# This Month in Vaginal Cancer Research **August 2026** --- Vaginal cancer accounts for only about 1 to 2% of gynecologic cancer diagnoses, and its research arrives in small increments rather than waves. August was a modest but genuinely useful month, and its center of gravity sat with prevention. A global modelling study put a number on something this community rarely sees quantified: how much vaginal cancer HPV vaccination could prevent in lower-income countries over the rest of the century, and the figure is in the millions. Alongside it, a systematic review examined why HPV vaccine uptake remains low in three European countries and found the obstacles center on knowledge and trust as much as on cost. On the treatment side, a German group reported how often two proteins that existing drugs target appear in primary vaginal cancer, and an Italian team reported outcomes for modern image-guided brachytherapy in vaginal relapse of endometrial and cervical cancer. A comprehensive review pulled together what is known about vaginal intraepithelial neoplasia after hysterectomy, including a recurrence figure that deserves both attention and careful reading. Rounding out the month, a case report made a point worth carrying: severe vulvovaginal scarring can make a cancer invisible to standard examination. *The papers highlighted here represent a selection of those published during the month. The papers were selected and summarized by AI. Accuracy of the summaries was confirmed by a scientist.* This digest incorporates only open-access research articles that are free to be read by the entire community and that are explicitly licensed to be shared and reused. --- **HPV vaccination is the clearest path to preventing vaginal cancer, and this month put numbers on it.** Most vaginal cancers are caused by persistent infection with high-risk types of human papillomavirus, the same virus behind most cervical cancer. Vaccination before exposure prevents that infection, and because vaginal cancer is rare, it almost never features in the argument for vaccination even though it stands to benefit. • HPV vaccination could prevent well over a million cases of vaginal cancer in lower-income countries this century, which is a scale of benefit this community almost never hears quantified. Researchers built a static cohort model covering 117 low- and middle-income countries from 2030 to 2100, using country-specific cancer mortality, HPV type distribution, population projections and vaccine coverage. Vaccination was projected to contribute to preventing about 1.27 million cases of vaginal cancer over that period (uncertainty range 1.20 to 1.45 million), the second largest of the four non-cervical cancers modelled after vulvar cancer at 2.18 million, with roughly 590,000 anal and 880,000 oropharyngeal cases also averted, and 3.02 million deaths across all four prevented by 2100. Africa was projected to see the largest relative reductions. Three things to hold alongside those figures. The model covers protection against HPV types 16 and 18 only, without cross-protection, so a nonavalent vaccine’s benefit would be larger. It assumes lifelong complete vaccine efficacy and leaves out herd immunity. And the authors themselves ask that the numbers be read as indications of relative magnitude and regional pattern rather than precise forecasts. Worth noting one internal inconsistency: the paper’s summary names Europe as gaining least, while its results section reports the Western Pacific region as consistently lowest. ([Read the full paper](https://doi.org/10.1136/bmjgh-2025-021127)) • Where HPV vaccination coverage stays low, the main obstacles are knowledge and trust, and that includes disagreement among clinicians themselves. This mixed-methods systematic review searched seven databases through April 2024 for studies on HPV vaccine uptake in Romania, Bulgaria and Croatia, three countries where coverage is rising but remains well below the 90% the World Health Organization recommends. From 31 studies the reviewers extracted 402 findings, grouped them into 65 categories, and combined those into 13 synthesized findings reported separately by country. Three patterns recurred across all three: attitudes shaped by distrust and misconception; gaps in knowledge, particularly about vaccinating boys as well as girls; and a lack of consensus among health professionals about how well the vaccine works and how safe it is, which affected both intention and uptake. That last finding is the uncomfortable one, because it locates part of the problem inside the health system rather than only in public attitudes. Cost and knowing where to get the vaccine were barriers too, in all three countries. Two limits on how far this generalizes: the evidence is dominated by Romania, with 20 of the 31 studies against three from Bulgaria, and most included studies predate recent policy changes that made the vaccine free. ([Read the full paper](https://doi.org/10.1136/bmjph-2025-003253)) *Check the citations section for a comprehensive list of publications associated with this topic.* --- **VaIN, the precancer of the vagina, comes back often enough that follow-up planning matters more than most people are told.