Sexually Transmitted Infections and Vaginitis Flashcards

Question

Neisseria gonorrhoeae Resistance

Answer 1

* **Resistant to PCN** * Due to **beta lactamase** or **altered affinity of penicillin binding proteins** * **Resistant to tetracycline** * Ass. w/ **Tet-m** ⇒ ∆ ability to block binding and/or displace tetracycline from 30S subunit of ribosome * **Quinolone resistance also widespread** * Gonorrhea has **shown resistance to every single class of abx** *Neisseria gonorrhoeae* now 1 of 3 resistant organisms CDC has categorized as “**Urgent**”

Answer 2

* _Uncomplicated gonococcal infections of the cervix, urethra, and rectum_ * **Ceftriaxone** 500 mg IM single dose * If _Chlamydia infection_ has not been ruled out ⇒ **dual therapy** * Add **Doxycycline** 100 mg BID for 7 days * Azithromycin no longer recommended b/c of developing resistance * Sex partner(s) should also be evaluated and treated

Answer 3

* **3^rd gen cephalosporin** * Resistant to cephalosporinases * **Binds transpeptidase** & other binding proteins ⇒ **⊗ cell wall synthesis** * All beta lactams can cause **hypersensitivity reactions** * At high doses, beta lactams can cause **seizures**

Answer 4

* Same class tetracycline * **Binds 30S subunit** ⇒ blocks AA-linked tRNA from binding to the “A” site of the ribosome ⇒ **⊗** **protein synthesis** * **GI upset and photosensitivity** are most common AEs * Can cause **esophageal irritation** * Should be administered w/ water * Pts instructed to sit upright for 30 mins after admin * All tetracyclines can cause **discoloration of the teeth** * **Contraindicated in pregnant women and children under 8** * Tetracyclines can **chelate ions** * Should not be administered w/ calcium, iron, antacids, or multivitamins * **No dose** **∆** **for renal or hepatic function**

Answer 5

* Immune response is **Ab mediated** * **PMNs** effective at killing many strains * _Long-term immunity and cross-reactive immunity to other strains does not exist_ * **Reinfection is common** * **Condoms are effective barrier method**

Answer 6

* **Intracellular bacteria** w/ a complex lifecycle * Two biovars: **trachoma** and **lymphogranuloma vereum** * LGV w/ further subdivides into serovars based on Ag differences * Ass. w/ different clinical syndromes

Answer 7

**Elementary body (EB)** and **reticulate body (RB)** EB resistant to environmental conditions much like a spore.

Answer 8

* **Found worldwide w/ no seasonal incidence** * Different serovars ⇒ different types of disease ⇒ different prevalence rates depending on region * _Diseases include:_ * Trachoma * Urogenital infections (STDs) * 1.4 million infections in the US * Adult inclusion conjunctivitis * Newborn inclusion conjunctivitis * Lymphogranuloma venereum (LGV)

Answer 9

* Bacteria target **columnar epithelial cells** ⇒ **acute → chronic inflammatory response** * Infection freq. **remains sub-acute** ⇒ unnoticed and untreated * Trachoma ⇒ limited health resources * **Unique life cycle** protects from immune response

Answer 10

* Caused by the **trachoma biovar** of Chlamydia trachomatis * **Leading cause of preventable blindness in the world** (60 mil cases) * Endemic in _Africa, Middle East, South Asia and parts of South America_ * Eye to eye transmission via **droplet, hands, flies, fomites** * **Repeated infections from childhood** * Chronic inflammation → eyelids turn inward ⇒ eyelashes abrade cornea ⇒ **scarring, pannus (vessel formation in cornea) and loss of vision**

Answer 11

* Occurring in **adults w/ genital infections** caused by C. trachomatis * Probably **auto-inoculation** * **Muco-purulent discharge, keratitis** * Can result in **scarring** if not treated

Answer 12

* C. trachomatis acquired by **passage through infected birth canal** * Occurs **1-2 wks after birth** * **Swelling of eyelids, purulent discharge** * Untreated may lead to **interstitial PNA**

Answer 13

* In woman, **up to 80% asymptomatic** * Can become symptomatic and include **cervicitis, salpingitis, endometritis** * In men, **25% are asymptomatic** * **Urethritis** characterized by **discharge** _not quite as mucopurulent as that of N. gonorrhoeae_ but cannot be distinguished from it * These Infections frequently occur together

