WEEK 2: HPV AND CERVICAL CANCER WORKSHOP

Question 1

What is the major cause of infection-related cancer in both men and women?

Name all cancers caused by HPV.

Answer 1

Human Papillomavirus (HPV) is
Major cause of infection-related cancer in both men and women

Responsible of 4.5% (630,000) of all new cancer cases worldwide

Responsible for virtually all cervical cancer and a fraction of cancers of the vulva, vagina, penis, anus, and head and neck cancers

Cause of anogenital warts and recurrent respiratory papillomatosis

Increasing trends in HPV-related anal and head and neck cancers have been observed in the last decade.

Question 2

What is the fourth (4th) most frequent cancer among women and the fourth leading cause of cancer deaths worldwide?

Describe the distribution of HPV according to economy.

Answer 2

HPV-related cancer remains a leading cause of morbidity-mortality in many parts of the world, particularly in less developed countries.

Diagnosed in more than 90% of cervical cancers.

Cervical cancer is the fourth (4th) most frequent cancer among women and the fourth leading cause of cancer deaths worldwide.

Overall, the HPV repartition data show that HPV infection and related diseases are more prevalent in developing countries.

Question 3

What is the % by which the Universal HPV vaccination could prevent HPV-related cancers?

Answer 3

Universal HPV vaccination could prevent between 70% and 90% of HPV-related.

Question 4

Cancer is a major public health problem worldwide.

It is one of the most leading causes of death in several regions depending upon disparities among different people.
Outline these disparities.

Answer 4

-Socioeconomic
-Ethnic, racial and cultural factors that differ between low and high-income countries
-Level of education

Question 5

What causes vast majority of cervical cancers?

How is HPV transmitted?

Answer 5

Cervical cancer is an abnormal growth in the lower, narrow part of the womb—known as the cervix.

Almost all cervical cancers are caused by virus—known as human papilloma virus (HPV). HPV 16 is consistently the most frequent genotype in all cancer related genotypes.

HPV is a common virus that is passed from one person to another through sexual intercourse.
Usually, the body fights off the HPV infection—however, over time there are few instances whereby it evolves into cancer.

Question 6

Outline other risk factors for cervical cancer.

Answer 6

Other risk factors include:
Smoking
Immunosuppression, e.g. HIV infection
Unhealthy diet (low in fruits/vegetables)
Long term oral contraceptives use.
Multiple full-term pregnancies
Multiple partners

Question 7

What is the leading cancer in both males and females in Botswana?

Answer 7

Kaposi sarcoma

Question 8

State the 5 main most common female cancer in Botswana.

Answer 8

Kaposi sarcoma
Cervical cancer
Breast cancer
Non-Hodgkins Lymphoma
Corpus uteri cancer

Question 9

Why are Genital HPV infections very common?

Which HPV can lead to cancer?

What percentage of cervical cancer is caused by high risk HPV?

Describe the natural history of HPV infection.

Answer 9

-Very common
-HPV very contagious
-Skin –to-skin transmission
-Begin to occur soon after sexual debut

Only high-risk HPV types lead to cancer.
About 12 high-risk HPV types are responsible for essentially all cervical cancers, including HPV types 16 and 18, which together cause about 70 percent of cervical cancers.

Natural history
90% clear within 2 years
~10% persist.

Question 10

In what years does the prevalence of cervical HPV reduces sharply in women?

Answer 10

The prevalence of cervical HPV reduces sharply in women more than 30 yrs.

Question 11

What is Botswana’s HIV prevalence in ages 15–49?

Answer 11

Botswana’s HIV prevalence = 24.8% (ages 15–49)

Question 12

What is the likely prognosis for HIV-infected women (vs. HIV-uninfected) more likely to have.

Answer 12

Persistent HPV infections
Multiple HPV infections
Higher burden of cervical pre-cancer and cancer
Earlier appearance of cervical cancer

Question 13

Describe the Prevention approaches for HPV and cervical cancer.

Answer 13

1. Primary prevention: Manage risk factors and prevent onset of disease.
2. Secondary prevention: Early detection and treatment.
3. Tertiary prevention: Prevent complications and disability.