** VaIN stands for vaginal intraepithelial neoplasia: abnormal cell changes in the lining of the vagina that can progress to cancer if left alone. It is much less common than its cervical equivalent and gets much less attention, which means women living with it often have less clear information about what to expect. • Among women treated for high-grade VaIN, recurrence at two to five years has been reported to reach 80%, and the review that reports it is careful about what that number does and does not mean. This review pulls together what is known about HPV-related vaginal wall lesions after hysterectomy, and its value is in the specifics. Start with the absolute risk, because the 80% is a recurrence figure and not a risk of developing VaIN in the first place: after hysterectomy for cervical precancer or cervical cancer, pooled data put the chance of developing any VaIN at about 2.7% and of vaginal cancer at roughly 0.3 per 1,000. VaIN itself accounts for under 1% of all lower genital tract precancerous lesions. The 80% applies to high-grade lesions (VaIN 2 to 3) after treatment, and the authors caution it is an upper-bound estimate pooled from studies that defined recurrence inconsistently, with much of it reflecting persistent HPV positivity rather than a confirmed lesion, in studies with high loss to follow-up. Low-grade VaIN is usually watched rather than treated and often regresses on its own. Risk factors listed include age, menopausal status, prior high-grade cervical precancer, high-risk HPV infection (HPV16 most consistently, with HPV18 and HPV31 also implicated), a suppressed immune system, positive surgical margins, smoking, multiple sexual partners and disturbance of the vaginal microbiome. Two practical points stand out. On examination, lesions hide at the vaginal apex, along the suture line and in the side fornices, so that is where a colposcopy should look hardest. On treatment, the review reports that for VaIN arising after hysterectomy for high-grade cervical precancer, current European consensus holds that laser and topical treatments are not preferred, because they cannot reach epithelium buried in surgical scar tissue, and that surgery should be prioritized; imiquimod, one of the topical options, is off-label for VaIN. The follow-up schedule it recommends is a first check at six months with both cytology and HPV testing, then every six months for two years, moving to annual testing after that if results stay clear. This is a narrative review, so the figures come from the literature it surveys rather than from new data. ([Read the full paper](https://doi.org/10.3389/fonc.2026.1897256)) *Check the citations section for a comprehensive list of publications associated with this topic.* --- **Treatment research this month came in two forms: making radiation more precise and counting how often known drug targets appear.** Because vaginal cancer is rare, there are no large, randomized trials to guide treatment, and much of what is known comes from single-center series and from laboratory work on stored tumor samples. • Modern image-guided internal radiation, added as a boost after external radiation, prevented any relapse at the treated site in this series, though everyone in it had a recurrence of a different cancer rather than primary vaginal cancer. Brachytherapy is internal radiation, where a radioactive source is placed inside or next to the tumor rather than aimed from outside the body; image guidance means the plan is shaped to what scans show at the time of treatment rather than to a standard template. Researchers in Rome retrospectively reviewed 32 consecutive patients, median age 54, treated between January 2019 and July 2025 for vaginal relapse of endometrial or cervical cancer after surgery, with 25 of the 32 (78%) relapsing at the vaginal vault. Nobody in this series had primary vaginal cancer, so the results do not transfer directly to that diagnosis. Treatment was a median 45 Gy of external beam radiation, with concurrent weekly cisplatin in 24 of the 32, followed by an endovaginal boost of a median 28 Gy over four to six high-dose-rate sessions. No patient relapsed at the treated site during follow-up, giving a projected two-year local control of 100%, with projected metastasis-free survival 77.8% and both overall and cancer-specific survival 93%. Median follow-up was only 17 months, so those two-year figures are actuarial estimates rather than two years of observation in most patients, and the authors name limited follow-up and small sample size as their main limitations. Serious side effects were uncommon but real: two patients had moderate short-term bowel or skin effects, and at 15 months one patient developed severe vaginal narrowing and another an opening between the rectum and vagina. Patients who also received chemotherapy had fewer distant metastases on single-variable analysis, but that did not translate into better survival, and on multivariable analysis age was the only independent predictor of mortality. ([Read the full paper](https://doi.org/10.1007/s11547-026-02235-8)) • Two proteins that existing drugs are built to attack turn up often in primary vaginal cancer, which sharpens a testing conversation that guidelines already recommend having. Researchers at University Medical Center Mainz retrospectively examined stored