Answer 14

* **Urethritis, conjunctivitis, arthritis and lesions** * Occurs in some men * Probably initiated by sexual transmission of Chlamydia

Answer 15

* **Chronic STD** that occurs mostly in _tropical, developing countries_ * *Chlamydia trachomatis* **serovars L1-3** * **Primary lesion on genitals** of man or woman, **small painless**, often unnoticed, heals spontaneously * Followed by **inguinal lymphadenopathy** w/ formation of "**bubos**" ⇒ inflamed painful LNs, inguinal most common, containing the organism * Bubos contain infected, purulent material that **must be aspirated or they may rupture** * Includes fever, myalgias, systemic sx

Answer 16

* **Gram stain** * In symptomatic pts, look for PMNs but no gonocci present (presumptive) * **Ag detection** * Usually EIA or immunofluorescence from direct specimen * Most effective w/ symptomatic urethral specimen in males * Also LGV, neonatal PNA * **NAAT** * Test of choice for STIs * First void urine or urethral or cervical specimens

Answer 17

* **Intracellular organisms** that require **CMI** * Also **causes the pathology** * No long-lasting immunity * **Reinfection** leads to more vigorous immune response and pathology * _Need abx that penetrate cells_ * **Macrolides** * 7 day course of tetracycline or usu. **doxycycline** * Or a single dose of **Azithromycin** * Dual-therapy w/ Ceftriaxone for Gonorrhea * **Condoms** can protect against STD * ID sex partners and f/u * Screen high risk populations

Answer 18

* **Small pleomorphic gram ⊖ rods** * **Sexually transmitted** * **Usually dx in men** because **women are asymptomatic** * **Endemic** in many parts of the world but _uncommon in developed countries_ * Frequently seen in **HIV infected men**

Answer 19

**Chancroid** * **5-10 days incubation** * **Tender raised lesion** w/ **erythematous base** develops in the _genital area_ * Lesion **ulcerates** and becomes **painful** within a few days * Has **soft ragged margins** in contrast to the lesion of syphilis * Lesion **resolves in 1-3 months**

Answer 20

* Specimen from _base of lesion_ * Visualized by **gram stain and microscopy** * Cultured on **specialized agar**, but organism is **fastidious** so not always successful

Answer 21

Several abx options including **azithromycin** or **ceftriaxone** ## Footnote **Drain involved nodes**

Answer 22

* Infection w/ HSV is **life-long** * **HSV type 1** * ~60% sero-prevalence overall * Close to 90-100% in middle-aged adults * **HSV type 2** * ~20% sero-prevalence * ↑ w/ higher number of sexual partners and hx of other STIs * ↑ w/ age * More common in **women** * \> 50 mil in the US have **genital HSV 1/2**

Answer 23

HSV-1/2 are **double-stranded DNA human herpesviruses**

Answer 24

* **Direct contact w/ mucosal surfaces** * Oropharynx, vagina, rectum, cervix, and conjunctivae * **Asymptomatic transmission** possible

Answer 25

* HSV 1 and 2 cause a variety of clinical presentations and can have overlap: * Most people are **asymptomatic** * **HSV-1** usually causes **herpes labialis (cold sores)** * However, increasingly seen in anogenital disease * **HSV-2** usually causes **genital herpes** * Stages of HSV infection include: **primary, latent, and recurrent**

Answer 26

* **Primary genital HSV** * Classic sx is **painful genital ulcers or vesicles** – generally _multiple_ * **Local lymphadenopathy** * ± **Fever** and **headache** * **Oral HSV** can include **gingivostomatitis** and **pharyngitis** * Sx can range from _very mild to severe_ * **Latent HSV** * Can have **no further episodes** after 1° infection * **Recurrent HSV** * Can have **over 3 reactivations per year** * Usually **recurrence sx are milder** than 1° infection sx * Complications can include **meningitis** and **proctitis**

