequate prior immune response (low/absent seroconversion) and drive reinfection.

Extra info

Smoking: Impairs local cervical immune responses

The effect of COCs is showed in epidemiologic data, though there is some conflicting results and it is not universally accepted as causal. It appears to be promotional rather than initiating — COCs do not cause HPV infection or cervical cancer on their own, but in women already infected with high-risk HPV, the hormonal milieu may impair viral clearance and enhance oncogene expression, facilitating the transition from persistent infection to neoplasia. This is why the risk is only seen with ≥5 years of use and only in HPV-positive women, and why it is reversible after discontinuation

EXTRA INFO OCP: Showed in epidemiologic data. Proposed mechanisms: Promotion of HPV oncogene expression (E6 and E7), Promotion of HPV DNA integration, promotion of cervical ectropion exposing SCJ (primary site of HPV infection/transformation, impaired local immune clearance. CAVEAT: The association is not universally accepted as causal. A 2022 systematic review of prospective studies that controlled for pre-existing HPV infection found no consistent evidence that OC use independently increases cervical dysplasia/cancer risk, noting that methodological limitations (failure to distinguish COC from progestin-only pills, reliance on self-reported use) cloud interpretation. Confounding by sexual behavior (COC users tend to have more partners, less barrier contraceptive use) and detection bias (more frequent Pap screening among COC users) remain difficult to fully exclude

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PRIMARY PREVENTION IS POSSIBLE!! �

Gardasil 9 protects against

High risk oncogenic HPV : HPV 16, 18, 45, 33, 31, 52, 58 (accounts for 90% of cervical cancers)

Low risk non oncogenic HPV: HPV 6 and 11 (accounts for 90% anogenital warts)

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Vaccine efficacy: Cervical cancer/dysplasia

Age Group	Per-Protocol Efficacy (HPV-naïve)	ITT Efficacy (all women)	Why the Difference?
9–14 years	Antibody titers higher than 15–26 yr group (2 doses sufficient)	Not tested (pre-sexual debut)	Almost no prior HPV exposure
15–26 years	96–100% (CIN2+, HPV 16/18)	45–65%	~25–45% already HPV-exposed
24–45 years	84.7%	41.6%	Majority already HPV-exposed

2. REAL WORLD DATA: Effects of HPV Vaccination Programs on Community Rates of HPV-Related Disease and Harms. Cochrane Database Syst Rev. Nov 2025

OpenEvidence Summary

1. RCT Evidence

🎯 BOTTOM LINE

HPV vaccination probably reduces cervical cancer by ~80% (if vaccinated ≤16 yrs), with consistent reductions in pre-cancer and genital warts
No serious safety signals were identified across 132 million people
Evidence for rarer HPV-related cancers remains limited

It works very well! Efficacy was 96-100% in the RCTs for 9-26 year olds that were HPV naïve (never exposed to HPV, documented HPV negative at the start of tria)l- the “Per protocol group)) * This is the best population to vaccinate.

There is decreased efficacy as women age or are exposed to HPV (i.e. in the ITT-intention to treat group that includes those that were sexually active, had had HPV or dysplasia or abnormal pap).

How well does the vaccine work out of trial conditions, in the real world? There are many database and epidemiologic cohort studies and a Cochrane review to answer this. The Conclusion is that it certainly reduces HPV infection and precancer and warts, and therefore probably cervical cancer too … and is safe. It works best when we vaccinate younger people, not surprising.

(Why “probably reduces cervical cancer”? Most data reports infection or HSIL reduction. Cervical cancer prevention data takes longer to accumulate since it takes time to develop cervical cancer, more common as people get older and the vaccine trials are still relatively new).

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HPV Vaccination

Gardasil 9 approval in Canada is for 9-45 years old (male/female)

Type-specific humoral antibody production to prevent NEW infections
Side Effects: injection site pain / erythema / swelling

Interrupted series do NOT require restart
Not recommended in pregnancy

No harm to mom/fetus reported, but not well studied

OK during breastfeeding

No recommendation for Nanovalent vaccine after completing previous version of HPV vaccine (bivalent/quadrivalent)

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Reimbursement varies by province: In Alberta: 9-26 yo, 2 doses (Grade 6 school program)

Target Group	Recommended Dosing	Minimum Intervals
9 - 20 yo	1 dose	-
21 – 26 yo	2 doses	24 weeks apart
27 + *(shared decision making)	2 doses	24 weeks apart
Immunocompromised or living with HIV	3 doses	Dose 1 to 2: ≥ 4 weeks�Dose 2 to 3: ≥ 12 weeks�Dose 1 to 3: ≥ 24 weeks

National Advisory Committee on Immunization (NACI) Guidance

(Updated 2024) on HPV vaccination

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Prescribe the vaccine

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Understanding cervical cancer prevention

Nearly all cervical cancer is caused by HPV. The HPV vaccine is highly protective against HPV infection (and dysplasia/cancer).