Question 14

Describe the Natural history of cervical cancer.

Answer 14

Exposure to HPV infection early in adolescent life
Progression to cervical pre-cancer stage
Development of invasive cancer cells

Question 15

What stage is extremely important for prevention and control of cervical cancer?

Describe the Botswana’s approach to cervical cancer.

Answer 15

Luckily between HPV infection and the development of invasive cervical cancer, there is a critical stage known as pre-cancer stage. This stage is extremely important for prevention and control of cervical cancer.

Intervention at this stage is a life saver. For comprehensive cervical cancer prevention and control, WHO recommends a three-pronged approach:

1) Primary prevention through HPV vaccination and health information and education to reduce high-risk sexual behavior to limit HPV transmission/acquisition.

2) Secondary prevention consisting of screening and treating for the presence of precancerous lesions and early diagnosis and treatment of early cancer while the chance of cure is still good;

3) Tertiary prevention when the cancer is at an invasive stage, dealing with Treatment and Palliative care.

The 3 components need to be implemented within the context of countries’ health systems, benefitting from and contributing to the different health systems components such as human resources, information systems, etc.

Question 16

At what age does pre-cancers usually visible?

Answer 16

30 yrs +

Question 17

Cervical cancer is almost 100% preventable – but must detect and treat precancerous lesions.

What is primary and secondary prevention?

Answer 17

Primary Prevention
-Prevent HPV infection from occurring in the first place.

Secondary Prevention
-Detect and treat precancerous lesions.

.

Question 18

State the primary prevention methods of cervical cancer.

Answer 18

-Abstinence, delayed sexual activity
-Condoms
-Healthy living (e.g., not smoking)
-Vaccine in girls and boys from ages 9-13.
-Safe male circumcision

Question 19

Outline 2 methods which should be most focused on in primary prevention of cervical cancer.

Answer 19

-Prevention must therefore focus on changing sexual practices and other behaviors that increase risk of infection.

-Risk reduction counseling should be incorporated at all levels of health care system.

Question 20

Secondary prevention of Cervical cancer involves screening.

Describe the principles of screening.

Answer 20

-Screening test must be effective at identifying women with easily treatable precancerous lesions.

-Health care workers must be able to treat these precancerous lesions safely and effectively.

-Must link screening with treatment.

-Must be feasible and acceptable in local setting.

Question 21

What is the need for screening?

Answer 21

-No signs or symptoms at precancerous (easily treatable) stage.
-Signs and symptoms only occur at late stage of cancer.

Question 22

What was the first screening method for cervical cancer in Botswana?

Answer 22

Visual inspection with acetic acid (VIA):

-An evidence-based alternative approach
-Safe, effective, feasible, highly acceptable, and sustainable in low-resource settings
-Promotes linkage of screening with treatment

Question 23

Describe the WHO guidelines for screening and treatment of precancerous lesions for cervical cancer prevention: 2013.

Answer 23

“Use a strategy of screen with VIA and treat, over a strategy of screen with cytology followed by colposcopy (with or without biopsy) and treat.”

Question 24

How does Visual inspection with Acetic acid work?

Answer 24

*Thoroughly soak the cervix with dilute 3-5% acetic acid solution (white vinegar) – ensure the strength of acetic acid.

*Wait at least 1 minute after removing acetic acid-soaked swab from cervix – visualize cervix with an unaided eye.

*Abnormal tissue appears white (acetowhite).

*Acetowhite changes that appear quickly and recede quickly – more likely squamous metaplasia or inflammation

*Acetowhite changes that last longer than 1 minute after removing acetic acid are more likely precancerous

Question 25

What does acetowhite changes that appear quickly and recede quickly – more likely to be?

What is acetowhite changes that last longer than 1 minute after removing acetic acid are more likely to be?

Answer 25

*Acetowhite changes that appear quickly and recede quickly – more likely squamous metaplasia or inflammation.

*Acetowhite changes that last longer than 1 minute after removing acetic acid are more likely precancerous.