Answer 27

* Usually **diagnosed clinically** based on **appearance of lesions** * _Can directly swab lesion for HSV-1/2_ * **HSV DNA by PCR** – sensitivity higher than culture and more rapid * **Viral culture** – only 50% sensitivity * ↓ Viral detection as lesion heals and lower in recurrence * HSV shedding can be intermittent * **⊖** **PCR or culture does not mean HSV infection is not present** * _Serologic blood tests_ * **Type-specific glycoprotein (gG)** ⇒ assay of choice * **⊖** **Serology w/ active HSV lesion** ⇒ consistent w/ **new infection** * _Serology not recommended for routine screening_ (helpful in specific settings) * **HSV-1 serology** can reflect **oral or genital infection** * **HSV-2 serology** is consistent w/ **genital infection**

Answer 28

* **Acyclovir** 400 mg PO TID for 7-10 days * **Acyclovir** 200 mg PO 5x/day for 7-10 days * **Valacyclovir** 1 g PO BID for 7-10 days * **Famciclovir** 250 mg PO TID for 7-10 days

Answer 29

* **Acyclovir** 400 mg PO BID * **Valacyclovir** 500 mg or 1 g PO qDay * **Famciclovir** 250 mg PO BID

Answer 30

* **Nucleoside analogues** * ℗ by _viral_ _thymidine kinase_ * Affinity is 200x greater for viral thymidine kinase vs. mammalian thymidine kinase * After **acyclovir-monophosphate** formed, _cellular kinases_ ℗ further → **acyclovir triphosphate** * Compound acts as **a substrate and an inhibitor of viral DNA polymerase** * Acyclovir-℗³ **incorporated into DNA** ⇒ **terminates chain elongation** * Generally **safer drugs** * **Important to stay hydrated** to avoid **crystalluria**

Answer 31

* Can be seen in multiple STIs * **Syphilis, HSV, chancroid, lymphogranuloma venereum**, (and Granuloma Inguinale [donovanosis]) * Generally classify based on: * _Pain_ * **Painful** ⇒ HSV or chancroid * **Painless** ⇒ syphilis * _Number of lesions_ * **Single** ⇒ syphilis or chancroid * **Multiple or grouped** ⇒ HSV

Answer 32

* Infections characterized by **dysuria, burning, and urethral /cervical discharge** * Discharge can range from **minimal to frank pus** * Usually categorized as: * **Gonococcal** ⇒ caused by ***Neisseria gonorrhoeae*** * Can be seen on Gram stain * **Nongonococcal** ⇒ ***Chlamydia trachomati****s* is a major one * Others: *Mycoplasma genitalium, HSV, T. pallidum, adenovirus, Ureaplasma urealyticum* * ***M. genitalium*** is 15-25% of cases of nongonococcal urethritis in men in U.S. * Generally treat **symptomatic urethritis empirically** (for gonorrhea and chlamydia) while waiting for results

Answer 33

* **Spectrum of inflammatory disorders of upper female genital tract** * **Endometritis, salpingitis, tubo-ovarian abscess, pelvic peritonitis** * Basic pathogenesis is an _ascending infection_ from cervix → uterus → fallopian tubes and ovaries * _Can spread outside the reproductive organs_ ⇒ **pelvic peritonitis** and rarely **inflammation of the liver capsule** w/ development of **adhesions** (Fitz-Hugh-Curtis syndrome)

Answer 34

Implicated causes: * **Gonorrhea and Chlamydia** * **Normal vaginal flora** (anaerobes, G. vaginalis, H. influenzae, enteric GNRs, S. agalactiae) * **CMV, M. hominis, U. urealyticum, M. genitalium**

Answer 35

* All women w/ PID should have **gonorrhea, Chlamydia and HIV testing** * **Dx can be difficult** * Wide variation in sx * May have mild sx * _Clinical dx_ depends on **pre-test suspicion** * **Abnl bleeding, dyspareunia, vaginal d/c** * **Pelvic or lower abd pain** * **Laparoscopy** may be helpful * _Sexually active women at risk for PID should be **treated empirically** if they have:_ * **Pelvic or lower abdominal pain w/ no other cause identified as one or more:** * Cervical motion tenderness * Uterine TTP * Adnexal TTP * _One or more of these ↑ specificity_: * Fever \> 101°F * Abnl cervical or vaginal mucopurulent d/c, ↑ WBCs in vaginal fluid * ↑ ESR or CRP * Cervical infection w/ gonorrhea or Chlamydia

