The document discusses cervical cancer screening guidelines and strategies, comparing the use of Pap tests, HPV tests, and primary HPV screening. It provides information on the epidemiology of HPV and progression to cervical cancer, as well as data from studies showing that primary HPV screening can detect more high-grade cervical lesions than cytology alone.
HPV Diseases More Than Cervical Cancer, Dr. Sharda Jain Lifecare Centre
HPV Disease . Cervical cancer , prevention cervical cancer , HPV prevention , cancer prevention , Human Papillomavirus (HPV), cervical cancer prevention
Using Mobile Phones for Cervical Cancer ScreeningClickMedix
ClickMedix founder partnered with University of Pennsylvania and Botswana-UPenn Partnership program to pioneer cervical cancer screening using mobile camera phones.
*Note: This presentation contains medical images which may be unsuitable for those not accustomed.
HPV Diseases More Than Cervical Cancer, Dr. Sharda Jain Lifecare Centre
HPV Disease . Cervical cancer , prevention cervical cancer , HPV prevention , cancer prevention , Human Papillomavirus (HPV), cervical cancer prevention
Using Mobile Phones for Cervical Cancer ScreeningClickMedix
ClickMedix founder partnered with University of Pennsylvania and Botswana-UPenn Partnership program to pioneer cervical cancer screening using mobile camera phones.
*Note: This presentation contains medical images which may be unsuitable for those not accustomed.
Cancer Biomarkers Research, HPV and Cancer, HPV VaccineJames Lyons-Weiler
An overview of advances in cancer biomarker research strategies, the pathogenesis of HPV virus and a focus on the HPV vaccine with an analysis of evidence of type replacement.
HPV Infection , HPV Vaccination , Cervical cancer , Cancer in India , Dr. SHA...Lifecare Centre
HPV inefection , HPV disease prevention, Cervical cancer prevention , Cervical cancer treatment, Female cancer , Female cancer prevention , Uterine cancer , Cancer in india
Treatment Deintensification in HPV positive head and neck cancerDr Rushi Panchal
This ppt is providing detail of current status and future direction of treatment deintensification strategies of head and neck cancer in era of HPV positive sq cell carcinoma.
HPV Testing is essential in the triage of ASC-US and/or LSIL cytology. The test helps to clearify the situation after treatment of high-grade CIN and to resolve uncertainties after diagnostic and or consecutive treatment. 2016 up to date information is give by the presentation.
Primary HPV testing or co-testin
Anal dysplasia: Diagnosis and Management, OR Everything you ever wanted to kn...CBRC
Screening, treatment and prevention of Anal
Intraepithelial Neoplasia (AIN) Presented by Joel Palefsky, UCSF School of Medicine, San Francisco at the 5th Annual Gay Men's Health Summit held in Vancouver, BC on November 9th and 10th, 2009.
The Natural History of Type-specific Human Papillomavirus Infections in Femal...Alberto Cuadrado
Little is known about the average duration of typespecific
human papillomavirus (HPV) infections and their
patterns of persistence. The objectives of this study were
to evaluate the rate of acquisition and clearance of
specific HPV types in young women. Female university
students (n 621) in Montreal were followed for 24
months at 6-month intervals. At each visit, a cervical
specimen was collected. HPV DNA was detected using the
MY09/MY11 PCR protocol followed by typing for 27
HPV genotypes by a line blot assay. The Kaplan-Meier
technique was used to estimate the cumulative probability
of acquiring or clearing a HPV infection considering
types individually or in high-risk (HR) or low-risk (LR)
groups defined by oncogenic potential. Incidence rates
were 14.0 cases/1000 women-months (95% confidence
interval, 11.4 –16.3) and 12.4 cases/1000 women-months
(95% confidence interval, 10.4 –14.8) for acquiring HR
and LR HPV infections, respectively. The 24-month
cumulative rates of acquisition were highest for HPV-16
(12%), HPV-51, and HPV-84 (8%). Of the incident
infections, HPV-16 was the most persistent (mean
duration, 18.3 months), followed by HPV-31 and HPV-53
(14.6 and 14.8 months, respectively). HPV-6 and HPV-84
had the shortest mean duration time (<10 months) The
mean durations of incident, same-type LR or HR HPV
infections were 13.4 months and 16.3 months,
respectively. Whereas the majority of episodes with a
type-specific HPV infection cleared within 2 years, there
were many women who were either reinfected with a new HPV genotype or presumably experienced reactivation of
their initial infection.