tumor samples from 34 people with primary vaginal cancer, with linked clinical outcomes, for four proteins: p16 and p53, which are markers of how the cancer arose, and HER2 and Nectin-4, both of which are targets of drugs already approved in other cancers. HER2 was positive in 14.7% of tumors. Nectin-4 was far more common, with some expression in roughly 82% of cases and strong overall expression in 20.59%. HER2 positivity was associated with adenocarcinoma histology, p16-negative status and younger age, and p16-negative status also went with adenocarcinoma, but these associations rest on just four adenocarcinomas in the whole series: the confidence intervals are very wide and the age association was only marginally significant. Neither p16 nor p53 predicted outcome, and neither HER2 nor Nectin-4 expression was linked to how patients did, which the authors attribute in part to having only 10 deaths and therefore very little statistical power. This is a retrospective single-center study of 34 archived samples that the authors describe as exploratory, so it establishes prevalence rather than showing that drugs against these targets work in vaginal cancer. The reason it still matters at the bedside is that current NCCN guidance already recommends HER2 and PD-L1 testing for advanced, recurrent or metastatic vaginal cancer, and trastuzumab deruxtecan carries a tumor-agnostic approval for HER2-high solid tumors, so knowing these markers are present at these rates is an argument for making sure that testing actually happens. ([Read the full paper](https://doi.org/10.3390/ijms27157018)) *Check the citations section for a comprehensive list of publications associated with this topic.* --- **Severe vulvovaginal scarring can hide a cancer, and standard examination will miss it.** Lichen sclerosus and lichen planus are long-term inflammatory skin conditions that affect the vulva and vagina. Left untreated they can scar tissue progressively, and this month’s case report shows where that can lead. • When scarring has closed the vagina, the usual examinations become impossible, and this case shows what it takes to get to a diagnosis anyway. Doctors in Lucerne, Switzerland describe an elderly postmenopausal woman with untreated overlapping vulvar lichen sclerosus and lichen planus who came in with abdominal pain, constipation and urinary symptoms. Severe vulvovaginal scarring had completely closed her vagina, which made both speculum examination and transvaginal ultrasound impossible; scanning through the abdomen was limited by bowel gas and discomfort, and it was ultrasound through the rectum that found a 12 cm fluid-filled pelvic mass. MRI or CT was considered but urgent surgery was prioritized, because her pain, constipation and obstruction were unlikely to be changed by more imaging. At surgery about 900 mL of old blood and fluid had collected above the closed-off vagina, distending the vagina itself, which was the mass seen on the scan, with the uterus enlarged and pushed upwards. She had a hysterectomy, removal of the tubes and ovaries, and partial removal of the vagina. The tissue showed a FIGO stage IIB, grade 2 endometrioid endometrial cancer classed as high-intermediate risk with mismatch repair deficiency, while the vaginal tissue itself was benign scar; genetic testing ruled out Lynch syndrome, the inherited condition that mismatch repair deficiency can point to, and lymph nodes were not assessed because of her frailty. She then had pelvic radiotherapy for the cancer and long-term potent topical steroids and emollients for her vulvar disease, and remained free of recurrence at 24 months, at which point follow-up stopped as her dementia progressed. This is one patient, so it illustrates a possibility rather than establishing how often this happens. The transferable point is twofold: untreated lichen sclerosus and lichen planus can scar to the point of obstruction, which is a reason to treat them rather than live with them, and when examination is blocked, an alternative route to the diagnosis has to be found rather than assumed unavailable. ([Read the full paper](https://doi.org/10.1136/bcr-2026-272712)) *Check the citations section for a comprehensive list of publications associated with this topic.* --- **Epidemiology, access, and health disparities research.** Where a woman lives shapes her odds after a diagnosis of any female cancer, and vaginal cancer, being rare and under-served, is unusually exposed to that. • Among young women worldwide, the countries with the highest rates of female cancers are not the countries where women are most likely to die of them, and vaginal cancer is projected to be among the fastest-rising in mortality. Researchers used GLOBOCAN 2022 estimates to quantify the burden of six female cancers, including vaginal cancer, among adolescent and young adult women aged 15 to 39 across 185 countries, then projected forward to 2050. In 2022 there were an estimated 406,385 new cases and 93,848 deaths in this age group across all six cancers, of which vaginal cancer accounted for 1,171 cases and 366 deaths. Breast cancer carried the largest share of both, and cervical cancer the worst ratio of deaths to diagnoses. The inequity is in the pattern: very high development index countries had the