Question 26

What are the principles emphasized when screening using VIA?

Answer 26

We will return to these principles, but emphasize the need:

-For appropriate strength acetic acid (3-5%, leaning more towards 5%) – white table vinegar
-A bright white light source
-Waiting at least one minute – if no lesion at one minute, wait an additional 15 – 30 seconds to be sure.

Question 27

Describe the pathophysiological basis of VIA.

Answer 27

*Normal epithelium -> little protein, little coagulation -> light is able to pass through the epithelium -> cervix continues to look pink.

*Abnormal epithelium (CIN) -> high levels of protein, much coagulation -> prevents light from passing through the epithelium -> Aceto whitening. occurs

Question 28

What is VIA positive cases?
Describe examples of VIA-Positive.

Answer 28

VIA-positive cases (precancerous lesions) consist of thick, dense, opaque acetowhite lesions confined to the transformation zone, near to and often touching the SCJ. (Squamous cell junction).

Therefore, it is essential that the SCJ and transformation zone are seen in their entirety.

The acetowhite changes associated with CIN and early cervical cancer are more dense, thick, and opaque with well demarcated margins from the surrounding normal epithelium (as if you can draw a line around the lesion).

Question 29

Describe the acetowhite changes associated with immature squamous epithelium and inflammation?

Answer 29

In contrast to CIN, the acetowhite changes associated with immature squamous epithelium and inflammation are pale, thin, often translucent, and patchy with ill- defined margins.

Question 30

Differentiate between acetowhite changes due to CIN and those due to immature squamous cell metaplasia and inflammation in relation to time?

Answer 30

Acetowhite changes due to CIN and early cervical cancer reverse much more slowly than immature squamous metaplasia and inflammation, with changes that may last 3-5 minutes following application of acetic acid, especially with more severe lesions.

In contrast, acetowhite changes associated with immature squamous epithelium and inflammation tend to appear quickly, but also may quickly disappear, often within a minute.

This underscores the importance of visualizing the cervix the entire time following application of acetic acid and waiting at least one full minute by the clock before making a determination of the VIA reading.

Question 31

What is the effectiveness of VIA in comparison to Pap smear?

Answer 31

While some people still hold onto the belief that Pap smears are technically superior to VIA, the evidence suggests otherwise, as illustrated in this table.

VIA is comparable to, or even better than, Pap smears in detecting precancerous lesions of the cervix.

HPV testing, if available, is recommended above Pap smear or VIA. But cost and logistical issues make it not feasible in many settings.

Question 32

State the HPV Collection / Testing commodities.

State the 14 HR HPV types tested.

Answer 32

*Self-collection by women
1022 women in 5 sites
Samples transported in preservCyt to central lab.
Results released either in 2 hours or within 3 days.
(3 weeks).

Tests for 14 oncogenic HPV types
-Small lab footprint
-1-4 specimens per run
-1 hour run time.
-$10-11/test

14 HR HPV Types tested: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68,

Question 33

What to do with VIA-positive cases?

Even if you have a perfect screening test, if you do not link it with treatment, it is not effective, and in fact is harmful.

What screening method promotes linkage of screening and treatment?

Answer 33

For a program to be effective, screening must be linked with treatment.

VIA promotes that linkage.

Question 34

State the 5 Criterions for Choice of Treatment.

Answer 34

Effectiveness
Safety
Cost
Convenience
Training – “Learning Curve”

Question 35

What is cryotherapy?

What are some of the ways it can be administered?

What is usually used for?

Answer 35

Cryotherapy is a medical procedure that involves the use of cold temperatures to treat various medical conditions, particularly skin lesions, and is sometimes referred to as “cold therapy.”

It can be administered in several ways, including the application of cold gases, liquids, or probes to freeze and remove abnormal or unwanted tissue.

Cryotherapy is commonly used to treat skin conditions, but it can also be applied to certain internal tissues or organs.

Question 36

How does freezing process in cryotherapy destroy cervical precancerous tissue?