Answer 36

* Sexually active women at risk for PID should be **treated empirically** * PID usu. caused by Gonorrhea, Chlamydia and bacterial vaginosis organisms predominantly * Treatment should cover **Gonorrhea, Chlamydia, anaerobes, GNRs and strep** * **Parental tx** recommended for _emergencies, in pregnant women, pts unable to tolerate oral therapy_ * **IV therapy** used _until sx abate_ then **pt switched to PO therapy** * **Cefotetan** 2 gram IV every 12 hours + **Doxycycline** 100 mg orally or IV every 12 hours * Or * **Cefoxitin** 2 gram IV every 6 hours + **Doxycycline** 100 mg orally or IV every 12 hours * **Intramuscular and oral therapy** * PO therapy can be considered for women w/ _mild to moderately severe acute PID_, or _after sx abate w/ IV therapy_ * _Several possibilities including:_ * **Ceftriaxone** 250 mg IM in a single dose PLUS * **Doxycycline** 100 mg PO BID for 14 days * ± **Metronidazole** 500 mg orally twice a day for 14 days * Add if you suspect anaerobes, but also good for bacterial vaginosis which very often accompanies PID * or * **Cefoxitin** 2 g IM in a single dose PLUS * **Probenecid** 1 g orally administered concurrently in a single dose * Prolongs action of cefoxitin by ⊗ secretion via renal anion transporter * **Doxycycline** 100 mg orally twice a day for 14 days * ± **Metronidazole** 500 mg orally twice a day for 14 days

Answer 37

* **2^nd gen cephalosporins** * Categorized as **cephamycins** * Similar activity as 2^nd gen cephalosporins **except for activity vs anaerobes in the GI tract** * Used for **surgical prophylaxis** in abd surgery and **abd and pelvic infections** * _Adverse effects:_ * **AE similar to the beta lactams** * **Thrombophlebitis** after IV injection * **Cefotetan** has a _methylthiotetrazole group_ * **Disulfiram like reaction w/ ethanol** * **⊗ Vitamin K production** ⇒ prolonged bleeding time

Answer 38

**Disorder of the vagina characterized by inflammation or irritation of the vulva w/ abnl vaginal discharge.** * Frequent **cross contamination** of nl and pathogenic flora b/t vaginal, urinary, and GI tracts * _In pregnant women_, vaginitis ass. w/ **↑** **risk of miscarriage, pre-term delivery, and infections post-delivery** * **↑ Likelihood of acquiring a STI** upon exposure including HIV

Answer 39

* Vaginal tract **lacks a cleansing mech.** to flush out microbes * Mucus from cervix, cycle dependent * **Main defense** is **low pH (4-4.5) and high numbers of normal flora** * Predominant genus is **Lactobacillus spp** * **Gram** **⊕** **rods**, **facultative or microaerophilic** * Bacterial fermentation of _glycogen_ _→_ _lactic acid_ ⇒ low pH * Glycogen deposited in vaginal epithelial cells in response to estrogen * Produce **hydrogen peroxide** * Defense vs pathogens

Answer 40

* _Pre-puberty and post-menopausal_ * **Scant flora** * **Some lactobacilli** and other orgnaisms derived from skin and GI tract * _Child-bearing years_ * **Predominantly lactobacilli** * Some **yeast** * Bacteria that tolerate low pH * Some **aneaerobes**

Answer 41

* Most common causes of _vaginitis__:_ * **Trichomonas vaginalis** ⇒ Trichomoniasis * **Candida albicans** ⇒ Candida vulvovaginitis * Most common causes of _bacterial vaginosis:_ * **Gardnerella vaginalis** * **Mobiluncus spp** (anaerobic) * **Prevotella spp** (anaerobic)

Answer 42

* Vaginitis is the **inflammation of the vagina** * Ass. w/ **itching, burning, painful urination, odor, and vaginal discharge** * Odor and discharge _vary in amount and type_ depending on etiologic agent * Discharge may consist of **inflammatory cells, epithelial cells, cell debris, and microbes** * Different from urethritis, but overlap of sx and micro

Answer 43

* **Most common vaginal infection in women of child bearing age** * ~ 29% of women in the US are affected * Results from **overgrowth of normal flora** in the vagina ⇒ **polymicrobial** * Risk factors: multiple or new sexual partners, IUD, recent abx use, **vaginal douching**, and **cigarette smoking** * Role of sexual intercourse is poorly understood * Not thought to be sexually transmitted and celibate women may contract it * While **not contagious**, there may be a **spread of bacteria between sexual partners that may predispose to the condition**