highest incidence but the lowest mortality, while low development index countries had disproportionately high mortality and the worst death-to-diagnosis ratio, with development level strongly inversely associated with mortality. Assuming rates stay as they are, cases across all six cancers are projected to rise 13.7% and deaths 27.7% globally by 2050, with the largest increases in Africa and in low development index countries. The detail most relevant here is that vaginal and vulvar cancers are projected to show the largest relative mortality increases of the six, at roughly 30% and 62% respectively. Two caveats travel with all of this: these are modelled estimates rather than counted cases, and the projections assume 2022 rates hold constant, which the authors describe as a reference scenario rather than a true forecast. ([Read the full paper](https://doi.org/10.3389/fonc.2026.1896950)) *Check the citations section for a comprehensive list of publications associated with this topic.* --- ## What Does This Mean for Me? **I have been treated for VaIN. What should I expect now?** Expect to need long-term follow-up, and expect that to be the normal course rather than a sign something has gone wrong. The review published this month reports cumulative recurrence after treatment for high-grade VaIN reaching up to 80% at two to five years. Read that number carefully, because the authors do: it is an upper-bound estimate pooled from studies that defined recurrence differently, and a substantial share of it reflects a persistent HPV infection rather than a confirmed lesion. If your VaIN was low grade, it is usually watched rather than treated and often clears by itself, and the 80% does not describe your situation. The follow-up schedule the review recommends is worth taking to your team: a first check at six months with both cytology and HPV testing, then every six months for two years, and annually after that if results stay clear. Two other things from the same review are worth raising. Lesions tend to hide at the top of the vagina, along the surgical suture line and in the side pockets, so it is fair to ask whether your colposcopy examines those areas specifically. And if your hysterectomy was for high-grade cervical precancer, the review notes that European consensus favors surgical treatment over laser or topical creams for VaIN in that situation, because those treatments cannot reach cells buried in scar tissue. If a topical or laser option has been proposed to you, that is a reasonable thing to ask about. **Is there any targeted treatment for vaginal cancer?** There is more of a conversation to be had than most people realize. Vaginal cancer is rare enough that no large trials have been run in it, and treatment is generally adapted from cervical and vulvar cancer. But current NCCN guidance already recommends testing for HER2 and PD-L1 in advanced, recurrent or metastatic vaginal cancer, and there is a tumor-agnostic approval for trastuzumab deruxtecan in HER2-high solid tumors, which a vaginal cancer with high HER2 could fall under. What this month’s study adds is how often those markers actually appear: in 34 archived tumor samples, HER2 was positive in about 15% and Nectin-4 showed some expression in roughly 82%. That study is exploratory laboratory work on stored samples and does not show that drugs against these targets work here. The practical question it supports is simply whether the recommended testing has been done in your case, and if not, why not. **My mother or I have lichen sclerosus that has never really been treated. Does it matter?** It can matter a great deal, and the case published this month is a reason to take it seriously rather than a reason to be alarmed. Lichen sclerosus and lichen planus are treatable long-term skin conditions, usually with potent topical steroids, and treated they are generally well controlled. Untreated over years they can scar progressively, and in this case the scarring had closed the vagina completely, which caused an obstruction and made it impossible to examine or scan through the vagina to find the cancer that had developed behind it. The diagnosis was eventually reached by scanning through the rectum, and then by going to surgery rather than waiting for more imaging. Two things worth doing: if the condition is not currently being treated, ask why not, and if there are new symptoms that cannot be examined in the usual way, ask specifically what alternative route to a diagnosis is available rather than accepting that nothing can be seen. *This digest is prepared by OCRA (Ovarian Cancer Research Alliance) for patients, caregivers, and advocates. It is intended to inform, not to guide individual treatment decisions. Please speak with your care team about what research findings may mean for your specific situation.* --- ## Sources *Citations are grouped by the topic sections above. Within each section, the papers directly referenced in the digest are listed first, followed by additional on-topic papers published this month that are either not discussed above or are behind access restrictions.* **HPV vaccination is the clearest path to preventing vaginal cancer, and this month put numbers on it.