Answer 36

Freezing process that destroys cervical precancerous tissue by:

-Direct cell injury
-Vascular stasis

Question 37

Describe the process of cryotherapy.

Answer 37

*Apply cryotip to cervix and freeze for 3 minutes
*Defrost for 5 minutes
*Re-freeze for 3 minutes
*Review post-treatment and follow-up instructions
*Document findings and treatment

Question 38

What is the relation between freezing rate and cell death?

Compare the minimum temperature required for cell death and vascular stasis?

Why is it necessary for freezing for 3 minutes?

Why is it important not to “over-defrost” during the active defrost, that is, do not keep the cryotip on the cervix after it has turned “gold”?

Answer 38

Note the following:
-Faster freezing rates result in more cell death.

Increasing the hold time at the minimum temperature increases cell death rate. This is where the 3-minute freeze is important.

-Slower thaw rate increases the destructive effects of cryotherapy.

This is where it is important not to “over-defrost” during the active defrost, that is, do not keep the cryotip on the cervix after it has turned “gold” as you will be warming the cervix back up and preventing the precancerous tissue from being destroyed.

Question 39

How is freezing accomplished in cryotherapy?

Answer 39

Ablative therapy for cervical lesions
Freezing accomplished through special probes using carbon dioxide or nitrous oxide gas

Question 40

State the Eligibility Criteria for Cryotherapy.

Answer 40

-Lesion not suspicious for cancer
-Can see the entire extent of the lesion; lesion does not extend into the endocervical canal
-Lesion occupies <75% of the cervix
-Cryotip covers the lesion
-No anatomical deformity of the cervix that prevents good application of cryotip
-Client is not pregnant
-Client is more than 6 weeks postpartum
-Client does not have severe cervicitis

Question 41

What is the % effectiveness of cryotherapy

Answer 41

Effectiveness
-Cure rates: >90% when using strict eligibility criteria (size, e.g., cryotip can cover entire lesion)

Question 42

Most lesions (85–90%) are eligible for cryotherapy (less in HIV+ women).

Why is it less HIV+ Women?

Answer 42

HIV-infected women tend to have larger lesions, often twice the rate (or even more) than their HIV-negative counterparts.

Question 43

What is the chance of infection after cryotherapy?

Answer 43

<1% infection (usually local)

*Does not affect future fertility or future pregnancies
*Not used during pregnancy

Question 44

What is the most common and bothersome side-effect of cryotherapy?

Why does it happen?

Answer 44

Side effects: cramping; watery discharge for 4–6 weeks.

The watery discharge, which can be heavy. This should be explained to the woman as normal, her cervix shedding the “bad cells” and healing itself.

Question 45

One of the considerations for cryotherapy is due to task shifting and flexibility in mobility of the service providing areas.

Who can perform a cryotherapy?

Where can cryotherapy be provided?

Answer 45

Task Shifting
Nurses, midwives and doctors all able to competently perform cryotherapy.

Mobile
Can safely provide cryotherapy in stationary or mobile clinics.
Does not require source of electricity.

Question 46

Cost is one of the reasons that cryotherapy is considered.

Between the Co2 and Nitrogen which one is less expensive?

Answer 46

Costs
Gas: CO2 is usually less expensive than N2O:
Costs and availability vary by local conditions.

Question 47

What is the general trend for Average VIA+ rates and Cryotherapy eligibility in HIV positive women?

Answer 47

HIV+ women not only tend to have higher VIA+ rates, but also larger lesions, with a greater percentage not eligible for cryotherapy.

All of these data should be used to monitor the quality of the program (more during M&E sessions), but also to forecast materials and supplies based on the rates of screening, VIA-positivity, and eligibility for cryotherapy.

*Average VIA+ rate: 5–10% (higher among HIV+ women)
*Cryotherapy eligible: 85–90% (lower among HIV+ women)

Question 48

What is thermal ablation?

Answer 48

An ablative treatment of CIN.

Thermal ablation in the context of cervical cancer is a medical procedure that uses heat to destroy or remove abnormal cervical tissue, particularly precancerous or early-stage cancerous lesions.