Although most infections clear, persistent infections can cause dysplasia (abnormal pre-cancerous changes).

In colposcopy, we can detect and treat (high grade) dysplasia before it becomes invasive cancer because it normally takes years for this progression.

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HPV persistence: Dysplasia

Remember that most HPV infections clear (90% by 2 years)
Only 3-5% of persistent HPV infections result in dysplasia/cancer

Persistence with high risk HPV is necessary for dysplasia

Progression to HSIL occurs almost exclusively with persistent high risk HPV;
Transient/negative infections do not progress, no HSIL
Genotype matters: HPV 16: 55%, HPV 33/18/31: ~31–33%, HPV 56: 3% of HSIL

Mechanism: Viral integration into host DNA🡪 Sustained E6/E7 oncoprotein expression 🡪 Checkpoints lost in cell cycle regulation resulting in loss of apoptosis and increased proliferation 🡪 Clonal transformation and expansion of abnormal cell 🡪 DYSPLASIA 🡪CANCER

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Understanding cervical cancer prevention

Nearly all cervical cancer is caused by HPV. The HPV vaccine is highly protective against HPV infection (and dysplasia/cancer).

Although most infections clear, persistent infections can cause dysplasia (abnormal pre-cancerous changes).

In colposcopy, we can detect and treat (high grade) dysplasia before it becomes invasive cancer because it normally takes years for this progression.

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CERVICAL CANCER SCREENING

HPV testing Pap smears

Detect high risk and persistent HPV infection
Screen for cervical dysplasia

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HPV Testing

Pap Smears

THOSE AT RISK:

COLPOSCOPY WITH BIOPSIES

TO CONFIRM HSIL

So Paps and HPV testing are done within the screening program to identify those at risk of and having hjigh grade dysplasia and small cancers.

Patients found to be at risk of dysplasia and cancer are referred to colposcopy for exam and biopsies. Biopsies confirm the diagnosis.

Note that HPV testing can be done on a pap test (ie in Alberta) or another swab collected by a provider or even a self-swab by patient (Alberta does not have the self swab option available yet, but hopes to have this in the future).

IMPORTANT POINT WHEN DISCUSSING RESULTS WITH PATIENTS: Paps and HPV test results DO NOT make or confirm a diagnosis of cancer or precancer.

These are screening tests. (for example high grade dysplasia can be found in a patient presenting with a low grade or ASCUS pap; converselyh there may only be dysplasia when a pap result is cancer and vice versa).

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HPV TESTING IS BETTER

Canadian Cervical Cancer Screening Trial (CCCast)

Prospective cohort study, HPV testing vs conventional cytology in women aged 30-69yo
Accuracy for CIN 2+ (HSIL) and worse pathology

*ALBERTA: Transition to HPV primary testing is in phases

(currently for those 50+, 40-50 coming? Fall 2026)

	Sensitivity	Specificity
HPV Testing	94.6%	94.1%
Cytology	55.4%	96.8%

COMBINED TRIAGE (HPV with PAPs) IS BEST

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Order a pap smear or HPV Screen

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Risk of HSIL (≥5%) 🡪 Colposcopy

Cytology	HPV negative	HPV unknown	HPV positive	HPV16 positive
NILM	~0.3%	<1%	3.4%	5.3%
ASC-US	~0.3%	~3%	4.4%	9–12.9%
LSIL	~1.4%	~3-5%	4.3%	11%
ASC-H	~3.5%	~25%	26%	28%
HSIL	~25%	~50%	49%	60%

Estimates summarized by AI based on 2019 ASCCP guidelines, 2023 Canadian guidelines

HSIL risk increases with HPV and high grade cytology

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Who is referred to colpo?� HPV Primary Screening (>50)

Immediate referral

High probability of high grade dysplasia/cancer

Repeat testing to document persistence or progression

Low grade cytology (ASCUS, LSIL) or normal with high risk HPV “other” infections (not 16/18)

HPV screen	Cytology
HPV 16	Carcinoma
HPV 18	AGC/AIS
Any HR HPV, immunocompromised	HSIL
	ASC-H

See guidelines for details and special cases!