** ***Directly referenced:*** 1\. Tuli A et al.. “Projections of human papillomavirus (HPV) vaccination impact on non-cervical cancer outcomes among women in 117 low- and middle-income countries: a modelling study.” *BMJ Glob Health.* August 31, 2026. PMID 42674727. 2\. Bennett C et al.. “What are the barriers and enablers to the uptake of the HPV vaccine in Romania, Bulgaria and Croatia? A mixed methods systematic review.” *BMJ Public Health.* August 25, 2026. PMID 42689009. **VaIN, the precancer of the vagina, comes back often enough that follow-up planning matters more than most people are told.** ***Directly referenced:*** 3\. Zhang D et al.. “Research progress on HPV-related vaginal wall lesions after hysterectomy.” *Front Oncol.* August 20, 2026. PMID 42694624. ***Additional citations on related topics:*** 4\. Indraccolo U et al.. “The Progression of Vaginal Intraepithelial Neoplasia to Cancer: A Systematic Review and Meta-Analysis.” *J Womens Health (Larchmt).* August 2026. PMID 41943441. *(subscription access)* 5\. Chen J et al.. “HPV Genotype Distribution and Its Anatomical Site Specificity in Vaginal Intraepithelial Neoplasia.” *J Med Virol.* August ??, 2026. PMID 42555146. *(subscription access)* 6\. Xiong J et al.. “The detection trends of vaginal intraepithelial neoplasia (VaIN) by colposcopic from 2020-2023 and analysis of clinical efficacy of photodynamic and carbondioxide laser in VaIN.” *Photodiagnosis Photodyn Ther.* August 12, 2026. PMID 42586289. *(restricted license, CC BY-NC-ND 4.0)* **Treatment research this month came in two forms: making radiation more precise and counting how often known drug targets appear.** ***Directly referenced:*** 7\. Lancellotta V et al.. “Image-guided adaptive interventional radiotherapy (modern brachytherapy) boost for vaginal recurrences.” *Radiol Med.* August 2026. PMID 42322514. 8\. Klamminger GG et al.. “Evaluation of HER2 and Nectin-4 Expression in Primary Vaginal Cancers.” *Int J Mol Sci.* August 5, 2026. PMID 42589670. ***Additional citations on related topics:*** 9\. Xu J. “Laparoscopic Resection of Vaginal Embryonal Rhabdomyosarcoma in a 16-Month-Old Girl: An Organ-Preserving Surgical Approach.” *J Pediatr Adolesc Gynecol.* August 2026. PMID 41866106. *(license unconfirmed)* 10\. Marshall EH et al.. ““Fibrosarcoma-like” Tumors of the Gynecologic Tract Show Distinct Molecular Subgroups: Tyrosine Kinase Fusions and Recurrent ERBB2/3 Mutations.” *Mod Pathol.* August 27, 2026. PMID 42660426. *(license unconfirmed)* **Severe vulvovaginal scarring can hide a cancer, and standard examination will miss it.** ***Directly referenced:*** 11\. Vaz I et al.. “Hidden endometrial cancer due to vaginal obliteration associated with lichen sclerosus/lichen planus.” *BMJ Case Rep.* August 18, 2026. PMID 42613127. **Epidemiology, access, and health disparities research.** ***Directly referenced:*** 12\. Ding R et al.. “Female cancers in adolescent and young adult women: global inequities and 2050 burden estimates from GLOBOCAN 2022.” *Front Oncol.* August 6, 2026. PMID 42625591. --- # This Month in Vulvar Cancer Research **August 2026** --- Vulvar cancer is rare, accounting for roughly 5% of gynecologic cancer diagnoses, and that rarity shapes the research: fewer large trials, more single-center series and case reports, and steady incremental work rather than dramatic breakthroughs. August’s research reflected that character, with its strongest thread running through precancerous conditions and the two distinct biological routes to vulvar cancer, one driven by HPV infection and one arising in chronically inflamed skin such as lichen sclerosus. Alongside that came a first clinical report of a new drug approach for treatment-resistant lichen sclerosus, a global modelling study putting numbers on how much vulvar cancer HPV vaccination could prevent, practical work on making daily radiation treatment more accurate, and a striking case of advanced vulvar Paget’s disease that responded completely to chemoradiation. Laboratory research on a new way to make chemotherapy more effective rounded out the month. Nothing published in August changes standard practice on its own, but several papers point at where practice may go. *The papers highlighted here represent a selection of those published during the month. The papers were selected and summarized by AI. Accuracy of the summaries was confirmed by a scientist.* This digest incorporates only open-access research articles that are free to be read by the entire community and that are explicitly licensed to be shared and reused. --- **Vulvar cancer has two separate origins, and they need separate management.