It is a treatment option that aims to eliminate or reduce the cancerous tissue while preserving the surrounding healthy tissue.

Question 49

What are the general considerations about thermal ablation?

Answer 49

-It is an ablative treatment
-Effective to treat CIN 2-3
-Task shifting: MD and nurses
-Can perform biopsies before treatment (if needed)
-Power source: direct electrical (desktop) vs. battery (handheld)

Electrical: desktop, variety of tips/thermo-probes
Battery/dual source: portability; reportedly lasts for 20 treatments/day.

Question 50

What are the eligibility Criteria for Thermal Ablation?

Answer 50

-VIA/DC positive; hrHPV positive followed by VIA/DC
-Lesion not suspicious for cancer
-Can see the entire extent of the lesion; lesion does not extend into the endocervical canal.
-Lesion occupies less than 75% of the cervix
-No polyps or anatomical deformity of the cervix that prevents good application of thermo-probe tip
-Client is not pregnant
-Client is more than 6 weeks postpartum.
-Client does not have severe cervicitis.

Question 51

Describe the procedure for performing thermal ablation.

Answer 51

*Outpatient – clinic/mobile clinic

*Confirm not pregnant

*Obtain informed consent

*No anesthesia required

*Perform visual inspection (VIA): confirm presence, size, location of lesion (eligibility for thermal ablation).

*Apply heated probe (100°C) to cervix to cover lesion and transformation zone

*Treat for 45-60 seconds (minimum of 30s))

*Review post-treatment instructions and follow-up

Question 52

What does LEEP stand for?

What is LEEP?

Answer 52

*Loop Electrosurgical Excision Procedure

*Outpatient procedure that uses a thin wire loop heated with electricity to excise the abnormal tissue of the cervix.

Question 53

When Should the Woman Be Referred for LEEP?

Answer 53

*Lesion present but too large to be treated with cryotherapy.

*Lesion present and extends into the cervical canal.

*Lesion suspicious for cancer (biopsy for diagnosis only – LEEP is NOT a treatment for cancer).

*HSIL on pap smear

HSIL stands for High-Grade Squamous Intraepithelial Lesion.

*10–15% of VIA+ women will not be eligible for cryotherapy (higher in HIV+ women).

Question 54

What are the 3 advantages of LEEP?

Answer 54

Advantages
Cure rates: 90 – 95%
Can treat large lesions/endocervical extension
Histopathology

Question 55

State the 4 diasadvantages of LEEP.

Answer 55

Disadvantages
-Cost
-Local anesthesia
-Training
-Slightly higher risks

Question 56

Outline the LEEP Steps.

Answer 56

*Provide counseling.
*Do speculum exam to see cervix.
*Perform VIA/Colposcopy.
*Inspect cervix for acetowhite lesions and extent of lesions.
*Discuss results with the woman; offer treatment option if positive and meets eligibility criteria.
*Injection of anesthesia on the borders of the lesion
*The starting point for excision is 5 mm outside the outer boundary of the lesion.

Orient the loop perpendicular to the surface of the ectocervix above the starting point.

When the loop is ready just above the starting point, but not touching the tissue, activate the current by depressing the cutting button or foot pedal.

Introduce the loop into the tissue, letting the loop cut its path, and not pushing it in.

Provide directional guidance until a depth of at least 5 mm is reached (a crossbar can be a helpful guide, especially for beginners).

Once the appropriate depth is reached, gradually guide the loop parallel to the surface of the ectocervix until it reaches a point 5 mm outside the opposite outer boundary of the lesion.

Then withdraw the loop, keeping it perpendicular to the surface of the ectocervix.

Stop the current (let go of button or foot pedal) as soon as the loop exits the cervix.

Question 57

Compare cryotherapy and LEEP.

