Dysplasia, Malignancy, and Infertility

___________ cancer is the most common gynecologic malignancy in the US

Endometrial

What are CIN risk factors?

Same as HPV plus.... Smoking, OCP use, Parity, Black, hispanic, immunosuppressed, inadequate screening, older, and vitamin deficiencies (A,C,E,B carotene and folic acid)

90% of vulvar cancers are....

squamous cell carcinoma

What is a latent HPV infection?

´HPV remains quiescent ´No tissue effects ´Not actively replicating

What is the treatment for HPV?

´In general, none ´Positive health behaviors (smoking cessation) ´Management of immune compromise ´Treatment of sequelae-symptomatic warts, high grade neoplasia, invasive cancer

How can you directly detect HPV DNA?

´In situ hybridization ´Nucleic acid amplification testing (NAAT) ´Polymerase chain reaction (PCR)

How is ovulation induced by gonadotropins? When will this not work?

´Injection of FSH/LH ´ monitoring of estradiol levels & follicular development on ultrasound ´When follicles are mature, hCG is administered to induce ovulation (mimic effects of LH) Ineffective if decreased ovarian reserve

What is the treatment for genital warts caused by HPV?

´Mechanical removal or destruction ´Topical immunomodulators Chemical or thermal coagulation

What are the follow up recommendations for vaginal invasive lesions?

´Monitor vaginal cytology and vaginoscopy 2-4 months after tx ´Cytology with/without vaginoscopy every 6-12 months Long term cytology

What is Type 1 vs Type 2 uterine cancer?

´Most are type I endometrioid adenocarcinomas that are Estrogen dependent, low grade, derived from endometrial hyperplasia ´Type II-serous or clear cell histology, more aggressive

FIGO Vulvar cancer staging

1- confined to vulva 2- adjacent perineal structures 3- (+) nodes 4- invades other regions

What is the treatment for VAIN 1? VAIN2/3?

1= observe, can spont regress 2/3= excise, CO2 laser ablation, topical FU, or radiation

After treatment for HGSIL, routine screening should continue for at least _____ years (even if extends beyond age 65)

20

When does HPV testing begin?

> 30yo Not indicated in < 25yo or hysterectomy *different from PAP smear- pap tests for precancarous cells, not the virus itself!!!*

In pregnancy it is okay to defer treatment for ________ or ________ until 6 weeks postpartum. What diagnostic tests are okay to perform in pregnancy?

ASCUS and LSIL Colposcopy and ectocervical biopsy okay

What are the two treatment options for Cervical Intraepithelial Neoplasia?

Ablation of entire T-zone and lesion (for noninvasive) or Excision of entire T-zone and lesion (increased risk of PTL)

What two solutions are used during colposcopy?

Acetic acid - turns white- biopsy there! Lugol Iodine solution - stains normal cells dark purple, any abnormal will not change color- biopsy there!

When can you stop screening for cervical cancer?

Age 65 if normal screenings for past 10 years or After hysterectomy with removal of entire cervix and no Hx of high risk lesions

Most common cytological abnormality; risk of CIN2-3 is 5-10%

Atypical squamous cell of undetermined significance (ASCUS)

What tumor marker indicates advanced disease in uterine cancer?

CA125

This cervical pathology is usually transient, has high rates of spontaneous regression, and is generally not treated, but rather monitored.

CIN 1 - low-grade squamous intraepithelial lesion

CIN 1 confined to the ________. CIN 2 confined to the _______. CIN 3 or carcinoma in situ extends the ____ ________.

CIN 1 confined to the lower 1/3 CIN 2 confined to the lower 2/3 CIN 3 or carcinoma in situ extends the full thickness

This cervical pathology usually occurs de novo, has significant malignant potential and is generally excised.

CIN 2 and CIN 3 - high-grade squamous intraepithelial lesion (CIN3 is treated regardless of age)

How can the dx of HPV be confirmed?

Can only be confirmed by detection of HPV nucleic acids by NAAT, PCR, in situ hybridization

What Nonneoplastic findings can a Bethesda system cytology report show?

Cell variations Reactive cellular changes Organisms (bacteria, virus, yeast, fungi) Other malignant neoplasms

Most common gynecologic cancer in women worldwide that stems from HPV

Cervical

This pre-invasive, precancerous lesions of the squamous epithelium caused by HPV.

Cervical Intraepithelial Neoplasia (CIN)

If anovulaiton is causing infertility, what is the treatment?

Clomiphene citrate (Clomid) Induces ovulaiton

Procedure performed in the office setting allowing visualization of the cervix and vagina with a microscope to identify and direct a biopsy. It is the gold standard evaluation of abnormal cervical cytology. Cervicitis is a contraindication.

Colposcopy

What should you do if the pap smear report comes back with Atypical glandular cells (AGC)?

Colposcopy and endocervical sampling

Clear cell adenocarcinoma of the vagina is likely due to in utero exposure of...