Prospects for primary prevention of cervical cancer in developing countriesAlberto Cuadrado
The HPV types that cause cervical cancer are sexually transmitted,
but there is little evidence that infection can be avoided
by behavioural changes, such as condom use. In contrast,
prophylactic vaccines against HPV infection are likely to have
high efficacy. In principle, the effectiveness of HPV vaccination
as a strategy for cervical cancer control can be measured
either by monitoring secular trends in cervical cancer incidence
or by conducting randomized trials. The former approach
is unlikely to provide convincing evidence of effectiveness,
since cervical cancer rates are subject to strong secular
trends that are independent of intervention measures. A
few phase III trials of HPV prophylactic vaccines are now
being started. Such trials are very expensive studies involving
frequent and complicated investigations. It is important,
however, to start as soon as possible simpler trials designed
to demonstrate the effectiveness of HPV vaccine in field
conditions, i.e. in developing or intermediate countries which
suffer the major burden of mortality from cervical cancer.
Such trials may capture a difference in the most severe, and
rarest, preinvasive cervical lesions (i.e., the real target of
any HPV vaccine) over a prolonged follow-up (20 years at
least). The design of such studies is briefly considered for
two areas: Southern India and South Korea. This paper is
available at: http://www.insp.mx/salud/index.html
Basics To Ca Cx Screening (Eastern Biotech)Pankaj Sohaney
Detecting HPV means better understanding of the risk of cervical cancer was the major focus of Dr. Dinesh Gupta. He spoke on “Opportunistic Screening for Cervical Precancer Lesions” and informed why the combination screening is vital for prevention and detection of cervical cancer. According to Dr. Gupta, combined screening with liquid based cytology and hybrid capture2 HPV DNA test would identify who’s at risk for high-grade disease and cancer and reduce missed disease caused by false-negative Pap Smear. HPV DNA test is the only FDA approved test to detect 13 high risk HPVs associated with virtually all cervical cancer, he added.
Cancer Biomarkers Research, HPV and Cancer, HPV VaccineJames Lyons-Weiler
An overview of advances in cancer biomarker research strategies, the pathogenesis of HPV virus and a focus on the HPV vaccine with an analysis of evidence of type replacement.
HPV Infection , HPV Vaccination , Cervical cancer , Cancer in India , Dr. SHA...Lifecare Centre
HPV inefection , HPV disease prevention, Cervical cancer prevention , Cervical cancer treatment, Female cancer , Female cancer prevention , Uterine cancer , Cancer in india
Treatment Deintensification in HPV positive head and neck cancerDr Rushi Panchal
This ppt is providing detail of current status and future direction of treatment deintensification strategies of head and neck cancer in era of HPV positive sq cell carcinoma.
HPV Testing is essential in the triage of ASC-US and/or LSIL cytology. The test helps to clearify the situation after treatment of high-grade CIN and to resolve uncertainties after diagnostic and or consecutive treatment. 2016 up to date information is give by the presentation.
Primary HPV testing or co-testin
Anal dysplasia: Diagnosis and Management, OR Everything you ever wanted to kn...CBRC
Screening, treatment and prevention of Anal
Intraepithelial Neoplasia (AIN) Presented by Joel Palefsky, UCSF School of Medicine, San Francisco at the 5th Annual Gay Men's Health Summit held in Vancouver, BC on November 9th and 10th, 2009.