** Most vulvar cancers arise along one of two routes. One begins with persistent HPV infection and produces high-grade squamous intraepithelial lesions, also called vulvar intraepithelial neoplasia or VIN, meaning precancerous cell changes in the surface layer of the vulva. The other is HPV-independent and arises in skin already altered by chronic inflammatory conditions, above all lichen sclerosus, a long-term skin condition that thins and scars vulvar tissue and, over years, raises the risk of vulvar cancer. Which route your condition follows changes what treatment makes sense, and confusing the two is a real clinical risk. • A drug long used for other inflammatory conditions is being tried for lichen sclerosus that has stopped responding to standard treatment, with the aim of keeping precancer from coming back. A Dutch clinical team reports its first experience giving low-dose methotrexate to people with therapy-resistant lichen sclerosus who also had HPV-independent VIN, and describes an extension of the interval before the precancerous changes recurred. This is a first clinical report rather than a trial, so it establishes that the approach is worth studying, not that it works: how many people were treated, how long the benefit lasted, and how it compares with continued standard care are the questions a proper study will need to answer. Worth knowing about if you are living with lichen sclerosus that potent topical steroids are no longer controlling. ([Read the full paper](https://doi.org/10.1093/bjd/ljag364)) *Check the citations section for a comprehensive list of publications associated with this topic.* --- **HPV vaccination could prevent more vulvar cancer than any other single measure, and vulvar cancer turns out to be the biggest share of the benefit outside the cervix.** Vaccination campaigns have been justified almost entirely on preventing cervical cancer. This month’s modelling work asked what else those same vaccines would prevent. • Of all the non-cervical cancers HPV vaccination could prevent in women, vulvar cancer is projected to be the largest, which is a strong argument for vaccination that patients and advocates rarely hear made. Researchers built a model covering 117 low- and middle-income countries from 2030 to 2100, using country-specific cancer mortality, HPV type distribution, population projections and vaccine coverage. Bivalent HPV vaccination was projected to contribute to preventing about 2.18 million cases of vulvar cancer over that period, more than the projected 1.27 million vaginal, 880,000 oropharyngeal and roughly 590,000 anal cancer cases, with 3.02 million deaths across all four averted by 2100. The largest relative reductions were projected for the African region and the smallest for the European region. This is a modelling study, so the figures are projections built on current data rather than observed results, and they apply only to the HPV-driven route to vulvar cancer, not the lichen sclerosus route. ([Read the full paper](https://doi.org/10.1136/bmjgh-2025-021127)) *Check the citations section for a comprehensive list of publications associated with this topic.* --- **Getting radiation to land in the same place every day is harder for vulvar cancer than for most cancers, and technology is starting to help.** Radiation for vulvar cancer is often delivered in the “frog-leg” position, with the legs apart and rotated outward, to spare the skin from the worst of the treatment. It works for skin toxicity but it is an unstable position to reproduce day after day. • A camera-based system that tracks the surface of your body may position you considerably more accurately for vulvar radiation than the skin ink marks traditionally used. In a retrospective comparison of 20 people treated in the frog-leg position, half positioned with conventional laser and skin-mark alignment and half with surface-guided radiotherapy, researchers analyzed 500 daily CT datasets. Rotational tilt error fell from 1.21 degrees to 0.07 degrees and lengthwise positioning error from about 5 mm to under 1 mm. Body mass index was strongly correlated with rotational error in the conventionally positioned group but showed no statistically significant correlation in the surface-guided group, which the authors read as the system removing a source of setup uncertainty tied to body habitus. With ten people per group, that comparison is a weak test rather than proof of no effect, and the study measures positioning accuracy rather than whether patients ultimately do better, though more accurate setup is what allows treatment margins to be safely narrowed. ([Read the full paper](https://doi.org/10.1002/acm2.70714)) *Check the citations section for a comprehensive list of publications associated with this topic.* --- **The rarest vulvar cancers are where single well-documented cases still change what doctors think is possible.** Vulvar Paget’s disease, melanoma, adenocarcinoma and the mesenchymal tumors are each rare enough that no trial will ever be run in them, so the evidence base is built case by case. • Even vulvar Paget’s disease that has spread to lymph nodes far from the pelvis may respond completely to chemoradiation, which matters because such spread has generally been treated as a sign that cure is out of reach. Doctors in Korea describe a 70-year-old woman with invasive vulvar extramammary Paget’s disease, a rare adenocarcinoma of the skin that can arise on the vulva, whose disease involved lymph nodes in the groin, pelvis, along the aorta and up into the left supraclavicular region above the collarbone. She received definitive concurrent chemoradiotherapy with weekly cisplatin, treating the groin-to-para-aortic nodes with 57.6 Gy in 32 fractions and the supraclavicular nodes with 51.0 Gy in 17 fractions. Imaging six months after treatment showed a complete response. This is one patient with six months of follow-up, so it shows what is possible rather than what to expect, but for a situation usually approached palliatively that is a meaningful data point. ([Read the full paper](https://doi.org/10.3857/roj.2026.00388)) *Check the citations section for a comprehensive list of publications associated with this topic.