Answer 57

CRYOTHERAPY
*Uses CO2 or N2O
*Effective for small lesions
*No anesthesia needed
*Cheaper cost
*Can be provided by nurse or physician
*No tissue is obtained
*Higher acceptability by patient
*Minor side effects: 1-3%

LEEP
*Uses electrosurgical unit and power.
*Effective for all lesions
*Anesthesia needed
*Costly compared to Cryotherapy
*Administered by trained physician only
*Tissue is obtained and can be used for histology
*Higher acceptability by patients
*Minor side effects: 1-5%

Question 58

What is the effectiveness % for the following?
*Cryotherapy
*LEEP
*Thermal ablation

Arrange them in order of lowest to highest cost.

Answer 58

*Cryotherapy: 85-95%
*LEEP: 90-95%
*Thermal ablation: 90-95%

Thermal ablation, Cryotherapy, LEEP.

Question 59

Describe the new strategy secondary prevention algorithm.

Answer 59

SCREENING METHOD
1. Pap smear (cytology)
2. Visual inspection with acetic acid (VIA)

DIAGNOSIS
1. Colposcopy and biopsy

TREATMENT
1.
-Cold knife conization (hospital/gen anesthesia) or
LEEP.
2.LEEP or cryotherapy.

NOTE: HISTOLOGY is always before treatment using LEEP.

Question 60

What is the future strategy for Cervical cancer prevention planned to include?

Answer 60

HPV DNA testing

Question 61

What are the two ways cervical cancer prevention can be made more effective?

Answer 61

1. To be most effective, these services should be part of a comprehensive strategy and be linked to other women’s health services.

For example, family planning or HIV care and treatment clinics

2. Task-shifting and district-based implementation of interventions help bring VIA/cryotherapy close to where people live.

Nurse or midwife who works in the community is often the best person to provide community-based, appropriate, safe, and cost-effective care.

Question 62

Describe the prophylactic HPV vaccines.

Answer 62

-Created in the laboratory.
-Virus-like particle
-Not infectious
-Creates immunity to HPV certain types

Question 63

State the function of the following HPV vaccines.

1. Cervarix® (bivalent)
2. Gardasil®/Silgard® (quadrivalent):

Answer 63

Cervarix® (bivalent):
Prevents precancerous lesions
and cancers from HPV types
16 and 18.

Gardasil®/Silgard® (quadrivalent):
Prevents precancerous lesions,
cancer, and anogenital warts from
four HPV types 6, 11, 16 and 18.

Both are prophylactic– work best in individuals naïve to the vaccine types.

Question 64

How are vaccines administered?

Answer 64

Both require 2 or 3 doses administered over 6 months (Refer to SAGE recommendations)

Need for booster doses not established.

Still monitoring but very effective and likely long-lasting protection.

Question 65

Large efficacy trials conducted in females ~16-26 yrs.

What is the % efficacy against cervical precancers due to vaccine types among females for both vaccines?

What is the % efficacy against genital warts for quadrivalent vaccine?

Can the vaccines provide therapy to those already having cervical cancer?

Answer 65

High efficacy against cervical precancers due to vaccine types among females for both vaccines (>90%)

High efficacy against genital warts for quadrivalent vaccine (>98%)

Vaccines not therapeutic; no evidence of efficacy against progression to disease if infected at time of vaccination

Question 66

What are the WHO recommends including HPV vaccine in national immunization programs where:

Answer 66

Cervical cancer prevention is a public health priority.

Introduction is feasible and financially sustainable.

Cost-effectiveness has been considered.

Prioritize target population of girls 9-10 through 13 years.

Question 67

Outline challenges: Costs of HPV vaccine introduction in low resource setting.

Answer 67

Vaccine costs remain significant.

Vaccine delivery costs.

Question 68

State challenges: Unique to HPV vaccine introduction in adolescent groups.

Answer 68

Adolescent age group
-Immunization programs mainly focus on infants and children.
-Introduction of HPV vaccines in developing countries could assist in establishing preventive care for adolescents.
-School based vaccination successful in some setting but more costly and does not reach out of schoolgirls

Question 69

What New stakeholders and partners are needed in the administration of HPV vaccine in adolescent groups?

Answer 69

Immunization, reproductive health, adolescent health, school health, cancer control, and HIV prevention partners
Interdisciplinary coordination needed.