The Natural History of Type-specific Human Papillomavirus Infections in Femal...Alberto Cuadrado
Little is known about the average duration of typespecific
human papillomavirus (HPV) infections and their
patterns of persistence. The objectives of this study were
to evaluate the rate of acquisition and clearance of
specific HPV types in young women. Female university
students (n 621) in Montreal were followed for 24
months at 6-month intervals. At each visit, a cervical
specimen was collected. HPV DNA was detected using the
MY09/MY11 PCR protocol followed by typing for 27
HPV genotypes by a line blot assay. The Kaplan-Meier
technique was used to estimate the cumulative probability
of acquiring or clearing a HPV infection considering
types individually or in high-risk (HR) or low-risk (LR)
groups defined by oncogenic potential. Incidence rates
were 14.0 cases/1000 women-months (95% confidence
interval, 11.4 –16.3) and 12.4 cases/1000 women-months
(95% confidence interval, 10.4 –14.8) for acquiring HR
and LR HPV infections, respectively. The 24-month
cumulative rates of acquisition were highest for HPV-16
(12%), HPV-51, and HPV-84 (8%). Of the incident
infections, HPV-16 was the most persistent (mean
duration, 18.3 months), followed by HPV-31 and HPV-53
(14.6 and 14.8 months, respectively). HPV-6 and HPV-84
had the shortest mean duration time (<10 months) The
mean durations of incident, same-type LR or HR HPV
infections were 13.4 months and 16.3 months,
respectively. Whereas the majority of episodes with a
type-specific HPV infection cleared within 2 years, there
were many women who were either reinfected with a new HPV genotype or presumably experienced reactivation of
their initial infection.
Prospects for primary prevention of cervical cancer in developing countriesAlberto Cuadrado
The HPV types that cause cervical cancer are sexually transmitted,
but there is little evidence that infection can be avoided
by behavioural changes, such as condom use. In contrast,
prophylactic vaccines against HPV infection are likely to have
high efficacy. In principle, the effectiveness of HPV vaccination
as a strategy for cervical cancer control can be measured
either by monitoring secular trends in cervical cancer incidence
or by conducting randomized trials. The former approach
is unlikely to provide convincing evidence of effectiveness,
since cervical cancer rates are subject to strong secular
trends that are independent of intervention measures. A
few phase III trials of HPV prophylactic vaccines are now
being started. Such trials are very expensive studies involving
frequent and complicated investigations. It is important,
however, to start as soon as possible simpler trials designed
to demonstrate the effectiveness of HPV vaccine in field
conditions, i.e. in developing or intermediate countries which
suffer the major burden of mortality from cervical cancer.
Such trials may capture a difference in the most severe, and
rarest, preinvasive cervical lesions (i.e., the real target of
any HPV vaccine) over a prolonged follow-up (20 years at
least). The design of such studies is briefly considered for
two areas: Southern India and South Korea. This paper is
available at: http://www.insp.mx/salud/index.html
Basics To Ca Cx Screening (Eastern Biotech)Pankaj Sohaney
Detecting HPV means better understanding of the risk of cervical cancer was the major focus of Dr. Dinesh Gupta. He spoke on “Opportunistic Screening for Cervical Precancer Lesions” and informed why the combination screening is vital for prevention and detection of cervical cancer. According to Dr. Gupta, combined screening with liquid based cytology and hybrid capture2 HPV DNA test would identify who’s at risk for high-grade disease and cancer and reduce missed disease caused by false-negative Pap Smear. HPV DNA test is the only FDA approved test to detect 13 high risk HPVs associated with virtually all cervical cancer, he added.
Welcoming remarks by Dr Osborne E Nyandiva on Symposium: Cervical cancer and its prevention
Co-Presenter Dr Giama. We are happy to present to you this very crucial discussion on Cancer.
Cervical cancer is a type of cancer that develops in a woman's cervix (the entrance to the womb from the vagina).
Cancer of the cervix often has no symptoms in its early stages. If you do have symptoms, the most common is unusual vaginal bleeding, which can occur after sex, in between periods or after the menopause.
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In this webinar, Dr. Durand will review the changing landscape of HPV-related diseases and cancers. She will discuss methods of HPV prevention for current cancer patients and cancer survivors. Attendees will learn about the evidence for HPV vaccination in adults. Practical tips will be provided on how to access HPV vaccination.
View the YouTube video: https://youtu.be/wFgpmqOpzC4
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Human papiloma virus and its association to Cervical Cancer
HPV in Saudi Arabia .
Currently I am working in Arar Central Hospital, in Arar city
In Saudi Arabia.
Please do not hesitate to contact us if you require any further information.