* --- **Vulvar cancer is becoming more common, and in some parts of the world it is rising fast.** Understanding who is developing vulvar cancer, and where, is what drives decisions about screening, vaccination and where to put resources. • Vulvar cancer incidence in Harare, Zimbabwe rose 5.6% per year over three decades, the steepest increase among the five women’s cancers tracked there. Researchers analyzed cancer registry data for the Black African female population of Harare from 1990 to 2019, following breast, cervical, uterine, ovarian and vulvar cancers. Vulvar cancer incidence is relatively high there by global standards, and the authors note that the elevated burden of both cervical and vulvar cancer fits the pattern seen in populations with high HPV prevalence, while cautioning that population-specific HPV data remain limited. Over the same period ovarian cancer incidence held steady and breast cancer rose 3% annually, mainly in women over 40. Registry data describe what is happening rather than why, but a rise this steep in a preventable, HPV-associated cancer is a prevention story. ([Read the full paper](https://doi.org/10.1002/ijc.70436)) *Check the citations section for a comprehensive list of publications associated with this topic.* --- **General and basic-science vulvar cancer research.** This is early laboratory work, several steps away from anyone’s treatment, but it is where the next options come from. • A physical treatment that floods cells with reactive oxygen and nitrogen may make cisplatin work better against vulvar cancer, and the order it is given in seems to matter. Working in vulvar squamous cell carcinoma cells, researchers in Germany tested two forms of low-temperature argon plasma, a liquid solution and a hydrogel, alone and in sequence with cisplatin. The solution produced a rapid burst of reactive molecules while the hydrogel released them slowly and steadily; both reduced cell survival on their own, and giving the plasma treatment before cisplatin rather than after produced the higher synergy, with laboratory markers pointing to oxidative stress and programmed cell death as the mechanism. This is cell-culture work in carcinoma cells, with no patients and no animals involved, so its value is in identifying a direction worth testing. The authors also raise precancerous lesions as a possible future application, naming both routes’ precursors, HSIL on the HPV-driven side and differentiated VIN on the HPV-independent side, but no precancerous lesion was tested here. ([Read the full paper](https://doi.org/10.32604/or.2026.081755)) *Check the citations section for a comprehensive list of publications associated with this topic.* --- ## What Does This Mean for Me? **I have lichen sclerosus. Does any of this change what I should be doing?** Not yet, but it is worth knowing that the search for better options is active. Lichen sclerosus is managed long term with potent topical steroids, and for most people that controls it. This month’s report describes low-dose methotrexate as a first clinical experience in people whose lichen sclerosus had stopped responding and who had also developed HPV-independent VIN. If that describes you, it is reasonable to ask your specialist whether they are aware of this work and whether any trial is recruiting. The more important standing point is that lichen sclerosus warrants ongoing specialist follow-up rather than occasional prescription refills, because the precancerous changes that can develop in it are found by someone examining the tissue, not by symptoms alone. A useful question for your care team: how often should I be examined, and what changes should bring me in sooner? **Will the HPV vaccine protect me or my daughter from vulvar cancer?** For the HPV-driven route to vulvar cancer, the modelling published this month suggests the answer is a substantial yes, and that vulvar cancer is the largest single share of the vaccine’s benefit outside the cervix. That is a genuine argument for vaccination that rarely gets made. Two honest limits: these are projections from a model rather than observed outcomes, and the vaccine addresses only the HPV-associated pathway. If your vulvar cancer or precancer arose from lichen sclerosus rather than HPV, vaccination is not the relevant prevention strategy for you, and continued skin surveillance is. **I am about to start radiation for vulvar cancer. Is there anything worth asking about?** You will likely be positioned in the frog-leg posture, which is uncomfortable and hard to reproduce exactly day to day. The study this month found that a camera-based surface-guidance system positioned people considerably more accurately than skin ink marks and lasers, and that in the conventionally positioned group body size was strongly related to how much the pelvis rotated out of position. Not every center has this equipment, the comparison involved only ten people per group, and better positioning has not yet been shown to translate into better outcomes or fewer side effects. Still, it is fair to ask what your center uses for daily positioning and how they check it, particularly if you have found the position difficult to hold. *This digest is prepared by OCRA (Ovarian Cancer Research Alliance) for patients, caregivers, and advocates. It is intended to inform, not to guide individual treatment decisions. Please speak with your care team about what research findings may mean for your specific situation.