DES

A diagnosis of Squamous cell carcinoma or adenocarcinoma on results report requires _______.

Excision

What is the management for a woman with biopsy-confirmed CIN 2 or 3 after an adequate colposcopy?

Excision or ablation Cotesting at 12 and 24 months Repeat at 3 years and regular screening after

What vaccine against HPV is available in the US? What strains does it cover?

Gardasil HPV9 6, 11, 16, 18, 31, 33, 45, 52, and 58

This prevents new HPV infection by blocking entry into host cells and potentially prevents malignancies at cervix, vagina, penis, anal canal, and oropharynx, but does does not resolve preexisting infection

HPV Vaccine

What are some Cervical Cancer Risk Factors?

HPV infection Not having adequate screening Smoking Immunosuppressed Parity- 7 prior full term pregnancies had 4x risk of cancer Long-term COC use More than 6 lifetime partners Early age of first intercourse (prior to age 20)

When is HPV testing not indicated?

HPV testing is NOT indicated in women younger than 25 yrs old or for women with a complete hysterectomy

What prevents vulvar cancer?

HPV vaccine Smoking cessation Optimization of immunity

Preinvasive lesions can spontaneously regress, remain stable, or progress. What preinvasive lesions are less likely to regree?

High grade- CIN3

Persistent infection of ______ HPV is necessary for the development of neoplasia.

High risk

HPV type 16, 18, 31, 33, 35, 45, and 58 are considered ______ risk types. What do they cause?

High risk Can cause cervical dysplasia and cancer

Most common sexually transmitted disease in the United States

Human Papillomavirus

What is the preferred tx for adenocarcinoma in situ when future fertility is not desired

Hysterectomy but not completely protective

What should you do if the pap smear report comes back with Atypical squamous cell of undetermined significance (ASCUS)?

If too young to HPV test, repeat in 1 year. If > 30, get HPV cotest followed by Colposcopy.

Where does HPV infect?

Infect squamous or metaplastic epithelial cells

What are the components of the 2014 Bethesda System Cytology Report?

Interpretation/Results Adjunctive testing Computer assisted interpretation Notes/Comments

If there is a male factor causing infertility, what is the treatment?

Intrauterine insemination Intracytoplasmic sperm injection to egg (IVF) Donor sperm

HPV type 6 and 11 are considered ______ risk types. What do they cause?

Low risk Can cause genital warts, laryngeal papillomas

Cytological features of HPV infection and CIN1 is ______ grade

Low-grade squamous intraepithelial lesion (LSIL)

Where does cervical cancer metastasize to?

Lung Liver Ovaries Bone

In a PCOS patient who wishes to become pregnant, what medication is indicated for insulin resistant patients?

Metformin: Lowers insulin levels in insulin resistant patients (with PCOS), increases spontaneous ovulation and response to clomiphene citrate

Who is most likely to clear HPV?

Most HPV infections spontaneously resolve in 1-2 years in younger women Age <21 clearance occurs on average of 8 months with range of 8-24 months

What are the fetal risks of ART?

Multiple gestation PTL SGA Congenital abnorms, epigenetic issues

Atypical glandular cells (AGC) have a high risk of....

Neoplasia Increased risk of endometrial and other reproductive tract cancers as well as breast and colon cancer

What is the MC risk factor for uterine cancer?

Obesity- d/t excess estrogen

What are the maternal risks of ART?

PEC Previa Placental disruption

____________ screening has reduced the incidence and mortality rate from invasive cancer by more than 70%

Papanicolaou (Pap)

What are the Vulvar Cancer Surveillance recommendations?

Pelvic exam and lymph node palpation every 3 months for 2-3 years and then every 6 months until 5 year mark, then annually

When may an unsatisfactory sample come back on a cytology report?

Perimenopause- d/t atrophy of the tissue or infection

What is the appropriate next step for a woman whos results read ASCUS?

Repeat cytology in 1 year or HPV testing (if > 30) If ASCUS after 1 year or HPV test + then go to colposcopy

What is the treatment for Uterine cancer? What if it is more advanced?

Surgery-hysterectomy+BSO Advanced= Chemo+radiation post op If not Sx.....Radiation or hormones

What are the adverse effects of Gardasil?

Syncopal episodes- observe for 15 mins post vaccine Local reactions

The _______ tool samples the ectocervix. The _______ tool samples the endocervical canal. The _______ tool samples both the endo and ectocervical epithelia simultaneously, only with liquid cytology.

The ___spatula____ tool samples the ectocervix. The ___brush____ tool samples the endocervical canal. The ___broom____ tool samples both the endo and ectocervical epithelia simultaneously, only with liquid cytology.

This is the location of normal squamous metaplasia that occurs at the squamocolumnar junction where columnar cells are replaced by squamous epithelium on the cervix

Transformation (T) zone

What is a transient vs persistent HPV infection?