Current Alberta Guidelines 2026

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Who is referred to colpo?� Pap smear screening (25-49)

Immediate referral

High grade cytology: Carcinoma, AGC/AIS, HSIL, ASC-H
Low grade cytology with reflex HPV testing +
Concerning exam regardless of Pap smear result

Repeat testing (document persistence/progression)

Low grade pap smear (ASCUS, LSIL)

See guidelines for details and special cases!

Current Alberta Guidelines 2026

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https://www.sciencedirect.com/science/article/pii/S0208521622000122

Created with Chat GPT

COLPOSCOPIC ASSESSMENT

In colposcopy, Acetic Acid and Lugol’s iodine are used along with magnification of the cervix to identify abnormal areas and rule in or exclude dysplasia and cancer with biopsies

(There are more and denser white areas, more irregularities of the surface, more vascular changes with HSIL (CIN2 < 3) and most with cancer

The Reid colposcopic index (RCI) can be used as a guide.

Targeted biopsies are done to confirm the impression and document or exclude high grade dysplasia.

Reminded - It is NOT used to surveil/monitor or screen for progression from HPV infection to high grade precancer. Paps and HPV test do that well and are cheaper, and much less intensive/invasive. Most patients will experience regression and so we try to get people in and out of colposcopy to make room for new patients.

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TREATMENT: EXCISION OR ABLATION

Ablation with laser or cryotherapy is acceptable for HSIL, not invasive cancer

LEEP

(Alternative: Cone)

CO2 Laser Ablation

(Alternative: Cryotherapy)

In Select Cases:

HYSTERECTOMY OR TRACHELECTOMY

Once find HSIL, You treat this high grade dysplasia by either ablating it with CO2 laser or cryotherapy (not done here), or excising it.

Excision of the transformation zone and lesion can be be done in the ambulatory setting by LEEP (loop electrosurgical excision procedure) with local anesthetic injection to the cervix; or a cold knife conization that requires general anesthesia.

In select cases you may to proceed with removal of the entire cervix (either with Trachelectomy, or more commonly along with the uterus with a total hysterectomy)

Excisional treatment has the benefit of pathologic confirmation of the HSIL, and can effectively treat a small cancer. You never ablate if there is risk of invasive cancer. We treat most HSIL by LEEP.

With excision of ablation, you get rid of the cells that would have become cancer. It also helps with HPV clearance.

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After the treatment of HSIL

Long term cancer risk is 5x general population
Residual/recurrence risk for HSIL is 5-17%, most within 2 years

Recurrence risk driven by persistent high risk HPV infection (more than margin status)

SOLUTION:

Surveillance in colposcopy until HPV test of cure is negative
Long term screening (“for life”), more frequent screening

Yearly Pap smears (25-49), HPV primary screen q3 years

Long term cancer risk is 5x general population after HSIL treatment.

There is a risk of residual or recurrent HSIL of about 15%. More recurrence with with positive margins on the LEEP.

A LEEP removes the visible lesion and the transformation zone of the cervix, but it does not necessarily eradicate the underlying HPV infection—and persistent high-risk HPV is what drives recurrence risk the most.

Knowing this, we can reduce the risk of undetected dysplasia and cancer with close surveillance.

Patients who have had a leep have HPV testing in follow-up. They remain in colpo if HPV positive and are only discharged back to community screening when HPV negative because the risk of HSIL drops significantly.

However we recommend long term (at least 25 years, better for life) screening, and more frequently than routine to detect HPV reactivation and dysplasia.

In Alberta, this means yearly pap smears for those aged 49 and under (rather than q3 yrs) and q3 yearly primary HPV testing rather than q5yearly. Although the screening is more frequent, the referral guidelines are the same for colpo.

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Understanding cervical cancer prevention

Nearly all cervical cancer is caused by HPV. The HPV vaccine is highly protective against HPV infection (and dysplasia/cancer).

Although most infections clear, persistent infections can cause dysplasia (abnormal pre-cancerous changes).

In colposcopy, we can detect and treat (high grade) dysplasia before it becomes invasive cancer because it normally takes years for this progression.

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NEXT STEP: CERVICAL CANCER ELIMINATION

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Authors

Jeanelle Sabourin, Gynecologic Oncologist

Based on slides by Preety Nijar, Bruno Svajger, Ameeta Singh, Christa Aubrey

Summaries and slides by OpenEvidence/Chat GPT AI

Created August 2026