Alsultany@hotmail.com
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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1. Don’t ASCUS, Don’t Tell:
Nuances of Cervical Cancer Screening
Kathleen McIntyre-Seltman
Magee Womens Hospital
University of Pittsburgh
Women’s Health 2012: The 20th Annual Congress
2. Disclosures
• In the last 2 years I have no conflicts of interest to
disclose
• Prior to this time, I gave lectures for which I was
compensated
– HPV vaccine
– HPV test
• I stopped giving those lectures when policy
required using company slides rather than my
own slides
3. Learning Objectives
As a result of this presentation, the learner will be able to:
• Discuss the epidemiology of HPV, cervical
cancer and pre-cancer
• Compare different strategies for cervical
cancer screening
• Counsel patients regarding new
screening guidelines
4. U.S. Prevalence of HPV Disorders
CA
8000
Cancer Precursor
HSIL
300,000
Trivially Abnormal Pap
ASCUS / LSIL
3 million
HPV INFECTION
9-10 million
5. The 2001 Bethesda System (Abridged)
INTERPRETATION/RESULT
Negative for Intraepithelial Lesion or Malignancy
Epithelial Cell Abnormalities
Squamous cell
Atypical squamous cells (ASC)
of undetermined significance (ASC-US)
cannot exclude HSIL (ASC-H)
Low-grade squamous intraepithelial lesion (LSIL)
encompassing: human papillomavirus/mild dysplasia/cervical intraepithelial
neoplasia (CIN) 1
High-grade squamous intraepithelial lesion (HSIL)
encompassing: moderate and severe dysplasia, carcinoma in situ; CIN 2 and
CIN 3
Squamous cell carcinoma
Glandular cell
Atypical glandular cells (AGC) (specify endocervical, endometrial, or NOS
Atypical glandular cells, favor neoplastic (specify endocervical or NOS
Endocervical adenocarcinoma in situ (AIS)
Adenocarcinoma
Other
AUTOMATED REVIEW AND ANCILLARY TESTING (Include as appropriate)
EDUCATIONAL NOTES AND SUGGESTIONS (Optional)
7. A Brief History of Cervical Screening
Before 1950’s:
• No screening in USA
• Colposcopy for screening in Europe and elsewhere
• Cone for severe dysplasia, hyst for CIS
1950’s – 70’s
• Pap screening
• Women and clinicians socicalized to annual exams
• Colposcopy appears in US
• Office treatment (cryo) of dysplasia
• CIN terminology
• Cause of cervical cancer unknown but known to be
related to sex
8. A Brief History of Cervical Screening
1980 – 90’s
• Early understanding of role of HPV
• The Bethesda System → ASCUS
• Understanding that Paps have lower sensitivity
• Aggressive “search and destroy” of low grade
changes
• LASER (80’s) and LEEP (90’s)
9. A Brief History of Cervical Screening
21st century
• More sophisticated understanding of HPV
epidemiology and natural history
• Distinction between HPV infection and
neoplasia
• HPV vaccination
• Novel approaches to screening
10. What the heck is ASCUS?
Squamous epithelial
cells that look
slightly abnormal but
do not fulfill TBS
criteria for LSIL
11. Risk of High Grade Disease
when Pap is minimally abnormal
PAP Any CIN CIN 3 or
Cancer
ASCUS 20-30% 3-8%
LSIL 50-70% 15-40%
Importance of minimally abnormal pap:
• Detecting high grade disease
• Identifying women at risk to develop high risk disease
12. Triage of ASC - US
what we learned from ALTS
• Approximately half ASC-US is HPV +
• HPV triage of ASC-US is cost effective
• 85% LSIL HPV + therefore HPV triage is not
useful
• ALMOST ALL CIN 3+ in HPV + group
13. What the heck is ASC-H?
Atypical squamous cells
not meeting criteria for
LSIL, but with one or a
very few small cells
suspicious but not
diagnostic of HSIL
14. Triage ASC-H
% HPV + % CIN 2+
ALTS data 84% 50%
Sherman Cancer 2006 108:298
Multi site –CAP review 50% 34%
Davey et al JLGT 14:206 2010
Ince et al 43%
GynOnc 2011 121:152
Univ Pittsburgh 2010 55% 35%
15. Triage HPV
Magee Womens Hospital data
JLGT 14 2010
AGE %HPV+ o <40, approx half HPV+
20-29 58 o >40 approx one third
30-39 42 HPV+
o Approx 1/3 have CIN 2+
40-49 35
o NPV over age 40 100%
50-59 40
60-69 43
16. What is HPV?
DNA virus
circular genome
7 genes
– Early regulatory
– Late capsid assembly
2 capsid proteins coded by L1
and L2
More than 100 types identified
L1 unique to each type
Vaccine = L1 antigen
17.