Answer 44

* ~85% of women are **asymptomatic** * Most common sx are **fishy odor** and **thin gray-white discharge** * Both are more noticeable after sexual intercourse

Answer 45

* **↓** **Lactobacilli (gram ⊕ rods, aerobes)** * Usually present in high numbers in vaginal flora * **Concomitant ↑ in anaerobes** * Previously ass. w/ ↑ **Gardnerella spp** (gram variable, facultative anaerobe) * Now ass. w/ overgrowth of **multiple anaerobic organisms** including **Mobiluncus** and **Prevotella** spp (gram ⊖)

Answer 46

* Pelvic exam w/ ⊕ Whiff test * When **KOH** comes into contact w/ discharge fluid, a **“fishy” or amine odor is detected** * Laboratory detection of **“Clue Cells”** (epithelial cells covered w/ gram variable organisms)

Answer 47

* **Polymicrobial syndrome** resulting from replacement of normal H₂O₂ producing bacteria in the vagina w/ high concentrations of anaerobic bacteria * **Many cases resolve on their own** * May be treated by **metronidazole PO or clindamycin cream** * Benefits of therapy include **relief of sx,** **↓** **risk of infectious complications s/p abortion/hysterectomy,** **↓** **risk of other infections** (HIV and other STIs) * **50% experience recurrent sx within 12 months** and need a 2^nd course of abx * _Recommended regimen:_ * **Metronidazole** 500 mg PO BID for 7 days * Or * **Metronidazole gel** 0.75% one full applicator (5g) intravaginally for 5 days * Or * **Clindamycin cream** 2% one full applicator (5g) intravaginally for 7 days

Answer 48

* Derivative of lincomycin * **Effective against anaerobes** that participate in **mixed infections** * MOA similar to erythromycin * Clindamycin cream tx may have **fewer adverse effects** vs metronidazole PO * **Tx w/ creams is not recommended in pregnant women**

Answer 49

* _Clinical manifestations_ * Often **asymptomatic** * Minimal discharge; usually has a **fishy odor** * May have **mild vulvar irritation** * _Risk factor_ * Most often occurs in **sexually active women** * _Physical exam_ * **Gray to white, adherent, thin discharge** * May have **minimal vulvar erythema** * _Vaginal pH_ * **4.5-6** * _Wet mount_ * Large number of **clue cells** * _“Whiff test”_ * **⊕** * _Treatment_ * Metronidazole (7 days)

Answer 50

* **Motile protozoan parasite** * Exists in **flagellated trophozoite** form w/ **short undulating membrane** * **Anaerobic** * Multiplies by **longitudinal binary fission** * Placed in vagina or urethra primarily by **sexual intercours**e, transmission by **fomites** possible * Infects ~ 3.7 million but **only ~30% are symptomatic** * Presentation may be related to overall status of host * **Older women** more likely to be symptomatic

Answer 51

* _Men_ * Primarily **asymptomatic carriers** * May experience **urethritis** or **prostatitis** * _Women_ * May be **asymptomatic** * Can have a **scant, watery discharge** * ± Extensive inflammation ⇒ **erosion of vaginal epithelial lining** * **Purulent discharge (white or yellow)** * Vaginal itching and burning * Painful urination * Discomfort during intercourse

Answer 52

Organisms may be **visualized in discharge fluid** or in **PAP smears** **Nucleic acid probe assay** is also available

Answer 53

* **Metronidazole** is drug of choice for _male and females_ * **Sex partners must be treated** to avoid reinfection * Prevention achieved through good hygiene, safe sexual practices and avoiding sharing of intimate apparel * _Recommended regimen:_ * **Metronidazole** 2 gram orally single dose * Or * **Tinidazole** 2 gram orally single dose

Answer 54

* Members of the **nitroimidazole family** * **Nitro group** is _reduced in anaerobic bacteria and sensitive protozoans_ * Reactive products responsible for antimicrobial activity * The _only useful drugs_ for **trichomoniasis** * **No alcohol** for _24 hrs after metronidazole_ and _72 hrs after tinidazole_ * _Metronidazole AE:_ **nausea, headache, anorexia, and metallic taste** * Class B for pregnancy ⇒ no adverse events in animal studies * _Tinidazole_ has **fewer side effects** * Class C ⇒ some adverse events