Transient ´HPV infection clears after several months/years Persistent ´HPV infection does not clear and stays present for years

This rare type of cancer is diagnosed over the age of 70 years old, not ususally a primary lesion, develops slowly, MC due to HPV 16, and increased risk with other gyn cancers.

Vaginal invasive lesions

This cancer is diagnosed in elderly caucasian women, has a poor prognosis, diagnosed by biopsy, staged by TMN staging, and treated by excision or immunotherapy.

Vulvar Melanoma

This is most commonly diagnosed at early stages, is found in older women, diagnosed by biopsy, and treated with excision or chemo/rad.

Vulvar cancer

More frequent cervical cancer screening needed in what patients?

Women who have a history of cervical cancer, are infected with human immunodeficiency virus (HIV), immune suppressed, or exposure to diethylstilbestrol (DES) before birth

A woman who was vaccinated at age 12 for HPV refuses her PAP smear at age 21. What should you counsel her on?

Women who have been vaccinated against HPV still need to follow the screening

____________ cells line the ectocervix and vagina. _______ cells line the endocervix.

___squamous___ cells line the ectocervix and vagina. ___columnar___ cells line the endocervix.

Any suspicious cervical lesion, evaluate it by.....

cervical biopsies-need to do this for any suspicious lesion (via colposcopy or conization)

What should you do if the pap smear report comes back with Low-grade squamous intraepithelial lesion (LSIL)?

colposcopy is indicated in women aged 25 and up ´If HPV negative on a cotest, can repeat a cotest in 1 year or perform colposcopy ´For postmenopausal women, if no HPV cotest, can repeat cytology in 6 and 12 months, perform HPV testing, or colposcopy

What should you do if the pap smear report comes back with HIgh-grade squamous intraepithelial lesion (HSIL)?

colposcopy regardless of age or HPV status

When can Gardasil be given? What types of cancer does it prevent?

males and females, 9 through 26 years of age Prevention of precancerous and cancerous lesions of the: Cervix, vulva, vagina, and anus in women Anal cancer in men Prevention of genital warts in men and women

What is the difference between cancers found in the ectocervix vs endocervix?

´70% squamous cell cancers-arise from ectocervix, incidence is declining, subdivided into keratinizing and nonkeratinizing cancers ´25% adenocarcinoma-arise from endocervix, more occult and diagnosed in later stages

What is the difference between CIN 1, 2, 3, and Full thickness?

´CIN1/mild dysplasia-abnormal cells confined to lower 1/3 of squamous epithelium, also called low grade squamous intraepithelial lesion (LGSIL) ´CIN2/moderate dysplasia-abnormal cells extending into the middle 1/3 ´CIN3/severe dysplasia-abnormal cells extending into upper 1/3 ´CIS-full thickness involvement (in situ)

Why is a lesion in the columnar epithelium usually bad?

´Cervical columnar epithelium is only one cell-layer thick and precancerous lesions here are called adenocarcinoma in situ. ´Untreated, this can progress to invasive adenocarcinoma

What is an expressed HPV infection?

´Creates infectious viral particles ´Causing preinvasive disease or malignancy ´Subclinical or cause warts

How is HOV spread?

´Direct skin to skin contact, mucous membranes, or contact with body fluids of infected individual

What are risks for HPV infection?

´Early age of sexual debut ´Multiple sexual partners ´Smoking ´HIV History of sexually transmitted disease

When is Endocervical sampling indicated?

´Evaluates endocervical canal beyond colposcope's view ´Indicated if colposcopy is inadequate

What is the Follow-up Treatment for Cervical Cancer?

´Evaluation every 3-months for 2 years, then every 6 months until 5 years, and then annually ´Pelvic examination ´Manual nodal survey ´Neck, supraclavicular, axillary, and inguinal lymph nodes ´Cervical or vaginal cuff Pap test if had a hysterectomy

What are the recommendations for Uterine Cancer-Surveillance?

´Most patients can be followed by pelvic exams every 3-6 months for the first 2 years and then every 6-12 months thereafter ´Pap testing is not part of the surveillance ´More advanced cases-following serum CA-125 levels

Primary vs Secondary infertility

´Primary infertility=No prior pregnancies ´Secondary infertility=Infertility following at least one prior conception

How can uterine cancer be prevented?

´Weight loss ´Progestin supplementation ´Genetic testing for Lynch syndrome

What are Lifestyle Therapies for infertility treatment?

´Weight optimization (avoid being over or underweight) ´avoid excessive exercise ´Nutrition ´Stress management

What are the PAP smear and HPV test guidelines?

´Women aged 21-29 years should have a Pap test alone every 3 years. HPV testing is not recommended. ´Women aged 30-65 years should have a Pap test and an HPV test (co-testing) every 5 years (preferred). It also is acceptable to have a Pap test alone every 3 years.

What should you do if the pap smear report comes back with ASCUS, cannot exclude HSIL?

´colposcopy regardless of age or concurrent HPV test result ´If colposcopy is inadequate, diagnostic excision is recommended