18. How is HPV Transmitted?
• Almost certainly requires
sexual contact
• Does NOT require
penetrative intercourse
• Skin/mucosa to
skin/mucosa contact
19. Who gets HPV?
• half of women within 3 yrs of starting sex
– 31% get HPV 16
– 20% get HPV 18
• 80% women by age 25
• ~100% of women with > 3 lifetime partners
What about men?
20. It’s easier to get HPV
than to get pregnant!
- Dame Margaret Stanley
21. Prevalence of HPV Infection
in US women
AULT: ClinObstetGynecol, Volume 51(3).September 2008.527-532
22. Prevalence of HPV
Schiffman, M. et al. J Natl Cancer Inst 2003;2003:14-19
Copyright restrictions may apply.
28. Natural History of HPV
0–1 Year 0–5 Years 1–20 Years
Continuing CIN 2/3 Invasive
Infection AIS Cervical
Cancer
Initial
HPV
Infection
CIN 1
Cleared HPV Infection
29. Natural History of HPV Infection
• Clearance of virus (“sustained remission”) 80 –
90%
• Persistent expression of virus: 10 – 20%
These are the women at risk for cancer
Risk factors for persistence:
– Viral type and variant
– Younger age at acquisition
– Smoking
– Immune suppression
– Nutritional? Genetic? Other factors?
30. HPV Type and Cancer Risk
HPV TYPE % cancers % controls OR
HPV 16 53 3.0 434
HPV 18 11 1.0 248
HPV 45 4 0.5 197
HPV 31 3 0.6 123
HPV 52 2 0.2 200
HPV 33 2 0.2 373
Muñoz NEJM 2003
31. Carcinogenesis
• Integration of viral genome
• E6 and E7 alter control of cell growth
– Decrease tumor suppressors
– Increase tumor promoters
– Inhibits apoptosis
– Alter immune response, especially interferon
– Synergism results in cell immortalization
32. Success of Screening
Pap testing has decreased the rate of cervical
cancer by 75% (less in less resourced countries)
BUT:
• Relies on repeated testing (false negative rate of
1 pap between 30 and 50%)
• Requires highly trained cytologists
• Relies on visual pattern recognition
• Expensive
33. Natural History of HPV Infection
• Clearance of virus (“sustained remission”):
80 – 90%
• Persistent expression of virus: 10 – 20%
These are the women at risk for cancer
34. Cumulative Incidence CIN 3/CA
women with normal pap, single HPV test at entry
Khan et al JNC 2005; 97:1072 Pap NL/ASC/LSIL
Kaiser study of 20514 women
35. Development of CIN 3+ in 7 Countries
Dillner, J. et al. BMJ 2008;337:a1754
36. Primary HPV Screening
Rijkaart Lancet Oncol 2012:78
15 year follow up cohort Swedish women, age 30-60, screened q 5 yrs
HPV detected more abnormalities in first screen
HPV Cytol
BASELINE
CIN 2+ 1.34 1.07
CIN 3+ 0.86 0.75
Cancer 0.06 0.03
SUBSEQUENT ROUNDS 0.93
CIN 2+ 0.82 0.93
CIN 3+ 0.45 0.62
Cancer 0.02 0.07
37. Primary HPV Screening
ARTISTIC trial – primary screening in England: f/u after 3 rounds
Kitchener Eu J Cancer 47:2011:864
DETECTION CIN 2+ % of population
HPV CYTOL
Round 1 2.46 2.19
Round 2 0.74 0.89
Round 3 0.77 0.69
HPV - HPV + CYTOL - (nl) CYTOL abn (+)
Round 1 0.17 14.5 0.15 17.7
Round 2 0.27 4.2 0.58 2.26
Round 3 0.42 2.57 0.68 1.21
38. Follow up HPV - women
outcome HPV - HPV- /Pap - Pap -
Kaiser No Cancer/100,000 3.8 3.2 7.5
Cal in 5 y
Kaiser CIN 3+ <1%
Portland
ARTISTIC CIN 3+ 0.48 0.42
Turkey cancer 1/2175 or 0.5%
Kaiser No Calif Katri et al Lancet Onc 2011:12:663
Kaiser Portland Khan et al JNCI 2005
ARTISTIC Kitchener Eu J Ca 2011:864