Answer 55

* _Clinical manifestations_ * **Purulent vaginal discharge** * Usually has a **bad odor** * **Vulvar irritation** * _Risk factor_ * **Sexually transmitted** * _Physical exam_ * Purulent discharge; can be **yellow-green or frothy** * **Vulvar erythema** * _Vaginal pH_ * 4.5-6 * _Wet mount_ * Neutrophils * May see **motile trichomonads** * Can also do NAAT testing * _“Whiff test”_ * **May be ⊕** * _Treatment_ * Metronidazole (single or 7 day)

Answer 56

* Numerous species, most important is **C. albicans** * Long term fluconazole tx ⇒ appearance of other Candida species (especially **C. glabrata and C. krusei**) * _Candida albicans:_ * **Unicellular** ovoid organism * Adheres well to mucosal surfaces * Reproduces asexually by **budding** * Forms **pseudohyphae** ⇒ new budding cells → **filamentous elongated form** → true hyphae * Can also form sprout-like hyphae called **germ tubes** (in the presence of serum) → hyphae

Answer 57

* C. albicans are **nl flora of the** **mouth, intertriginous skin folds, GI tract and vagina** * Immunocompetent individuals have high resistance to Candida & other fungal infections * **Mucosal infections**, particularly of the **vagina** * Due to **disruptions in the normal flora** (abx use) ⇒ microbial imbalance ⇒ allows Candida to overgrow

Answer 58

* **Pruritis (burning and itching)** * **±** **Cheesy discharge** * Not a typical STD (endogenous transmission) * Often **recurrent** * More common in **3^rd trimester of pregnancy** and users of **estrogen contraceptives**

Answer 59

* Usually **clinical dx** * Confirmed by **microscopic exam of tissue** (w/ or w/o **KOH**) for _yeast and pseudohyphae_ * **Gram** **⊕**, size in between bacteria and host cell * C. albicans: **germ tube formation** in 1-2 hrs at _37__°__C in serum_, **chlamydospores** on _corn meal agar_

Answer 60

Eliminate predisposing factor(s) Topical antifungals

Answer 61

* _Clinical manifestations_ * **Vulvar pruritis/irritation** * May have **mild discharge** * _Risk factor_ * **Immune suppression, DM,** **↑** **estrogen, abx** * _Physical exam_ * **Vulvar erythema** * Thick, white, “**cottage-cheese**” like discharge * _Vaginal pH_ * **3.8-4.5** (normal) * _Wet mount_ * **Pseudohyphae** (also seen w/ KOH exam) * _“Whiff test”_ * **⊖** * _Treatment_ * Fluconazole or topical antifungal agents

Answer 62

* **Papovavirus** * Small **non-enveloped**, **isosohedral** capsid * **dsDNA** genome * ~70 types, classified into **16 groups** * Classified as **cutaneous** or **mucosal** HPV based on target tissues

Answer 63

* **Episomal genome** * **8 early genes:** E1 to E8 * Expression of E1 and E2 important for lytic cycle * Expression of E6 and E7 important for oncogenesis * **2 late or structural genes**: L1 and L2

Answer 64

* **Found worldwide, no seasonal incidence** * 20 million individuals in the US * **10-20% of women** may be infected * **HPV 16 and 18** directly linked to **cervical CA** * 2^nd leading cause of CA mortality in women

Answer 65

* _Requires close contact for transmission:_ * **Direct contact (breaks in skin)** * **Sexual contact** * **Passage through the birth canal** * ⊕ **Asymptomatic transmission** * **Capsid** confers environmental resistance * **Survives on inanimate objects** (**fomites**

Answer 66

* Enters via skin breaks * **Incubation 3-4 months** * _Lytic infection_ in a **permissive cell** * **Cutaneous** and **mucosal** forms * **Wart appearance** related to HPV type and site of infection * **Common, plantar and flat warts** ⇒ children and young adults * Resulting acquired immunity may limit disease in adults * **Genital warts** ⇒ sexually active individuals * Wart resolution in ~ 2 yrs * Viral persistence, asymptomatic shedding * _±_ _Oncogenic transformation_ of a **non-permissive cell** * Usu. by integrating viral genome into host genome * Some HPV types ass. w/ **oral and genital cancers**