* --- ## Sources *Citations are grouped by the topic sections above. Within each section, the papers directly referenced in the digest are listed first, followed by additional on-topic papers published this month that are either not discussed above or are behind access restrictions.* **Vulvar cancer has two separate origins, and they need separate management.** ***Directly referenced:*** 1\. Wouters D, et al. “Low-dose methotrexate in therapy-resistant lichen sclerosus: first clinical experience with recurrence-free interval extension in HPV-independent vulvar intraepithelial neoplasia (HPVi VIN).” *Br J Dermatol.* August 28, 2026. PMID 42663040. ***Additional citations on related topics:*** 2\. Welch KC, et al. “Precancerous Squamous Lesions of the Vulva.” *Obstet Gynecol.* August 2026. PMID 41380160. *(subscription access)* 3\. Zhang G, et al. “Papillary Squamous Intraepithelial Lesion Outside the Uterine Cervix: Clinicopathological Characterization and Immunohistochemical Study.” *Am J Surg Pathol.* August 2026. PMID 42060367. *(subscription access)* **HPV vaccination could prevent more vulvar cancer than any other single measure, and vulvar cancer turns out to be the biggest share of the benefit outside the cervix.** ***Directly referenced:*** 4\. Tuli A, et al. “Projections of human papillomavirus (HPV) vaccination impact on non-cervical cancer outcomes among women in 117 low- and middle-income countries: a modelling study.” *BMJ Glob Health.* August 31, 2026. PMID 42674727. **Getting radiation to land in the same place every day is harder for vulvar cancer than for most cancers, and technology is starting to help.** ***Directly referenced:*** 5\. Liang H, et al. “Surface-Guided Radiotherapy for Vulvar Cancer in the Frog-Leg Position: Setup Accuracy and BMI Effects.” *J Appl Clin Med Phys.* August 2026. PMID 42503572. ***Additional citations on related topics:*** 6\. Titone F, et al. “Optimizing the multidisciplinary management of vulvar and vaginal cancers: A position paper from Italian experts.” *Crit Rev Oncol Hematol.* August 12, 2026. PMID 42586399. *(subscription access)* **The rarest vulvar cancers are where single well-documented cases still change what doctors think is possible.** ***Directly referenced:*** 7\. Park S, et al. “Concurrent chemoradiotherapy for metastatic vulvar extramammary Paget’s disease involving supraclavicular nodes: a case report.” *Radiat Oncol J.* August 10, 2026. PMID 42634497. ***Additional citations on related topics:*** 8\. Soni P, et al. “MEIS1::NCOA2 Rearranged Spindle Cell Neoplasm of Vulva With Unusual Low-Grade Morphology.” *Genes Chromosomes Cancer.* August 2026. PMID 42629629. *(restricted license, CC BY-NC-ND)* **Vulvar cancer is becoming more common, and in some parts of the world it is rising fast.** ***Directly referenced:*** 9\. Chokunonga E, et al. “Trends in the incidence of cancers of the breast and female genital tract in Harare, Zimbabwe 1990-2019.” *Int J Cancer.* August 2026. PMID 41803021. ***Additional citations on related topics:*** 10\. Tran HTT, et al. “Patterns of excess and cause-specific mortality in vulvar squamous cell carcinoma: a Surveillance, Epidemiology, and End Results program population-based study.” *Int J Gynecol Cancer.* August 2026. PMID 42349066. *(subscription access)* **General and basic-science vulvar cancer research.** ***Directly referenced:*** 11\. Schad ECID, et al. “Combinatorial Effects of Plasma-Treated Solution and Plasma-Treated Hydrogel with Cisplatin in Vulvar Cancer Cells.” *Oncol Res.* August 13, 2026. PMID 42630708. ***Additional citations on related topics:*** 12\. Julakanti P, et al. “A Heterogeneous Phenotypic Presentation of a PALB2 Mutation Carrier With Multiple Metachronous Primary Malignancies: A Case Report.” *Cureus.* August 31, 2026. PMID 42689189. *(open access: an inherited PALB2 mutation identified in a woman with several separate primary cancers including a vulvar cancer, with the authors noting the PALB2 link to vulvar cancer is not established)* --- *A note on how this digest was made: This edition was built by searching PubMed for papers published in August 2026, using targeted searches across the vulvar cancer landscape (sentinel lymph node and groin management, surgery and morbidity, radiation and chemoradiation, lichen sclerosus and VIN/dVIN/HSIL, HPV prevention, rare subtypes, immunotherapy, biomarkers, survivorship, disparities) plus a dedicated qualitative search. Papers summarized in full are open-access under a permitted license (CC0, CC BY, CC BY-SA, CC BY-ND, or CC BY-NC); on-topic papers under other licenses are listed by citation only. A companion methodology report, available separately, documents the full search-and-screening process and every paper reviewed.*

This Month in Vaginal & Vulvar Cancer Research

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