Sweden Bulkmanset et al 2009
39. Co Test Screening
ARTISTIC trial – primary screening in England: f/u after 3 rounds
Kitchener Eu J Cancer 47:2011:864
DETECTION CIN 2+ % of population
HPV - / cytol - HPV + / cytol + HPV + / cytol - HPV+ /cytol +
Round 1 0 2.23 1.48 32.6
Round 2 0.25 0.44 3.67 5.03
Round 3 0.42 0.48 2.77 2.2
40. Risk of Developing CIN
Cytol - / HPV + women
2020 women CYTOL - HPV + followed: ages 16-81, mean 28
Castle et al Cancer 95:2145 2002
Cytology detection of Pap showing: Cum risk
> ASCUS 16.8%
> LSIL 6.4%
> HSIL 2.2%
RISK FACTORS
• HPV 16/18
• young age
• high viral load
41. Risk of Developing CIN
Cytol - / HPV + women
1138 women followed, mean 54 months, age mean 41
Zhao et al,GynOnc 122:291 2011
HISTOL CIN 1+ HIGH GRADE CIN 2+
Total 24% 2.4%
< 30 27.6% 2.4%
> 30 21% 2.4%
42. HPV Types and Cancer Risk
ALTS trial: Number (%) women developing > CIN 3
2 yr f/u,women > 30, by cytology and HPV status at entry into trial
HPV status ASCUS LSIL
HC and/or PCR
HPV - 2% 5%
Oncogenic HPV + 15% 17%
Oncogenic HPV + / 16 - 8% 11%
HPV 16 + 32.5% 39%
Schiffman et al JNCI 2005
43. Self Collection of HPV
Zhou et al JNCI 2012
13,000 underscreened women in rural China
+ HPV 14.7 vs 15.6 clinician collected
Sensitivity to Detect Disease
SELF CLINICIAN Cytology VIA
HPV HPV
CIN 2+ 83% 95% 72% 48%
CIN 3+ 86% 98% 89% 65%
44. Self Collection of HPV
Zhou et al JNCI 2012
13,000 underscreened women in rural China
+ HPV 14.7 vs 15.6 clinician collected
Comparing Screening Techniques
Detection CIN 2+
SELF CLINICIAN Cytology VIA
HPV HPV
SENS 86 97 81 50
SPEC 81 83 94 87
45. HPV Screening: Summary
• More sensitive than cytology
• HPV q 3 yrs more sensitive than cytology q yr
• HPV testing detects CIN 2+ earlier than
cytology; detection “catches up” with
repeated cytology screening
• Negative predictive value of HPV very high,
meaning that women who are HPV – are
“protected” from dx CIN 3+ for several years
46. Current Screening Recommendations
starting and stopping
• Begin screening no earlier than age 21
• Continue until 65 or 70, then d/c:
– Unless hx CIN 3 or cancer in last 20 yrs
– Unless fewer than 3 paps in lst 10 yrs
• Stop screening after hyst when cervix removed
– Unless hx CIN 3 or cancer
– Continue age appropriate screening if cervix present
47. Current Screening Recommendations
Frequency
• Q 2 years 21-30
• Q 2 years > 30 unless cotesting
– After 3 neg tests, can increase interval to 3 yrs
• Q 3 years at earliest if pap and HPV both neg
48. ARHQ review 2011
When should screening start?
Initiation of screening no earlier than 21
• High prevalence but low persistence in
younger women
• < 25 high proportion false + paps
• Screening < 25 does NOT decrease cervical CA
Vesco KK et al Screening for Cervical Cancer: a systematic evidence review for
USPHSTF
No 86, AHRQ pub no. 11-05156-EF-1
49. ARHQ Review 2011:
Should LBC be recommended?
LBC compared with conventional cytology
• LBC less unsatisfactory Paps
• Possible increase in minor abnormalities
• NO DIFFERENCE in detection CIN 2+
• Unclear whether cost-effective
Vesco KK et al Screening for Cervical Cancer: a systematic evidence review
for USPHSTF
No 86, AHRQ pub no. 11-05156-EF-1
50. ARHQ review 2011:
Should HPV screening be recommended?