Answer 67

_Viral replication linked to skin cell differentiation:_ * Infection of **basal cells** * _HPV early genes_ ⇒ **⊕** **host cell growth** & **viral genome replicatio**n using host DNA polymerase * Expression of **E1 and E2** important for lytic cycle * Cell division ⇒ **basal and prickle layer thickens** * **Basal layer differentiation** ⇒ ⊕ expression of nuclear factors ⇒ ⊕ transcription of viral proteins * **HPV late genes expression** in _terminally differentiated keratin layer_ * Assembled virion shed along w/ dead cells * **Warts** usu. **spontaneously regress** after months to years * **±** **Persistent or latent viral infections** in the basal layer * Virus remains in _plasmid form_

Answer 68

Strain specific (HPV 16, 18) * **Integration of viral genome into host DNA** ass. w/ **oncogenic events** * ~85% of cervical CA contain HPV DNA in integrated form * **Integration limits viral replication** (_inactivation of E1 and E2 genes_) * **Allows expression of viral oncogenes** (_E6 and E7_) * **E6 and E7** ⇒ ⊗ cellular growth suppressor proteins (**p53 and p105 or pRb**) * Uncontrolled cell proliferation * ↑ Susceptibility to mutations and other cancer-causing events

Answer 69

* Tobacco use * OCPs * Other STIs, chronic inflammation * Certain HLD-DR alleles

Answer 70

* Infection of **keratinized surfaces** * May result in **common, flat or plantar wart** * Depending on HPV type (**HPV 1-4, 10**) and site of infection * Usually results from infection in **childhood or adolescence**

Answer 71

* Occurs in **young children** or **adults \> 40 y/o** * In children, HPV acquired through birth canal * Ass. w/ **HPV 6, 11** * _Two types:_ * **Oral papillomas** ⇒ benign epithelial tumors in the oral cavity, * Usually solitary and rarely recur * **Laryngeal papillomas** ⇒ benign epithelial tumors of the larynx * Frequently recur

Answer 72

**“Condyloma acuminata”** * Occurs on **external genitalia and perianal areas** as a result of **sexual contact** * 90% are caused by **HPV 6 and 11** * Rarely become malignant (10%) * _Risk factors:_ * Sexual activity before 16 y/o * Multiple sexual partners * Partner w/ multiple sexual partners

Answer 73

**STI** of female genital tract w/ **HPV 16 or 18** ± Progressive cellular changes: dysplasia → neoplasia → carcinoma

Answer 74

* Virus **sequestered in skin cells** ⇒ limits exposure to immune system * **CMI** important for wart regression * _Persistent infection_ ass. w/ **transformation** * AIDS, lymphoproliferative d/o, immunosuppressive therapy ⇒ ↑ risk

Answer 75

* **Visual dx** by appearance * **Confirmed by PAP smear** * **Koilocytes** * Hyperplasia of prickle cells * Excessive production of keratin (hyperkeratosis) * **Molecular probes** and **PCR** * Used to ID virus in _cervical swabs and tissue specimens_ * HPV 16, 18

Answer 76

* **Dx cervical changes** by **Papanicolaou smears** * **Koilocytotic** squamous epithelial cells * Contain vacuolated cytoplasm and occur in rounded clumps

Answer 77

* **Warts** usually **spontaneously regress** but are **frequently surgically excised** * Removal ass. w/ high recurrence rate * **Papillomas** and **cervical dysplasia and neoplasia** must be **surgically removed** * _Pharmacologic agents:_ * Skin warts ⇒ salicylic acid * Anogenital warts ⇒ podophyllin, imiquimode (INF inducer) tricloracetic acid * Laryngeal warts ⇒ intralesion interferon * **Condoms** ↓ but cannot completely prevent sexual spread

Answer 78

* **Quadrivalent vaccine** * HPV 6, 11, 16, 18 * **Gardasil 9** * HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 * **3 shot series** * Targeted to adolescent girls * Recently approved and recommended for boys * Will not prevent all genital warts but provides significant (not complete) protection vs cervical cancer