HPV primary screening +/- cytology triage
• HPV more sensitive for CIN 2+ (30-50%)
• HPV less specific (3-5%)
• Similar rate of colpo referral with cytol triage
• Less invasive cancer in HPV screened cohorts
Vesco KK et al Screening for Cervical Cancer: a systematic evidence review for
USPHSTF
No 86, AHRQ pub no. 11-05156-EF-1
51. ARHQ 2011:
Should HPV/Pap Cotesting be recommended?
• Cumulative CIN 3+ equal
• CIN 3+ detected earlier
• 50-60% more sensitive than cytol alone
• 5% less specific in women >30
• No impact in women <30
• Minimal benefit compared with HPV screening
Vesco KK et al Screening for Cervical Cancer: a systematic evidence review
for USPHSTF
No 86, AHRQ pub no. 11-05156-EF-1
52. ARHQ review 2011:
Should HPV be used to triage minor
abnormalities?
Triage of minor abnormalities
• Increased detection of CIN 2+ (12%)
• Possible detection of CIN 3+ earlier in women
<30
• Increased referral to colposcopy
Vesco KK et al Screening for Cervical Cancer: a systematic evidence review for
USPHSTF
No 86, AHRQ pub no. 11-05156-EF-1
53. ARHQ review 2011:
What are the harms of HPV testing?
Harms of HPV testing
• Increased anxiety, fear, distress immediately
but resolved at 6 mo f/u
Vesco KK et al Screening for Cervical Cancer: a systematic evidence
review for USPHSTF
No 86, AHRQ pub no. 11-05156-EF-1
54. ARHQ review 2011:
Conclusions
• 21 reasonable age to start screening
• LBC equal sensitivity to CC but may decrease
unsatisfactory slides - ? Cost effectiveness
• HPV primary screening “appears promising”
when paired with cytology triage
• Co testing HPV/Pap similar to HPV only with
cytol triage; does not add to sensitivity
Vesco KK et al Screening for Cervical Cancer: a systematic evidence review
for USPHSTF
No 86, AHRQ pub no. 11-05156-EF-1
55. Cervical Cancer Screening
Future Directions
• Decreased frequency of screening using
cytology only (reflex HPV testing for ASC-US)
ages 21-30: Q 3 years
• Primary HPV screening >30
– Reflex cytology
– Q 3-5 years
56. How can we prevent cervical cancer?
Secondary prevention
• Screen for cancer precursors
• Diagnose and treat cancer precursors
Primary prevention
• Education
• Vaccine
57. Who Needs Referral for Colposcopy?
• Non adolescents with > ASC US HPV +
• Women > 30 with HPV Pap screening
– ASCUS: IF HPV 16/18 +
– ASCUS: IF either Pap or HPV abnormal after 1 yr
• Menopausal women: can repeat LSIL if desired – or HPV
test – or colpo
• ANY AGC
58. How can we prevent cervical cancer?
Secondary prevention
• Screen for cancer precursors
• Diagnose and treat cancer precursors
Primary prevention
• Education
– GET WOMEN TO BE SCREENED
• Vaccine
59. HPV Vaccines
• Gardasil®
– Quadrivalent against 6/11/16/18
– FDA approved 2006 for women ages 9 – 26
– FDA approved 2009 for men
• Cervarix®
– Bivalent against 16/18
– FDA approved 2009
• Both synthetic VLPs
• Both given time 0, 2 mo, 6 mo
60. Efficacy of Vaccine
% decrease
Women neg for all vaccine viral types >99%
Women pos for at least 1 viral type OR 40 – 60%
off protocol (missed or late doses)
Similar for bivalent and quadrivalent vaccines
• Cross protection in phylogenetically related HPV families
• Bivalent or quadrivalent vaccine 59% in CIN 2/3 due to
HPV 31/45
61. Summary
• HPV is necessary but not sufficient for cancer
• Everybody gets HPV, but most people clear the infection
• Current screening with cytology has limitations
• Primary HPV screening is the future, likely with cytology
triage
• Vaccination is a safe and effective way to prevent HPV
related disease
• Rapid HPV test self collected specimen combined with
VIA /treat in underresourced environments is cost
effective
CERVICAL CANCER CAN BE NEARLY ELIMINATED!